Exploring the partial degradation of polysaccharides: Structure, mechanism, bioactivities, and perspectives.

Polysaccharides are promising biomolecules with lowtoxicity and diverse bioactivities in food processing and clinical drug development. However, an essential prerequisite for their applications is the fine structure characterization. Due to the complexity of polysaccharide structure, partial degradation is a powerful tool for fine structure analysis, which can effectively provide valid information on the structure of backbone and branching glycosidic fragments of complex polysaccharides. This review aims to conclude current methods of partial degradation employed for polysaccharide structural characterization, discuss the molecular mechanisms, and describe the molecular structure and solution properties of degraded polysaccharides. In addition, the effects of polysaccharide degradation on the conformational relationships between the molecular structure and bioactivities, such as antioxidant, antitumor, and immunomodulatory activities, are also discussed. Finally, we summarize the prospects and current challenges for the partial degradation of polysaccharides. This review will be of great value for the scientific elucidation of polysaccharide fine structures and potential applications.

Comprehensive analysis in the nutritional composition, phenolic species and in vitro antioxidant activities of different pea cultivars.

In this study, ten pea (Pisum sativum L.) varieties were compared in their nutrient composition, phenolic compounds, antioxidant properties and their diversity were deciphered by multivariate analysis of correlation analysis and principal component analysis (PCA). The ten pea cultivars are rich in nutrients with different contents in lipid (0.57 to 3.52%), dietary fiber (11.34 to 16.13%), soluble sugar (17.53 to 23.99%), protein (19.75 to 26.48%) and starch (32.56 to 48.57%). Through the UPLC-QTOF-MS and HPLC-QQQ-MS/MS analysis, the ethanol extracts of ten peas mainly included 12 kinds of phenolic substances and showed good antioxidant activities on the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). The phenolic content and protocatechuic acid showed a positive correlation with antioxidant capacity. All results provide theoretical basis for the development and rational application of different varieties of peas and their related products.

Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: Case reports.

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

Usefulness of controlled attenuation parameter and liver stiffness measurement for detecting increased arterial stiffness in asymptomatic populations in China.

In recent studies, vibration-controlled transient elastography (FibroScan) has been reported as an alternative noninvasive approach for measuring liver steatosis and fibrosis. The present study aimed to investigate the feasibility of FibroScan controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) in the detection of increased arterial stiffness in asymptomatic populations in China.A retrospective cohort recruiting 4747 asymptomatic patients with no underlying causes of liver disease and having FibroScan and brachial-ankle pulse wave velocity (baPWV) during wellness check-up was covered. Nonalcoholic fatty liver disease (NAFLD) was defined as a CAP ≥238 dB/m. NAFLD with significant fibrosis was defined as an LSM ≥7.3 kPa in the presence of NAFLD. Increased arterial stiffness was determined as a BaPWV ≥1.4m/second.Among the 4747 study participants, 1596 subjects (33.6%) suffered from increased arterial stiffness. The prevalence of increased arterial stiffness progressively increased across CAP quartiles and LSM quartiles in NAFLD (23.5%, 30.8%, 38.3%, 43.7%, P < .001 and 33.1%, 36.8%, 40.4%, 48.2%, P < .001, respectively). After conventional cardiovascular risk factors were adjusted (age, sex, overweight, diabetes mellitus, hypertension, hypercholesterolemia, and current smoking habits), multivariate logistic regression analysis revealed that CAP (odd ratio [OR] = 1.005; 95% confidence interval [CI]: 1.003-1.006; P < .001), NAFLD (OR = 1.427; 95% CI: 1.212-1.681; P < .001), LSM in NAFLD (OR = 1.073; 95% CI: 1.023-1.125; P = .003), and significant fibrosis in NAFLD (OR = 1.480; 95% CI: 1.090-2.010; P = .012) were independently associated with increased arterial stiffness. Furthermore, in a multivariate logistic regression analysis, OR (95% CI) for the maximal vs. the minimal quartile of CAP was 1.602 (1.268-2.024), and that of LSM in NAFLD was 1.362 (1.034-1.792) after adjustment for the above-mentioned risk factors. Notably, NAFLD and significant fibrosis in NAFLD were significantly correlated only with increased arterial stiffness in subjects without hypertension or diabetes mellitus after adjustment for the above-mentioned risk factors.CAP-defined NAFLD and LSM-defined significant fibrosis in NAFLD showed significant and independent relationships with increased arterial stiffness even after adjustment for conventional cardiovascular risk factors, which can be conducive to stratifying relative risk of subjects having undergone screening assessment for cardiovascular disease.

A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature.

Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.

Thymosin beta4 induces endothelial progenitor cell migration via PI3K/Akt/eNOS signal transduction pathway.

Thymosin beta4, a G-actin-sequestering peptide, has been shown to play an important role in cell migration. However, little is known about the effect of thymosin beta4 on circulating endothelial progenitor cell (EPC) directional migration, which is essential for EPC-mediated reendothelialization and neovascularization. In our study, using a transwell migration assay, we showed that thymosin beta4 induced EPC migration in a concentration-dependent manner. Western blot analysis revealed that treatment of EPCs with thymosin beta4 resulted in a time and concentration-dependent phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinase (ERK)1/2. Functional analysis showed that thymosin beta4-induced EPC migration was blocked by phosphatidylinositol 3-kinase inhibitors (LY294002 or wortmannin) or eNOS inhibitor (Nomega-nitro-L-arginine methyl ester) but was not significantly attenuated by mitogen-activated protein kinase (MAPK)/ERK inhibitor (PD98059). These findings suggest that thymosin beta4 stimulates EPC directional migration via phosphatidylinositol 3-kinase/Akt/eNOS, rather than via MAPK/ERK signal transduction pathway.

[Effects of mixed cypermethrin and methylparathion on endocrine hormone levels and immune functions in rats: II. Interaction].

OBJECTIVE: To study interaction of mixed pesticides cypermethrin and methyl parathion on reproductive hormones, thyroid hormones, and immune functions in rats. METHODS: Eighty 2-month old Wistar rats (40 male and 40 female) were divided randomly by body weight into 8 groups. The dose 1/30 LD50 were chosen for the single or combined exposure representing respective doses of 0, cypermethrin 8.0 mg/kg bw, methylparathion 0.23 mg/kg bw, and 1/30 LD50 cypermethrin plus 1/30 LD50 methylparathion. The control group received vehicle solvent only. All groups were force-fed every two days for 30 days. Body weight gain and organ weights were determined. Serum levels of IgG and IgA, reproductive hormones [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and testosterone], as well as the thyroid hormones [triiodothyronine (T3), tetraiodothyronine (T4), and thyroid stimulating hormone (TSH) were measured using radioimmunoassay (RIA). In addition, two immunological parameters (rate of neutrophil phagocytosis, rate of lymphocyte transformation] were being measured in blood samples. RESULTS: The most of index indicated addictive interaction, while the effects on relative weights of ovaries and adrenals, IgA and rate of lymphocyte transformation were antagonistic. It was of interest that the effect on estradiol was synergistic interaction in female rats, whereas it was addictive interaction in male rats, whose estradiol level could be increased 64.64% by cypermethrin exposure. CONCLUSION: Our results showed that exposure to cypermethrin and methyl parathion mixture at 1/30 LD50 dose had interaction on endocrine hormone levels, and immune functions in rats. Estradiol was very sensitive, the mixture can enhance estradiol level both in male and female rats.

[Effects of mixed cypermethrin and methylparathion on endocrine hormone levels and immune functions in rats: I. Dose-response relationship].

OBJECTIVE: To study dose-response relationship effects of mixed cypermethrin and methyl parathion on reproductive hormones, thyroid hormones, and immune functions in rats. METHODS: Eighty 2-month old Wistar rats (40 males and 40 females) were divided randomly by bodyweight into 4 groups. Four doses (0, 1/600 LD50, 1/135 LD50 and 1/30 LD50) were chosen for the combined exposure representing respective doses of cypermethrin 0, 0.4, 1.8 and 8.0 mg/kg body weight and of methylparathion 0, 0.0115, 0.0518 and 0.2300 mg/kg body weight. The control group received vehicle solvent only. All groups were force-fed every two days for 30 days with these dose combinations. Body weight gain and organ weights were determined. Serum levels of IgG and IgA, reproductive hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and testosterone), as well as the thyroid hormones (triiodothyronine (T3), tetraiodothyronine (T4), and thyroid stimulating hormone (TSH) were measured using radioimmunoassay (RIA). In addition, two immunological parameters (rate of neutrophil phagocytosis, rate of lymphocyte transformation) were being measured in blood samples. RESULTS: The body weight gains were similar in all 4 groups. The weights of adrenal glands in exposed rats were heavier than those in control (P < 0.05). Serum FSH and E2 levels in exposed rats were higher than those in the control group (P < 0.01). Serum TSH levels were proportionally increasing with higher pesticide doses (r(s) = 0.329, P < 0.01). Lymphocyte transformation rates in all exposed animals were lower than that of the control group (P < 0.01). To the contrary, rates of neutrophil phagocytosis in all exposure groups were higher than those of the control group (P < 0.01). Furthermore, serum IgG levels of all exposed animals were lower than that of the control (P < 0.01) and serum IgA levels in exposed females were higher than that of the control (P < 0.01). Dose-response relationships for these changes were significant (rank correlation statistics P < 0.05 or < 0.01). CONCLUSION: Our results showed that exposure to different mixtures of cypermethrin and methyl parathion disrupted the endocrine hormone levels, and immune functions in rats.