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BACKGROUND AND PURPOSE: Prostate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer. EXPERIMENTAL APPROACH: NL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses. KEY RESULTS: Compared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC50, 3.51 µM vs. 35.45 µM) and DU145 (IC50, 2.53 µM vs. 29.35 µM) prostate cancer cells viability and PLK4 kinase activity (2.32 µM vs. 246.88 µM). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down-regulation and triggered apoptosis via caspase-9/caspase-3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p-AKT and increased cleaved caspase-9/3. CONCLUSION AND IMPLICATIONS: NL13, a novel PLK4-targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4-AKT-CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy.
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Conventional tumor diagnosis and treatment approaches have significant limitations in clinical application, whereas personalized theranostistic nanoplatforms can ensure advanced diagnosis, precise treatment, and even a good prognosis in cancer. Tumor microenvironment (TME)-targeted therapeutic strategies offer absolute advantages in all aspects compared to tumor cell-targeted therapeutic strategies. It is essential to create a TME-responsive all-in-one nanotheranostic platform to facilitate individualized tumor treatment. Based on the TME-responsive multifunctional nanotheranostic platform, we focus on the combined use of multimodal imaging and therapeutic protocols and summary and outlooks on the latest advanced nanomaterials and structures for creating the integrated nanotheranostic system based on material science, which provide insights and reflections on the development of innovative TME-targeting tools for cancer theranostics.
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Imagen Multimodal , Neoplasias , Nanomedicina Teranóstica , Microambiente Tumoral , Humanos , Imagen Multimodal/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Nanomedicina Teranóstica/métodos , Animales , Nanoestructuras , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Angiogenesis inhibitors and photosensitizers are pivotal in tumor clinical treatment, yet their utilization is constrained. Herein, eleven novel angiogenesis inhibitors were developed through hybridization strategy to overcome their clinical limitations. These title compounds boast excitation wavelengths within the "therapeutic window", enabling deep tissue penetration. Notably, they could generate superoxide anion radicals via the Type I mechanism, with compound 36 showed the strongest superoxide anion radical generating capacity. Biological evaluation demonstrated remarkable cellular activity of all the title compounds, even under hypoxic conditions. Among them, compound 36 stood out for its superior anti-proliferative activity in both normoxic and hypoxic environments, surpassing individual angiogenesis inhibitors and photosensitizers. Compound 36 induced cell apoptosis via superoxide anion radical generation, devoid of dark toxicity. Molecular docking revealed that the target-recognizing portion of compound 36 was able to insert into the ATP binding pocket of the target protein similar to sorafenib. Collectively, our results suggested that hybridization of angiogenesis inhibitors and photosensitizers was a potential strategy to address the limitations of their clinical use.
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Inhibidores de la Angiogénesis , Proliferación Celular , Simulación del Acoplamiento Molecular , Fármacos Fotosensibilizantes , Superóxidos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Humanos , Superóxidos/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/síntesis química , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacosRESUMEN
Ovomucin-Complex extracted from egg white is expected to have a barrier function similar to gastric mucin. In this study, the dynamic changes in structure, rheological properties and binding ability of Ovomucin-Complex during in vitro simulated gastric digestion were investigated. The results from HPLC and CLSM showed that extremely acidic pH (pH = 2.0) promoted Ovomucin-Complex to form aggregation. Acid-induced aggregation may hinder its binding to pepsin, thus rendering Ovomucin-Complex resistant to pepsin. Consequently, most of the polymer structure and weak gel properties of Ovomucin-Complex retained after simulated gastric digestion as verified by HPLC, CLSM and rheological measurement, although there was a small breakdown of the glycosidic bond as confirmed by the increased content of reducing sugar. The significantly reduced hydrophobic interactions of Ovomucin-Complex were observed under extremely acidic conditions and simulated gastric digestion compared with the native. Noticeably, the undigested Ovomucin-Complex after simulated gastric digestion showed a higher affinity (KD = 5.0 ± 3.2 nm) for urease - the key surface antigen of Helicobacter pylori. The interaction mechanism between Ovomucin-Complex and urease during gastric digestion deserves further studies. This finding provides a new insight to develop an artificial physical mucus barrier to reduce Helicobacter pylori infection.
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Digestión , Ovomucina , Ureasa , Ureasa/metabolismo , Ureasa/química , Ovomucina/química , Ovomucina/metabolismo , Concentración de Iones de Hidrógeno , Unión Proteica , Pepsina A/metabolismo , Pepsina A/química , Polimerizacion , Helicobacter pylori , Reología , HumanosRESUMEN
Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28 days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48 days; 26 days for hypoxic/ischemic injury and 43 days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: ⢠Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. ⢠Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. ⢠There are no reliable biochemical markers to predict the outcome of NALF. What is New: ⢠In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. ⢠The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.
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Fallo Hepático Agudo , Humanos , Estudios Retrospectivos , China/epidemiología , Femenino , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/epidemiología , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/diagnóstico , Masculino , Recién Nacido , Pronóstico , Estimación de Kaplan-MeierRESUMEN
AIM: Achondroplasia is the most common of the skeletal dysplasias that cause fatal and disabling growth and developmental disorders in children, and is caused by a mutation in the fibroblast growth factor receptor, type 3 gene(FGFR3). This study aims to analyse the clinical characteristics and gene mutations of ACH to accurately determine whether a patient has ACH and to raise public awareness of the disease. METHODS: The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of "Achondroplasias" or "Skeleton-Skin-Brain Syndrome" or "Skeleton Skin Brain Syndrome" or "ACH" and "Receptor, Fibroblast Growth Factor, Type 3" or "FGFR3". RESULTS: Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31-53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970_971insTCTCCT. CONCLUSION: ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum.
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Acondroplasia , Genu Valgum , Megalencefalia , Osteocondrodisplasias , Niño , Recién Nacido , Adolescente , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Acondroplasia/genética , Acondroplasia/patología , Mutación/genéticaRESUMEN
Dairy products are susceptible to modifications in protein oxidation during heat processing, which can lead to changes in protein function, subsequently affecting intestinal health. Despite being a unique nutritional source, yak milk has not been thoroughly examined for the effects of its oxidized proteins on intestinal microbiota and metabolism. Hence, this study employed different heat treatment methods (low-temperature pasteurization, high-temperature pasteurization, and high-temperature sterilization) to induce oxidation in yak milk proteins. The study then assessed the degree of oxidation in these proteins and utilized mice as research subjects. Using metagenomics and metabolomics methods, this study examined the structure of intestinal microbial communities and metabolic products in mice consuming oxidized yak milk. The results showed a decrease in carbonyl and total thiol contents of yak milk proteins after different heat treatments, indicating that heat treatment causes oxidation in yak milk proteins. Metagenomic analysis of mouse intestinal microbiota revealed significant changes in 66 genera. In the high-temperature sterilization group (H), key differential genera included Verrucomicrobiales, Verrucomicrobiae, Akkermansiaceae, and 28 others. The high-temperature pasteurization group (M) mainly consisted of Latilactobacillus, Bacillus, and Romboutsia. The low-temperature pasteurization group (L) primarily comprised of Faecalibacterium, Chaetomium, Paenibacillaceae, Eggerthella, Sordariales, and 33 others. Functionally, compared to the control group (C), the H group upregulated translation and energy metabolism functions, the L group the M group significantly upregulated metabolism of other amino acids, translation, and cell replication and repair functions. Based on metabolomic analysis, differential changes in mouse metabolites could affect multiple metabolic pathways in the body. The most significantly affected metabolic pathways were phenylalanine metabolism, vitamin B6 metabolism, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. The changes were similar to the functional pathway analysis of mouse metagenomics, affecting amino acid and energy metabolism in mice. In summary, moderate oxidation of yak milk proteins exhibits a positive effect on mouse intestinal microbiota and metabolism. In conclusion, yak milk has a positive effect on mouse intestinal microflora and metabolism, and this study provides a scientific basis for optimizing dairy processing technology and further developing and applying yak milk.
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Objective: The relationship between serum selenium levels and papillary thyroid cancer (PTC), especially the pathological features, still remains controversial. We conducted this study to investigate the relationship between serum selenium levels and PTC in a Chinese population. Methods: Cross-sectional data of 284 patients with PTC were collected from the First Affiliated Hospital of Shandong First Medical University. The general clinical characteristics, serum selenium levels, and tumor pathological features were described in PTC. The association between serum selenium levels and pathological features in PTC was analyzed using SPSS 26.0 statistical software. Results: Our results showed that the median serum selenium level was 79.15 µg/L (IQR: 71.00 - 86.98 µg/L) in PTC patients. Serum selenium levels were lower in females than males (p = 0.035). Serum selenium levels were negatively correlated with the number of lymph node metastases (p = 0.048). High serum selenium (OR = 0.397, 95%CI: 0.217 - 0.725) and diastolic blood pressure (OR = 1.028, 95%CI: 1.005 - 1.051) were related factors for the incidence of bilateral tumors. High serum selenium (OR = 0.320, 95%CI: 0.166 - 0.617) and diastolic blood pressure (OR = 1.066, 95%CI: 1.031 - 1.103) were related factors for tumor multifocal incidence. Conclusions: The serum selenium levels of PTC patients in females were lower than males. High serum selenium levels might be a protective factor in PTC patients. Further research is necessary to better understand the influence of selenium on PTC progression.
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Carcinoma Papilar , Selenio , Neoplasias de la Tiroides , Masculino , Femenino , Humanos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Estudios Transversales , Carcinoma Papilar/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: A pseudoaneurysm of the superficial temporal artery is an uncommon clinical entity that has largely been linked with direct traumatic causes. Neurofibromatosis type 1 (NF1)-related vasculopathy is a rare cause of idiopathic arterial bleeding in the craniofacial region. OBSERVATIONS: A 46-year-old male with clinical features of NF1 presented to the hospital with an enlarging and tender right temporal mass without a history of trauma. Computed tomography angiography suggested the development of a pseudoaneurysm, and surgery was performed to resect the mass. Histopathological examinations showed focal interruption of the epithelium layer and elastic lamina, well-demarcated thickening of the smooth muscle layers of the arterial wall, supporting the diagnosis of pseudoaneurysm. LESSONS: NF1-associated vasculopathy is likely the predisposing factor for the development of a superficial temporal artery pseudoaneurysm.
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Arbutin, a widely used skin lightening agent, has raised concerns regarding its potential side effects. In this study, we investigated the impact of arbutin on Leydig cell function using an in vitro model. We measured medium androgen levels, as well as the gene and protein expression related to Leydig cell steroidogenesis. Rat immature Leydig cells from age of 35 days were exposed to arbutin at concentrations ranging from 0.5 to 50 µM for a duration of 3 hrs. Following treatment, we observed a significant inhibition of androgen secretion by Leydig cells at both the 5 and 50 µM concentrations of arbutin. Furthermore, at a concentration of 50 µM, arbutin effectively blocked the stimulatory effects of luteinizing hormone (LH) and 8Br-cAMP on androgen secretion. Subsequent analysis revealed that arbutin downregulated the expression of crucial genes involved in androgen production, including Lhcgr, Hsd3b1, Cyp17a1, and Srd5a1. In silico computer program analysis predicted that arbutin exhibits good absorption, possesses a long elimination half-life, and may have other potential toxicity such as hepatoxicity. Taken together, our results demonstrate that arbutin negatively influences Leydig cell function and androgen production, potentially impacting male reproductive health.
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Andrógenos , Células Intersticiales del Testículo , Ratas , Masculino , Animales , Andrógenos/toxicidad , Arbutina/metabolismo , Arbutina/farmacología , Ratas Sprague-Dawley , Hormona Luteinizante , Testosterona/metabolismoRESUMEN
Immune checkpoint inhibitors targeting PD-L1 lead to challenging patterns of efficacy and toxicity. Herein, by focusing on tracing the molecular biomarker of response to efficacy, we formulated a central hypothesis for the construction of theranostic functional monoclonal antibody incorporation with tracing ability based on fluorescence turn-on and controllable release strategies. Functional atezolizumab was constructed by in situ assembly of both biorthogonal group and controllable release group. The theranostic monoclonal antibodies achieved quantitative monitoring of PD-L1 on cells with different expression levels through biorthogonal light-up fluorescence, followed by the release of atezolizumab in combination with high tumor reduction conditions to promote immune activation. The combination of bio-orthogonal reaction-driven fluorescence turn-on and tumor microenvironment-responsive controllable release afforded theranostic bifunctional monoclonal antibodies for the detection of PD-L1 and combination therapy. Remarkably, these novel theranostics might be used as probes for fluorescent imaging and simultaneously achieving potent antitumor efficacy.
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Antígeno B7-H1 , Neoplasias , Humanos , Anticuerpos Monoclonales/farmacología , Microambiente TumoralRESUMEN
It has been discovered that some circular RNAs can serve as excellent therapeutic targets for breast cancer (BC). However, the biological role that circ ATAD3B plays in BC is not yet completely understood. As a result, the purpose of this work was to evaluate the function of circ_ATAD3B in the development of BC. Three different GEO datasets were used to compile the expression profiles of circRNAs related to BC (GSE101124, GSE165884, and GSE182471). CCK-8 and the production of clones, in addition to RT-PCR and western blot assays, were utilized in this study to evaluate the regulation of these three biological molecules in the process of BC carcinogenesis.circ_ATAD3B was the only potential BC-related circRNA that was significantly reduced in BC tumor tissues, and it functioned as a miR-570-3p sponge to suppress cell survival and proliferation, as stated by the aforementioned two algorithms. The expression of MX2 was boosted when circ_ATAD3B was used to sponge miR-570-3p. The inhibitory effect that circ_ATAD3B has on the malignant phenotype of BC cells was overcome by the expression of miR-570-3p through up-regulation and MX2 through down-regulation. The tumor suppressor circ_ATAD3B prevents cancer progression by regulating the miR-570-3p/MX2 pathway. Circ_ATAD3B may be a candidate for targeted therapy of breast cancer.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/genética , Proliferación Celular/genética , Algoritmos , Fenotipo , MicroARNs/genética , ATPasas Asociadas con Actividades Celulares Diversas/genética , Proteínas de la Membrana , Proteínas Mitocondriales , Proteínas de Resistencia a MixovirusRESUMEN
Facing the sudden outbreak of coronavirus disease 2019 (COVID-19), it is extremely urgent to develop effective antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Drug repurposing is a promising strategy for the treatment of COVID-19. To identify the precise target protein of marketed medicines, we initiate a chemical biological program to identify precise target of potential antivirus drugs. In this study, two types of recombinant human coronavirus SARS-CoV-2 RdRp protein capturing probes with various photoaffinity labeling units were designed and synthesized based on the structure of FDA-approved drugs stavudine, remdesivir, acyclovir, and aladenosine. Fortunately, it was found that one novel photoaffinity probe, RD-1, could diaplayed good affinity with SARS-CoV-2 RdRp around the residue ARG_553. In addition, RD-1 probe also exhibited potent inhibitory activity against 3CLpro protease. Taken together, our findings will elucidate the structural basis for the efficacy of marketed drugs, and explore a rapid and efficient strategy of drug repurposing based on the identification of new targets. Moreover, these results could also provide a scientific basis for the clinical application of marketed drugs.
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COVID-19 , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , ARN Polimerasa Dependiente del ARN/farmacología , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: Although nonfat milk has been used worldwide in the industrial dairy process, little is known about the effects of fat separation during the manufacturing process on skim milk's structural and digestive properties. This study investigated the effects of the manufacturing process on the structure and in vitro digestion properties of skim goat milk, particularly emphasizing fat separation. RESULTS: Changes in the surface charge and hydrophobicity of milk proteins caused by fat separation resulted in oxidation and aggregation in the subsequent homogenization, heat and spray-drying processing, which affected its digestibility. Compared with separation by dish separator (DS), skim milk after tubular centrifugal separation (CS) showed a higher initial and final digestibility. The CS samples also had a lower surface hydrophobicity level and higher free sulfhydryl content, ζ-potential, and average particle size (P < 0.05). Goat milk protein after CS was more readily oxidized and aggregated during the subsequent homogenization and heat treatment, as evidenced by the higher carbonyl content and particle size. Centrifugal separation also converted more ß-sheets to α-helices, thus promoting the aggregation of oxidized skim milk protein. CONCLUSION: The skim milk after CS and DS demonstrated different structural and digestive properties. Skim goat milk products after CS were more susceptible to oxidant-induced protein structural changes, resulting in higher protein digestibility. These findings provide insights into the mechanism involved in the control of gastric digestion of skim milk during manufacturing process. © 2023 Society of Chemical Industry.
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Cabras , Proteínas de la Leche , Animales , Proteínas de la Leche/análisis , Leche/química , Oxidación-Reducción , DigestiónRESUMEN
Background: Shashi-Pena syndrome (SHAPNS) is a developmental disorder caused by mutations in additional sex combs-like Protein 2 (ASXL2). Since 2016, only 12 cases from 10 families have been reported. However, neonatal period characteristics remain largely unknown. Herein, we report a case with a pathogenic variant in ASXL2 in a newborn. Case Description: A newborn was diagnosed with a previously unreported de novo truncating mutation in ASXL2 (NM_018263.6) at 21 days and the clinical characteristics of all probands with ASXL2-related SHAPNS was reported in the literature. He had persistent hypoglycemia caused by inappropriate insulin levels and achieved stable glucose levels after octreotide treatment. Magnetic resonance imaging (MRI) revealed a small cerebellum, and fundoscopy showed bilateral retinal paving-stone-like white lesions. The results of trio-based whole exome sequencing (WES) were returned on the 21st day of life, and a heterozygous de novo truncating pathogenic c.1792C>T (p.Gln598*) variant in exon 11 of the ASXL2 gene was identified. The clinical features of our patient and another 10 probands with ASXL2-related SHAPNS reported in the literature were included in this review. More than half shared recognizable clinical features, including hypertelorism (11/11), broad nasal tip (10/11), arched eyebrows (9/11), a large V-shaped glabellar nevus flammeus on the forehead (9/11), low-set ears (8/11), posteriorly rotated ears (7/11), proptosis (6/11) and deep palm creases (6/11). Major clinical issues included feeding difficulties (10/11), developmental delay (10/11), skeletal and/or extremity abnormalities (8/11), progressive macrocephaly (8/11), hypotonia (8/11), hypoglycemia (6/11) and seizures (6/11). Neurodevelopmental regression was possible in patients (2/11) with normal MRI findings who later developed nonfebrile seizures. Conclusions: We present a newborn diagnosing the SHAPNS by trio-WES, which is the earliest age of diagnosis. The application of octreotide for hypoglycemia, the small cerebellum and bilateral paving-stone-like white lesions of the retinas are described for the first time in an individual with ASXL2-related SHAPNS. Additional clinical reports of neonates with damaging ASXL2 variants are necessary to verify the mechanism and optimal treatment of ASXL2-related hypoglycemia, neurological damage and optic impairment. Neurological, endocrinological, ophthalmological, and rehabilitative follow-ups of these patients are necessary and important.
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Ovomucin (OVM) is a natural glycoprotein with various biological activities but poor solubility. This study aimed to enhance the solubility of OVM by using an ultrasonic-assisted method. The effect of ultrasound (US) on the structure, thermal stability and biological functions of OVM aggregates was evaluated. It was found that insoluble OVM aggregates were dissociated and the solubility increased significantly to 90.0 % after US under 400 W for 45 min. US also improved the onset temperature (To) and denaturation temperature (Td) of OVM. More importantly, the cholesterol binding capacity of both OVM and its digestion products were significantly improved after US (p < 0.05). The gastrointestinal digestion products of US-OVM also showed higher α-amylase and α-glucosidase inhibition than native OVM aggregates. US-induced dissociation of OVM aggregates and the conversion of ß-sheet and ß-turn to random coil, resulting in the exposure of hydrophobic binding sites may be an important reason for the enhanced stability and adsorption capacity. These findings suggested that US was an effective method for preparing soluble OVM and improved its adsorption capacity, which can further facilitate the application of OVM in the food industry.
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Inmunoglobulina E , Ovomucina , Ovomucina/química , Temperatura , Interacciones Hidrofóbicas e Hidrofílicas , Inmunoglobulina GRESUMEN
Glycoproteins formed by covalent links between oligosaccharide and polypeptides are abundant in various food sources. They are less sensitivity to gastrointestinal enzymes, and hence many of them undergo fermentation in the colon by microorganisms. Therefore, the confer various health benefits on the intestinal ecosystem. However, the current understanding of the effect of glycoproteins on intestinal microorganisms and gut health is limited. This is probably due to their heterogeneous structures and complex metabolic programming patterns. The structure and biological activities of glycoproteins and their microbial metabolites were summarized in this review. The metabolic pathways activated by intestinal bacteria were then discussed in relation to their potential benefits on gut health. Food-derived glycoproteins and their metabolites improve gut health by regulating the intestinal bacteria and improving intestinal barrier function, thereby amplifying immune response. The data reviewed here show that food-derived glycoproteins are promising candidates for preventing various gastrointestinal diseases. Further studies should explore the interaction mechanisms between intestinal microorganisms and host metabolites.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1987857 .
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Ecosistema , Enfermedades Gastrointestinales , Humanos , Alimentos , GlicoproteínasRESUMEN
As the most common subtype of lung cancer, non-small cell lung cancer (NSCLC)is responsible for a large proportion of global cancer-caused deaths. The implication of long non-coding RNAs (lncRNAs) as tumor-suppressor or carcinogenic genes in NSCLC has been widely documented. Our study sought to investigate the performance of lncRNA RAMP2 antisense RNA1 (RAMP2-AS1) in NSCLC. GEPIA bioinformatics tool and RT-qPCR were applied for assessing the expression of RAMP2-AS1 and its neighboring gene receptor activity-modifying protein 2 (RAMP2) in NSCLC. Functional assays including CCK-8 assay, colony formation assay as well as caspase-3 activity analysis and Transwell invasion assays were applied for detecting the biological phenotypes of NSCLC cells. Interaction among RAMP2-AS1, RAMP2 and T-cell intracellular antigen 1cytotoxic granule associated RNA binding protein (TIA1) was evaluated by RNA immunoprecipitation and pulldown assays. We found that RAMP2-AS1 and RAMP2 were downregulated in NSCLC. Overexpression of RAMP2-AS1 hampered proliferation and invasion, whereas induced apoptosis of NSCLC cells. Mechanistically, RAMP2-AS1 interacted with TIA1 to stabilize the mRNA of RAMP2. In conclusion, we first uncovered that RAMP2-AS1 stabilized RAPM2 mRNA through TIA1 to inhibit the progression of NSCLC, providing new insight to improve the treatment efficacy of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , ARN Mensajero/genética , Proteína 2 Modificadora de la Actividad de Receptores/genética , Proteína 2 Modificadora de la Actividad de Receptores/metabolismo , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Movimiento Celular/genética , Antígeno Intracelular 1 de las Células T/genética , Antígeno Intracelular 1 de las Células T/metabolismoRESUMEN
BACKGROUND: Severe neonatal thrombocytopenia is a rare disease with multiple etiologies. Severe thrombocytopenia with bleeding is life-threatening and has attracted significant attention from clinicians. However, only a few studies have focused on the association between severe thrombocytopenia and bleeding. Thus, this study aimed to describe the neonates' postnatal age at which severe thrombocytopenia was first recognized, clinical characteristics, bleeding patterns, and outcomes and to evaluate the association between minimum platelet count and bleeding. METHODS: A single-center retrospective cohort study for neonates with severe thrombocytopenia (platelet count ≤ 50 × 109/L) was conducted. Neonates who were admitted to our neonatal intensive care unit between October 2016 and February 2021 and developed severe thrombocytopenia were analyzed. Data were collected retrospectively until the patients were referred to other hospitals, discharged, or deceased. RESULTS: Among the 5819 neonatal inpatients, 170 with severe thrombocytopenia were included in this study. More than 30% of the patients had severe thrombocytopenia in the first 3 days of life. Among the 118 neonates with bleeding, 47 had more than one type of pathological bleeding. Neonates with very severe thrombocytopenia (point estimate: 53.7%, 95% confidence interval [CI]: 44.2%-63.1%) had a higher incidence rate of cutaneous bleeding than those with severe thrombocytopenia (point estimate: 23.4%, 95% CI: 12.3%-34.4%). The gestational age (median: 36.2 [interquartile range [IQR]: 31.4-39.0] weeks) and birth weight (median: 2310 [IQR: 1213-3210] g) of the major bleeding group were the lowest among no bleeding, minor bleeding, and major bleeding groups. Regression analysis controlled for confounders and confirmed that a lower platelet count (odds ratio [OR]: 2.504 [95% CI: 1.180-5.314], P = 0.017) was associated with a significant increase in the rate of bleeding. Very severe thrombocytopenia (point estimate: 49.1%, 95% CI: 39.6%-58.6%) had a higher rate of platelet transfusion than severe thrombocytopenia (point estimate: 5.7%, 95% CI: 0.7%-10.7%). The mortality rate was higher in neonates with bleeding than in those without bleeding (point estimates with 95% CI: 33.1% [24.4%-41.7%] vs. 7.7% [0.2%-15.2%]). CONCLUSIONS: These findings describe the incidence of severe thrombocytopenia and demonstrate that a lower platelet count is associated with an increased bleeding rate in patients with severe thrombocytopenia.
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Trombocitopenia , Recién Nacido , Humanos , Lactante , Estudios Retrospectivos , Trombocitopenia/complicaciones , Hemorragia/etiología , Recuento de Plaquetas , Transfusión de Plaquetas/efectos adversosRESUMEN
Background: Sodium-glucose co-transporters-2 (SGLT-2) has been reported as overexpressed in tumors including pancreatic cancer (PC). The aim of this study was to investigate the clinicopathological and prognostic significance, as well as the potential role of SGLT-2 in PC development and progression. Methods: The expression of SGLT-2 was assessed using The Cancer Genome Atlas (TCGA) PC dataset (179 cases). The overall survival (OS) and disease-free survival (DFS) of PC patients with high and low SLC5A2 expression were compared using the online database Gene Expression Profiling Interactive Analysis (GEPIA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool. The genetic correlations of SLC5A2 genes in different subtypes of PC were analyzed by using cBioPortal and LinkedOmics online databases. Results: No relationship between SGLT-2 expression and PC risk factors, tumor location, histology grade, or tumor-node-metastasis (TNM) stage was identified. Further, SGLT-2 could not be used as prognosis predictor. The KEGG analyses demonstrated that high SGLT-2 expression is correlated with activation of pathways related with chemical carcinogenesis, energy metabolism and drug metabolism, and the suppression of nucleotide excision repair, messenger RNA (mRNA) surveillance, and cell cycle regulation. Specifically, high SGLT-2 level also coexisted with upregulation of gene symbols for pancreatic progenitor subtype for PC. Conclusions: There is potential for SGLT-2 as a potential target for PC treatment, and SGLT-2 inhibitors should be further evaluated as a novel therapy in PC.