Ginsenoside Rb1 is the main predominant component in
Panax
species. In this study, an eco-friendly and convenient preparation method for ginsenoside CK has been established, and five strains of ...β-glucosidase-producing microorganisms were screened out from the soil of a
Panax notoginseng
planting field using Esculin-R2A agar.
Aspergillus niger
XD101 showed that it has excellent biocatalytic activity for ginsenosides; one of the isolates can convert ginsenoside Rb1 to CK using extracellular enzyme from the mycelium. Mycelia of
A. niger
were cultivated in wheat bran media at 30 °C for 11 days. By the removal of mycelia from cultured broth, enzyme salt fractionation by ammonium sulfate (70%, v/v) precipitation, and dialysis, sequentially, crude enzyme preparations from fermentation liquid supernatant were obtained. The enzymatic transformed Rb1 as the following pathways: Rb1→Rd→F2→CK. The optimized reaction conditions are at reaction time of 72 h, in the range of pH 4–5, and temperature of 50–60 °C. Active minor ginsenosides can be obtained by a specific bioconversion via
A. niger
XD101 producing the ginsenoside-hydrolyzing β-glucosidase. In addition, the crude enzyme can be resulted in producing ginsenoside CK via conversion of ginsenoside Rb1 at high conversion yield (94.4%). FDA generally regarded,
A.niger
as safe microorganism. Therefore, these results indicate that
A. niger
XD10 may provide an alternative method to prepare ginsenoside CK without food safety issues in the pharmaceutical industry.
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•Overview of fundamental characterization of exopolysaccharides from Lactobacillus plantarum.•Summing the bioactivities of exopolysaccharides from Lactobacillus plantarum.•Revealing ...the relations between structure and function of exopolysaccharides from Lactobacillus plantarum.•Underlying the genetic organization and function of exopolysaccharides biosynthesis genes in Lactobacillus plantarum.
Lactobacillus plantarum strains have been widely used in food processing and preservation, and capability of their production of exopolysaccharides (EPSs) contributes significantly to the improvement of food quality and function. During the last decade, rapid development and accumulation of data in the research field of EPSs produced by L. plantarum have been observed. Availability of complete genome sequences from forty-three L. plantarum strains to date has provided good basis for deep analysis and understanding of the molecular and functional properties of the EPSs. In this review, an overview of the main insights into the fundamental molecular and genetic aspects of the EPSs produced by L. plantarum was presented. The organization and function of the EPS biosynthesis gene clusters from the forty-three L. plantarum strains were analyzed and compared, including those in both the genomes in thirty-six strains and plasmids in seven strains that were not reported earlier.
This study investigated the effect of exopolysaccharide (EPS) produced by Lactobacillus plantarum YW11 on the oxidative status and gut microbiota in an aging mouse model induced with d-galactose. The ...in vitro assay of the antioxidant activity of the EPS showed concentration-dependent (0.25–3.0 mg/mL) activities. At 3.0 mg/mL, the EPS reached the highest scavenging activities with half maximal inhibitory concentration values against hydroxyl radicals at 75.10% and 1.22 mg/mL, superoxide anion at 62.71% and 1.54 mg/mL, 2, 2-diphenyl-1-picrylhydrazyl at 35.11% and 0.63 mg/mL, and the maximal chelating rate on ferrous ion and the half-maximal chelating concentration of the EPS at 41.09% and 1.07 mg/mL, respectively. High doses of EPS (50 mg/kg per day) effectively relieved the oxidative stress in the aging mice with increased levels of glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity in mice serum by 21.55, 33.14, 61.09, and 38.18%, respectively, and decreased malondialdehyde level from 11.69 to 5.89 mmol/mL compared with those in the untreated aging mice model. The analysis of pyrosequencing sequence data from the gut microbiota revealed that the EPS could recover the microbiota diversity and phylotypes decreased or eliminated by the d-galactose treatment. The EPS could selectively decrease the abundance of Flexispira (37.5 fold), and increase the abundance of Blautia (36.5 fold) and Butyricicoccus (9.5 fold), which correspondingly decreased the content of nitrogen oxides to 9.87% and increased the content of short-chain fatty acids by 2.23 fold, thereby improving the oxidative and health conditions of the host intestinal tract. Further correlation analysis of core-microbiota variation induced by different treatments showed a strong correlation with oxidative phenotypes catalase, goodness of prediction (Q2) = 0.49; total antioxidant capacity, Q2 = 0.45; nitrogen oxides, Q2 = 0.67; short-chain fatty acids, Q2 = 0.55. The fermented milk with L. plantarum YW11 containing EPS also showed favorable antioxidant and gut microbiota regulating activities. The present finding provided new insights into the functional mechanism of probiotics bioactivity.
Metformin is a widely used drug in patients with type 2 diabetes mellitus. Metformin inhibits hepatic gluconeogenesis and increases glucose utilization in peripheral tissues. In recent years, several ...studies have shown that metformin is a potential therapeutic agent against cancer, alone or combined with other anticancer treatments. Metformin mainly activates the AMPK complex and regulates intracellular energy status, inhibiting the mitochondrial respiratory chain complex I and reducing the production of reactive oxygen species. Other anticancer targets of metformin are specific transcription factors inhibiting cell proliferation, promoting apoptosis and reducing drug resistance. In addition, metformin modulates tumor cells' response to anticancer treatments, favoring the activity of T cells. In diabetic patients, metformin reduces the occurrence of cancer and improves the prognosis and efficacy of anticancer treatments. In this review, we provided a comprehensive perspective of metformin as an anticancer drug.
CHD8,
which encodes Chromodomain helicase DNA-binding protein 8, is one of a few well-established Autism Spectrum Disorder (ASD) genes. Over 60 mutations have been reported in subjects with variable ...phenotypes, but little is known concerning genotype–phenotype correlations. We have identified four novel de novo mutations in Chinese subjects: two nonsense variants (c.3562C>T/p.Arg1188X, c.2065C>A/p.Glu689X), a splice site variant (c.4818-1G>A) and a missense variant (c.3502T>A/p.Tyr1168Asn). Three of these were identified from a 445-member ASD cohort by ASD gene panel sequencing of the 96 subjects who remained negative after molecular testing for copy number variation, Rett syndrome, FragileX and tuberous sclerosis complex (TSC). The fourth (p.Glu689X) was detected separately by diagnostic trio exome sequencing. We used diagnostic instruments and a comprehensive review of phenotypes, including prenatal and postnatal growth parameters, developmental milestones, and dysmorphic features to compare these four subjects. In addition to autism, they also presented with prenatal onset macrocephaly, intellectual disability, overgrowth during puberty, sleep disorder, and dysmorphic features, including broad forehead with prominent supraorbital ridges, flat nasal bridge, telecanthus and large ears. For further comparison, we compiled a comprehensive list of
CHD8
variants from the literature and databases, which revealed constitutive and somatic truncating variants in the HELIC (Helicase-C) domain in ASD and in cancer patients, respectively, but not in the general population. Furthermore, HELIC domain mutations were associated with a severe phenotype defined by a greater number of clinical features, lower verbal IQ, and a prominent, consistent pattern of overgrowth as measured by weight, height and head circumference. Overall, this study adds to the ASD-associated loss-of-function mutations in
CHD8
and highlights the clinical importance of the HELIC domain of CHD8.
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Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can ...decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin’s effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast. The interaction between SIRT6 and NF-κB is highly important in osteoblast differentiation just as the relationship between OPG and RANKL in the process of bone formation. During differentiation, we show that SIRT6 inhibits phosphorylation of NF-κB and that OPG increases while RANKL decrease in HG groups. In addition, ablation of sirt6 in mice causes phosphorylation of NF-κB at high-levels and RANKL increases slightly in femur bone cells. However, other bone formation marker proteins such as RUNX2, OSTERIX and OPG appear at low-levels in sirt6 KO mice. It has been confirmed that downregulation of OCT4 is critical incident in the differentiation of embryonic stem cells. Fortunately, we observe that SIRT6 can suppress OCT4 expression in murine preosteoblast and the expression of OCT4 is at high-level in sirt6 KO mice. Taken together, this study’s results illuminate metformin’s effect on bone metabolism under HG condition and help to elucidate why metformin can promote bone fracture healing of patients with T2DM.
Ice-sheet development in Antarctica was a result of significant and rapid global climate change about 34 million years ago. Ice-sheet and climate modelling suggest reductions in atmospheric carbon ...dioxide (less than three times the pre-industrial level of 280 parts per million by volume) that, in conjunction with the development of the Antarctic Circumpolar Current, led to cooling and glaciation paced by changes in Earth's orbit. Based on the present subglacial topography, numerical models point to ice-sheet genesis on mountain massifs of Antarctica, including the Gamburtsev mountains at Dome A, the centre of the present ice sheet. Our lack of knowledge of the present-day topography of the Gamburtsev mountains means, however, that the nature of early glaciation and subsequent development of a continental-sized ice sheet are uncertain. Here we present radar information about the base of the ice at Dome A, revealing classic Alpine topography with pre-existing river valleys overdeepened by valley glaciers formed when the mean summer surface temperature was around 3 °C. This landscape is likely to have developed during the initial phases of Antarctic glaciation. According to Antarctic climate history (estimated from offshore sediment records) the Gamburtsev mountains are probably older than 34 million years and were the main centre for ice-sheet growth. Moreover, the landscape has most probably been preserved beneath the present ice sheet for around 14 million years.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Baker, Gordon et al. present the first international case series describing the neurodevelopmental disorder associated with Synaptotagmin 1 (SYT1) de novo missense mutations. Key features include ...movement abnormalities, severe intellectual disability, and hallmark EEG alterations. Expression of patients' SYT1 mutations in mouse neurons disturbs presynaptic vesicle dynamics in a mutation-specific manner.
Abstract
Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1.
Addition of probiotics to yogurt with desired health benefits is gaining increasing attention. To further understand the effect of probiotic
on the quality and function of fermented milk, probiotic ...fermented milk (PFM) made with probiotic
K25 and yogurt starter (
ssp.
and
) was compared with the control fermented milk (FM) made with only the yogurt starter. The probiotic strain was shown to survive well with a viable count of 7.1 ± 0.1 log CFU/g in the PFM sample after 21 days of storage at 4°C. The strain was shown to promote formation of volatiles such as acetoin and 2,3-butanediol with milk fragrance, and it did not cause post-acidification during refrigerated storage. Metabolomics analysis by GC-MS datasets coupled with multivariate statistical analysis showed that addition of
K25 increased formation of over 20 metabolites detected in fermented milk, among which γ-aminobutyric acid was the most prominent. Together with several other metabolites with relatively high levels in fermented milk such as glyceric acid, malic acid, succinic acid, glycine, alanine, ribose, and 1,3-dihydroxyacetone, they might play important roles in the probiotic function of
K25. Further assay of the bioactivity of the PFM sample showed significant (
< 0.05) increase of ACE inhibitory activity from 22.3% at day 1 to 49.3% at day 21 of the refrigerated storage. Therefore, probiotic
K25 could be explored for potential application in functional dairy products.
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