A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

Comparison of Whey Proteome and Glycoproteome in Bovine Colostrum and Mature Milk.

Milk samples were collected from 10 cows, in the colostrum (3-4 days) and mature (90 days) lactation stage, to assess the differential expression of all whey proteins and N-glycoproteins. In total, 240 whey proteins and 315 N-glycosylation sites on 214 glycoproteins were quantified. GO annotations, KEGG pathway analysis, and protein classification were performed to understand the similarities and differences of the biological functions of whey proteins and N-glycoproteins among different lactation stages in bovine milk. Furthermore, differential expression of whey proteins and whey N-glycosylated proteins was found between different lactation stages. The related changes of biological functions in differentially expressed proteins were discussed. For example, the increased frequency of glycosylation on lactoferrin and folate receptor alpha occurring in bovine colostrum may provide protection and stimulate development of the newborn calf. Our study thereby improves understanding of variations of glycosylation sites on milk glycoproteins among lactation stages.

Dietary yeast glycoprotein supplementation improves the growth performance, intestinal health and disease resistance of largemouth bass (Micropterus salmoides) fed low-fishmeal diets.

The active ingredients extracted from yeast are important for regulating animal health. The aim of the current research was to explore the impacts of dietary yeast glycoprotein (YG) on the growth performance, intestinal morphology, antioxidant capacity, immunity and disease resistance of largemouth bass (Micropterus salmoides). A total of 375 juvenile fish (6.00 ± 0.03 g) were allocated into 15 fiberglass tanks. Triplicate tanks were assigned to each diet. The dietary YG inclusion was as follows: the first group was given a high fishmeal diet (40% fishmeal, 0% YG) (FM) and the second group was given a low fishmeal diet (30% fishmeal and 15% soybean meal, 0% YG) (LFM). The fish in the third, fourth and fifth groups were fed the LFM diet supplemented with 0.5% (LFM+YG0.5), 1.0% (LFM+YG1.0) and 2.0% (LFM+YG2.0) YG, respectively. After a 60- day feeding trial, a challenge test using A. hydrophila was carried out. The results showed that the final body weight (FBW) and weight gain rate (WGR) in the LFM+YG2.0 group were significantly higher than those in the LFM group and were no significantly different from those in the FM group. This may be partially related to the activation of the target of rapamycin (TOR) signaling pathway. Dietary YG supplementation enhanced intestinal physical barriers by upregulating the intestinal tight junction protein related genes (claudin1, occludin and zo2) and improving the structural integrity of the gut, which may be partially associated with AMPK signaling pathway. Moreover, dietary YG increased the antioxidant capacity in the gut, upregulated intestinal anti-inflammatory factors (il-10, il1-1ß and tgf-ß) and downregulated proinflammatory factors (il-1ß and il-8), which may be partially related to the Nrf2/Keap1 signaling pathways. The results of the challenge test indicated that dietary supplementation with 0.5 or 1.0% YG can increase the disease tolerance of largemouth bass against A. hydrophila. In conclusion, the present results indicated that dietary supplementation with YG promotes the growth performance, intestinal immunity, physical barriers and antioxidant capacity of largemouth bass. In addition, 1.0% of dietary YG is recommended for largemouth bass based on the present results.

A novel glycoprotein from earthworm extract PvE-3: Insights of their characteristics for promoting diabetic wound healing and attenuating methylglyoxal-induced cell damage.

Diabetic chronic wound is a worldwide medical burden related to overdosed methylglyoxal (MGO) synthesis, which is the major precursor of glycation of proteins and DNA and is related to the dysfunction of dermal cells thus leading to chronic refractory wounds. Previous studies proved that earthworm extract accelerates diabetic wound healing and possesses cell proliferation and antioxidative effects. However, the effects of earthworm extract on MGO-damaged fibroblasts, the inner mechanisms of MGO-induced cell damage and the functional components in earthworm extract are still poorly understood. Firstly, we evaluated the bioactivities of the earthworm extract PvE-3 on the diabetic wound model and the diabetic related cell damage model. Then the mechanisms were investigated through transcriptomics, flow cytometry and fluorescence probe. The results revealed that PvE-3 promoted diabetic wound healing and protected fibroblast function in cell-damaged conditions. Meanwhile, the high-throughput screening implied the inner mechanisms of diabetic wound healing and PvE-3 cytoprotection effect were involved in the muscle cell function, the cell cycle regulation and the mitochondrial transmembrane potential depolarization. The functional glycoprotein isolated from PvE-3 possessed EGF-like domain which had a strong binding affinity with EGFR. The findings provided references to explore the potential treatments of diabetic wound healing.

Characterization and comparison site-specific N-glycosylation profiling of milk fat globule membrane proteome in donkey and human colostrum and mature milk.

Milk fat globule membrane (MFGM) proteins are highly glycosylated and involved in various biological processes within the body. However, information on site-specific N-glycosylation of MFGM glycoproteins in donkey and human milk remains limited. This study aimed to map the most comprehensive site-specific N-glycosylation fingerprinting of donkey and human MFGM glycoproteins using a site-specific glycoproteomics strategy. We identified 1,360, 457, 2,617, and 986 site-specific N-glycans from 296, 77, 214, and 196 N-glycoproteins in donkey colostrum (DC), donkey mature milk (DM), human colostrum (HC), and human mature milk (HM), respectively. Bioinformatics was used to describe the structure-activity relationships of DC, DM, HC, and HM MFGM N-glycoproteins. The results revealed differences in the molecular composition of donkey and human MFGM N-glycoproteins and the dynamic changes to site-specific N-glycosylation of donkey and human MFGM glycoproteins during lactation, deepening our understanding of the composition of donkey and human MFGM N-glycoproteins and their potential physiological roles.

Lycium barbarum polysaccharide-glycoprotein ameliorates ionizing radiation-induced epithelial injury by regulating oxidative stress and ferroptosis via the Nrf2 pathway.

Radiation-induced oral mucositis (RIOM) is considered to be the most common acute side effect of radiation therapy and occurs during intentional or accidental radiation exposure. Antioxidant synthesis agents have been reported to protect against or alleviate the development of mucositis, but the resulting side effects of chemical synthesis agents limit their use in clinical practice. Lycium barbarum polysaccharide-glycoprotein (LBP), a polysaccharide extract of the Lycium barbarum fruit, has superior antioxidant capacity and biosafety and is a potential option for radiation prevention and treatment. Here, we aimed to investigate whether LBP conferred radioprotection against ionizing radiation-induced oral mucosal damage. We found that LBP exerted radioprotective effects in irradiated HaCaT cells, improving cell viability, stabilizing mitochondrial membrane potential, and decreasing cell death. LBP pretreatment reduced oxidative stress and ferroptosis in radioactivity-damaged cells by activating the transcription factor Nrf2 and promoting its downstream targets, such as HO-1, NQO1, SLC7A11, and FTH1. Knockdown of Nrf2 eliminated the protective effects of LBP, implying the essential role of Nrf2 in LBP activity. Additionally, the topical application of LBP thermosensitive hydrogel on rat mucosa resulted in a significant decrease in ulcer size in the irradiated group, suggesting that LBP oral mucoadhesive gel may be a potential tool for the treatment of irradiation. In conclusion, we demonstrated that LBP attenuates ionizing radiation-induced oral mucosa injury by reducing oxidative stress and inhibiting ferroptosis via the Nrf2 signaling pathway. LBP may be a promising medical countermeasure against RIOM.

Release of bifidogenic N-glycans from native bovine colostrum proteins by an endo-ß-N-acetylglucosaminidase.

Milk glycoproteins play various biological roles including antibacterial, antiviral activities, modulating immune responses in living organisms. Released N-glycans from milk glycoproteins act as growth substrates for infant-associated bifidobacteria, which are key members of the breastfed infant's gut. To date, the mechanisms, and contributions of glycans to the biological activities of glycoproteins remain to be elucidated. Only by testing both the released glycans and the deglycosylated protein in their native (i.e., non-denatured) form, can the individual contribution to the biological activity of glycoproteins be elucidated. However, for conventional enzymatic and chemical deglycosylation strategies to work efficiently, glycoprotein denaturation is required, which alters the protein native shape, hindering further investigations of its biological roles. An endo-ß-N-acetylglucosaminidase (EndoBI-1) from Bifidobacterium longum subsp. infantis ATCC 15697 (B. infantis) was characterized as having the ability to release N-glycans from bovine milk glycoproteins efficiently, without the denaturation. In this study, the activity of EndoBI-1 was compared to a commercial enzyme to release N-glycans, the peptide-N-glycosidase F (PNGase F), using dairy glycoproteins as the substrate. The kinetic evaluation showed that EndoBI-1 displayed higher activity on native glycoproteins than PNGase F, with 0.036 mg/mL×min and 0.012 mg/mL×min glycan release, respectively. EndoBI-1 released a broader array of glycan structures compared to PNGase F from native glycoproteins. Thirty-two and fifteen distinct compositions were released from the native glycoproteins by EndoBI-1 and PNGase F, respectively, as characterized by advanced mass spectrometry. EndoBI-1 can be considered a promising enzyme for the release of N-glycans and their protein backbone in the native form, which will enable effective glycan release and will facilitate subsequent investigations to reveal their contribution to glycoproteins' biological roles.

Enteromorpha polysaccharide and yeast glycoprotein mixture improves growth, antioxidant activity, serum lipid profile and regulates lipid metabolism in broiler chickens.

This study aimed to analyze the growth performance, antioxidant activity, serum lipid profile, meat quality, and lipid metabolism of broiler chickens fed mixtures containing Enteromorpha polysaccharide (EP) and yeast glycoprotein (YG). A total of 400 one-day-old broiler chickens were randomly divided into 4 treatment groups of 10 replicates with 10 birds each replicate. The dietary treatments consisted of the control group (fed basal diet), and diets supplemented with Enteromorpha polysaccharide (EP; 400 mg/kg), yeast glycoprotein (YG;400 mg/kg), and EP+YG (200 mg/kg EP + 200 mg/kg YG). Compared with the control group, EP+YG supplementation enhanced growth performance and significantly reduced (P < 0.05) serum total triglyceride (TG), cholesterol (CHOL), and low-density lipoprotein LDL levels, and increased high-density lipoprotein (HDL) levels. Besides, birds fed EP+YG supplemented diet exhibited higher (P < 0.05) serum catalase (CAT), total antioxidant capacity, superoxide dismutase (SOD), and lower malonaldehyde (MDA) activities, and upregulated expressions of related genes, such as nuclear factor-erythroid factor 2-related factor 2 (NRF2), SOD1, and glutathione peroxidase 4 (GPX4) in the liver and intestinal tissues than the control group. Interestingly, higher (P < 0.05) serum SOD and lower MDA contents were observed in the EP+YG group than in either EP or YG group, suggesting a synergetic effect. Breast meat from EP+YG supplemented group had significantly higher redness value (a*), and lower pH24, total saturated fatty acid profiles, C14:0, C16:0, C18:0 fatty acid, atherogenic index, and thrombogenicity index than meat from the control group (P < 0.05). Furthermore, the mRNA expressions of fatty acid synthesis genes were downregulated (P < 0.05), whereas lipid ß-oxidation-related genes were upregulated (P < 0.05) in the liver of the EP+YG supplemented group than in the control group. Overall, our data suggest that dietary EP+YG inclusion may have a synergistic effect, and therefore improve growth performance, regulate serum biochemical indexes, enhance antioxidant activity, and modulate lipid metabolism in broilers, indicating that it is a potential feed additive for chickens.

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma.

BACKGROUND: Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing. AIM: To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma (ESCC) via two complementary approaches. METHODS: Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins, we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis (2-DE)-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel, followed by validation of candidate glycoprotein biomarkers by Western blot. RESULTS: 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins, respectively, with 15 in common, demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches. Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC. Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D, and the down-regulation of total haptoglobin, high-mannose clusterin, and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues. The serum levels of glycosylated fractions of clusterin, proline-arginine-rich end leucine-rich repeat protein, and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls. CONCLUSION: Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC, which will be a valuable resource for future investigations.

How Epstein-Barr virus envelope glycoprotein gp350 tricks the CR2? A molecular dynamics study.

The connection of Epstein Barr virus (EBV) with diseases such as Burkitt Lymphoma, Hodgkin disease, multiple sclerosis, systemic lupus erythematosus and various B-cell lymphomas made EBV glycoproteins one of the most popular vaccine immunogens. As a protein being encoded by EBV, the viral membrane envelope protein gp350 is studied extensively due to its abundancy on the surface and its interaction with complementary receptor, CR2. The binding of CR2 and gp350 not only leads to the entrance of the virus to the B-cells, but also prevents CR2 and C3d protein interactions that are required for immune response. Thus, understanding the inhibition of gp350 activity is crucial for vaccine development. Although, the active residues on gp350 structure were determined by several mutational studies, the exact mechanism of CR2 binding is still not clear. To this end, we have performed molecular docking followed by molecular dynamics simulations and MM-PBSA on wildtype and several mutated gp350 and CR2 structures. Apart from identifying crucial amino acids, the results of per-residue decomposition energy analysis clarified the individual energy contributions of amino acids and were also found to be accurate in differentiating the active site residues in CR2 binding. Here, we highlight the role of binding region residues (linker-1) but more interestingly, the dynamic relation between the distant sites of gp350 (linker-2 and D3 residues) and CR2. These findings can lead further vaccine development strategies by pointing to the importance of computationally found novel regions that can be potentially used to modulate gp350 activity.

Upregulation of protein N-glycosylation plays crucial roles in the response of Camellia sinensis leaves to fluoride.

The tea plant (Camellia sinensis) is one of the three major beverage crops in the world with its leaves consumption as tea. However, it can hyperaccumulate fluoride with about 98% fluoride deposition in the leaves. Our previously studies found that cell wall proteins (CWPs) might play a central role in fluoride accumulation/detoxification in C. sinensis. CWP is known to be glycosylated, however the response of CWP N-glycosylation to fluoride remains unknown in C. sinensis. In this study, a comparative N-glycoproteomic analysis was performed through HILIC enrichment coupled with UPLC-MS/MS based on TMT-labeling approach in C. sinensis leaves. Totally, 237 N-glycoproteins containing 326 unique N-glycosites were identified. 73.4%, 18.6%, 6.3% and 1.7% of these proteins possess 1, 2, 3, and ≥4 modification site, respectively. 93.2% of these proteins were predicted to be localized in the secretory pathway and 78.9% of them were targeted to the cell wall and the plasma membrane. 133 differentially accumulated N-glycosites (DNGSs) on 100 N-glycoproteins (DNGPs) were detected and 85.0% of them exhibited upregulated expression after fluoride treatment. 78.0% DNGPs were extracellular DNGPs, which belonged to CWPs, and 53.0% of them were grouped into protein acting on cell wall polysaccharides, proteases and oxido-reductases, whereas the majority of the remaining DNGPs were mainly related to N-glycoprotein biosynthesis, trafficking and quality control. Our study shed new light on the N-glycoproteome study, and revealed that increased N-glycosylation abundance of CWPs might contribute to fluoride accumulation/detoxification in C. sinensis leave.

Prevention of SARS-CoV-2 cell entry: insight from in silico interaction of drug-like alkaloids with spike glycoprotein, human ACE2, and TMPRSS2.

COVID-19 is a respiratory disease caused by SARS-CoV-2, an enveloped positive sense RNA virus. The SARS-CoV-2 spike glycoprotein, human angiotensin-converting enzyme 2 (ACE2) and human transmembrane protease serine 2 (TMPRSS2) are essential for the host cell-mediated viral entry. Targeting these proteins represent viable options to stop the first stage of infection and transmission. Hence, 97 alkaloids from African medicinal plants with reported antiviral activity were evaluated for this purpose via in silico studies. These alkaloids were docked for their interactions with SARS-CoV-2 spike glycoprotein, ACE2, and TMPRSS2. Top 20 alkaloids with highest binding affinities were further screened for their interactions with spike glycoprotein of SARS-CoV and MERS-CoV, and with ACE2-SARS-CoV-2 receptor-binding domain complex (ACE2-RBD). The energy profiling, molecular dynamics simulation (MDS), binding free energy base on Molecular Mechanics/Generalized Born Surface Area (MMGBSA), clustering of MDS trajectories, and virtual physicochemical and pharmacokinetic screening of the best docked alkaloids were performed. Results revealed that more than 15 alkaloids interacted better than the reference compounds. 10-Hydroxyusambarensine and Cryptospirolepine were docked in a similar binding pattern to the S1-specificy pocket of TMPRSS2 as camostat (reference inhibitor). The strong binding affinities, stability of the alkaloid-protein complexes and amino acid interactions displayed by cryptospirolepine, 10-hydroxyusambarensine, and cryptoquindoline with important binding hotspots of the proteins suggest these alkaloids have the potential of altering the capacity of SARS-CoV-2 membrane mediated host cell entry. Further in vitro and in vivo evaluation of these "drug-like" alkaloids as potential inhibitors of coronavirus cell entry is proposed.Communicated by Ramaswamy H. Sarma.

Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis.

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.

Screening of potential spike glycoprotein / ACE2 dual antagonists against COVID-19 in silico molecular docking.

The novel coronavirus disease has spread rapidly and caused sustained pressure on economic and medical resources to many countries. Vaccines and effective drugs are needed to fight against the epidemic. Traditional Chinese Medicine (TCM) plays an important and effective role in the treatment of COVID-19. Therefore, the active components of TCM are potential structural basis for the discovery of antiviral drugs. Through screening by molecular docking, Oleanolic acid, Tryptanthrin, Chrysophanol and Rhein were found to have better spike protein and ACE2 inhibitory activity, which could block the invasion and recognition of SARS-CoV-2 at the same time, should be investigated as antiviral candidates.

Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy.

(1) Background: Melanoma is an aggressive neoplasm derived from melanocyte precursors with a high metastatic potential. Responses to chemotherapy and immunotherapy for melanoma remain weak, underlining the urgent need to develop new therapeutic strategies for the treatment of melanoma. (2) Methods: The viability of NHDF and A375 cell cultures after the administration of the tested isoxazole derivatives was assessed after 24-h and 48-h incubation periods with the test compounds in the MTT test. ROS and NO scavenging analyses, a glycoprotein-P activity analysis, a migration assay, a test of apoptosis, and a multiple-criteria decision analysis were also performed. (3) Results: All compounds that were tested resulted in a slower migration of melanoma neoplastic cells. The mechanism of the antitumor activity of the tested compounds was confirmed-i.e., the pro-apoptotic activity of the compounds in A375 cell cultures. Compound O7K qualified for further research. (4) Conclusions: All the tested compounds inhibited the formation of melanoma metastases and demonstrated the ability to reduce the risk of developing drug resistance in the tumor. The MCDA results showed that O7K showed the strongest antitumor activity.

Improved assay system for acidic peptide: N-glycanase (aPNGase) activity in plant extracts.

Plant acidic peptide: N-glycanase (aPNGase) release N-glycans from glycopeptides during the degradation process of glycoproteins in developing or growing plants. We have previously developed a new method to detect the aPNGase activity in crude extracts, which is prerequisite for the construction of aPNGase knockout or overexpression lines. However, this method has the disadvantage of requiring de-sialylation treatment and a lectin chromatography. In this study, therefore, we improved the simple and accurate method for detecting aPNGase activity using anion-exchange HPLC requiring neither the desialylation treatment nor the lectin affinity chromatography.

Identification and functional analysis of a pollen fertility-associated gene GhGLP4 of Gossypium hirsutum L.

KEY MESSAGE: Cotton male fertility-associated gene GhGLP4, encoding a germin-like protein, is essential for anthers development by keeping ROS homeostasis through reducing H2O2 level. Utilization of heterosis is an important way to increase cotton yield and improve fiber quality in hybrid cotton development programs. Male sterility is used in the development of cotton hybrids to reduce the cost of hybrid seed production by eliminating the process of emasculation. From the transcriptome analysis of genic male sterile mutant (ms1) and its background C312 of G. hirsutum, a gene encoding germin-like protein (GhGLP4) was found significantly down-regulated in different developmental stages of ms1 anthers. To explore the gene function in cotton fertility, GhGLP4 was further studied and interfered by virus-induced gene silencing. In the GhGLP4 interfered cotton lines, the expression level of GhGLP4 was significantly decreased in the stamens, and the down-regulation of GhGLP4 resulted in pollen sac closure, stigma exertion, filament shortening, decrease in the number of anthers and complete male sterility. The expression levels of respiratory burst oxidase homologs (Rboh, NADPH oxidase) were significantly altered. Further investigation showed that the SOD activity decreased while the H2O2 content increased in the atypical stamens. These results indicated that GhGLP4 gene affected the cotton anther development through maintenance of ROS homeostasis by H2O2 reduction.

The Prognostic Value of Leucine-Rich α2 Glycoprotein 1 in Pediatric Spinal Cord Injury.

OBJECTIVE: Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). METHODS: This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. RESULTS: All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 µg/ml. CONCLUSIONS: Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI.

Breast Milk: A Source of Functional Compounds with Potential Application in Nutrition and Therapy.

Breast milk is an unbeatable food that covers all the nutritional requirements of an infant in its different stages of growth up to six months after birth. In addition, breastfeeding benefits both maternal and child health. Increasing knowledge has been acquired regarding the composition of breast milk. Epidemiological studies and epigenetics allow us to understand the possible lifelong effects of breastfeeding. In this review we have compiled some of the components with clear functional activity that are present in human milk and the processes through which they promote infant development and maturation as well as modulate immunity. Milk fat globule membrane, proteins, oligosaccharides, growth factors, milk exosomes, or microorganisms are functional components to use in infant formulas, any other food products, nutritional supplements, nutraceuticals, or even for the development of new clinical therapies. The clinical evaluation of these compounds and their commercial exploitation are limited by the difficulty of isolating and producing them on an adequate scale. In this work we focus on the compounds produced using milk components from other species such as bovine, transgenic cattle capable of expressing components of human breast milk or microbial culture engineering.

Assessing the In Vitro Inhibitory Effects on Key Enzymes Linked to Type-2 Diabetes and Obesity and Protein Glycation by Phenolic Compounds of Lauraceae Plant Species Endemic to the Laurisilva Forest.

Methanolic leaf extracts of four Lauraceae species endemic to Laurisilva forest (Apollonias barbujana, Laurus novocanariensis, Ocotea foetens and Persea indica) were investigated for the first time for their potential to inhibit key enzymes linked to type-2 diabetes (α-amylase, α-glucosidase, aldose reductase) and obesity (pancreatic lipase), and protein glycation. Lauraceae extracts revealed significant inhibitory activities in all assays, altough with different ability between species. In general, P. indica showed the most promissing results. In the protein glycation assay, all analysed extracts displayed a stronger effect than a reference compound: aminoguanidine (AMG). The in vitro anti-diabetic, anti-obesity and anti-glycation activities of analysed extracts showed correlation with their flavonols and flavan-3-ols (in particular, proanthocyanins) contents. These Lauraceae species have the capacity to assist in adjuvant therapy of type-2 diabetes and associated complications, through modulation of the activity of key metabolic enzymes and prevention of advanced glycation end-products (AGEs) formation.