Tailored pharmacist-led intervention to improve adherence to Iron supplementation in premature infants: a randomized controlled trial in China.

Introduction: Prematurity is due to a number of factors, especially genetics. This study was designed to evaluate the impact of a pharmacist-led patient-centered medication therapy management trial on iron deficiency and medication adherence among premature infants receiving iron supplementation at a tertiary hospital in Shaoxing, China. Methods: In this randomised controlled trial, eighty-one premature infants, with or without genetic factors, born at 26 to 30 weeks and 6 days gestational age, will be recruited and randomised to an intervention group or a control group. The intervention group will receive a pharmacist-driven discharge counseling on iron supplements from recruitment, until 12 months. The control group will receive care as usual. The main outcomes were haemoglobin (g/L), serum iron (µg/L), medication adherence estimation and differentiation scale, the satisfaction with information about medicines scale, beliefs about medicines questionnaire and the Bayley scales for infant development. Results: A total of 81 patients were enrolled in the study. After intervention, results for the haemoglobin and serum iron differed significantly between the control group and the intervention group (101.36 vs. 113.55, P < 0.0001 and 51.13 vs. 101.36, P = 0.004). Additionally, there was a substantial difference between the intervention group and the control group in terms of patient medication adherence estimation and differentiation scale (27 vs. 34, P = 0.0002). the intervention group had better mental development index and psychomotor development index, compared with the control group (91.03 vs. 87.29, P = 0.035 and 95.05 vs. 90.00, P = 0.022). Discussion: In premature infants with iron deficiency, our pharmacist-led team significantly improved clinical outcomes and medication adherence.

Activation of ULK1 to trigger FUNDC1-mediated mitophagy in heart failure: Effect of Ginsenoside Rg3 intervention.

BACKGROUND: Although the development of therapies for heart failure (HF) continues apace, clinical outcomes are often far from ideal. Unc51-like-kinase 1 (ULK1)-mediated mitophagy prevents pathological cardiac remodeling and heart failure (HF). Molecularly ULK1-targeted agent to enhance mitophagy is scanty. HYPOTHESIS/PURPOSE: This study aimed to investigate whether Ginsenoside Rg3 (Rg3) can activate ULK1 to trigger FUNDC1-mediated mitophagy for protecting heart failure. METHODS: Molecular docking and surface plasmon resonance were used to detect the ULK1 binding behavior of Rg3. Established HF model in rats and transcriptome sequencing were used to evaluate the therapeutic effect and regulatory mechanism of Rg3. Loss-of-function approaches in vivo and in vitro were performed to determine the role of ULK1 in Rg3-elicited myocardial protection against HF. FUNDC1 recombinant plasmid of site mutation was applied to elucidate more in-depth mechanisms. RESULTS: Structurally, a good binding mode was unveiled between ULK1 and Rg3. In vivo, Rg3 improved cardiac dysfunction, adverse remodeling, and mitochondrial damage in HF rats. Furthermore, Rg3 promoted Ulk1-triggered mitophagy both in vivo and in vitro, manifested by the impetus of downstream Fundc1-Lc3 interaction. Of note, the protective effects conferred by Rg3 against mitophagy defects, pathological remodeling, and cardiac dysfunction were compromised by Ulk1 gene silencing both in vivo and in vitro. Mechanistically, Rg3 activated mitophagy by inducing ULK1-mediated phosphorylation of FUNDC1 at the Ser17 site, not the Ser13 site. CONCLUSION: Together these observations demonstrated that Rg3 acts as a ULK1 activator for the precise treatment of HF, which binds to ULK1 to activate FUNDC1-mediated mitophagy.

Reduction of phonetic mismatch negativity may depict illness course and predict functional outcomes in schizophrenia.

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes.

Endophytic Bacteria as Contributors to Theanine Production in Camellia sinensis.

Theanine is the most abundant non-protein amino acid in Camellia sinensis, but it is not known how a tea plant accumulates such high levels of theanine. The endophyte isolated from in vitro grown plantlets of C. sinensis cultivars was identified as Luteibacter spp., showing strong biocatalytic activity for converting both glutamine and ethylamine to theanine. Theanine was secreted outside of the bacteria. The endophyte isolated from in vitro plantlets of Camellia oleifera cultivar was identified as Bacillus safensis and did not convert glutamine and ethylamine to theanine. Enzymatic assays in vitro indicated that γ-glutamyltranspeptidases rCsEGGTs from the endophyte Luteibacter strains converted glutamine and ethylamine to theanine at higher rates than rCsGGTs from C. sinensis. This is the first report on theanine biosynthesis by an endophyte from C. sinensis, which provides a new pathway to explore the mechanism of theanine biosynthesis in C. sinensis and the interactions between an endophyte and tea plants.

The tea plant reference genome and improved gene annotation using long-read and paired-end sequencing data.

Tea is a globally consumed non-alcohol beverage with great economic importance. However, lack of the reference genome has largely hampered the utilization of precious tea plant genetic resources towards breeding. To address this issue, we previously generated a high-quality reference genome of tea plant using Illumina and PacBio sequencing technology, which produced a total of 2,124 Gb short and 125 Gb long read data, respectively. A hybrid strategy was employed to assemble the tea genome that has been publicly released. We here described the data framework used to generate, annotate and validate the genome assembly. Besides, we re-predicted the protein-coding genes and annotated their putative functions using more comprehensive omics datasets with improved training models. We reassessed the assembly and annotation quality using the latest version of BUSCO. These data can be utilized to develop new methodologies/tools for better assembly of complex genomes, aid in finding of novel genes, variations and evolutionary clues associated with tea quality, thus help to breed new varieties with high yield and better quality in the future.

Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality.

Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to ∼0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred ∼30 to 40 and ∼90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.

A genome-wide analysis of the lysophosphatidate acyltransferase (LPAAT) gene family in cotton: organization, expression, sequence variation, and association with seed oil content and fiber quality.

BACKGROUND: Lysophosphatidic acid acyltransferase (LPAAT) encoded by a multigene family is a rate-limiting enzyme in the Kennedy pathway in higher plants. Cotton is the most important natural fiber crop and one of the most important oilseed crops. However, little is known on genes coding for LPAATs involved in oil biosynthesis with regard to its genome organization, diversity, expression, natural genetic variation, and association with fiber development and oil content in cotton. RESULTS: In this study, a comprehensive genome-wide analysis in four Gossypium species with genome sequences, i.e., tetraploid G. hirsutum- AD1 and G. barbadense- AD2 and its possible ancestral diploids G. raimondii- D5 and G. arboreum- A2, identified 13, 10, 8, and 9 LPAAT genes, respectively, that were divided into four subfamilies. RNA-seq analyses of the LPAAT genes in the widely grown G. hirsutum suggest their differential expression at the transcriptional level in developing cottonseeds and fibers. Although 10 LPAAT genes were co-localised with quantitative trait loci (QTL) for cottonseed oil or protein content within a 25-cM region, only one single strand conformation polymorphic (SSCP) marker developed from a synonymous single nucleotide polymorphism (SNP) of the At-Gh13LPAAT5 gene was significantly correlated with cottonseed oil and protein contents in one of the three field tests. Moreover, transformed yeasts using the At-Gh13LPAAT5 gene with the two sequences for the SNP led to similar results, i.e., a 25-31% increase in palmitic acid and oleic acid, and a 16-29% increase in total triacylglycerol (TAG). CONCLUSIONS: The results in this study demonstrated that the natural variation in the LPAAT genes to improving cottonseed oil content and fiber quality is limited; therefore, traditional cross breeding should not expect much progress in improving cottonseed oil content or fiber quality through a marker-assisted selection for the LPAAT genes. However, enhancing the expression of one of the LPAAT genes such as At-Gh13LPAAT5 can significantly increase the production of total TAG and other fatty acids, providing an incentive for further studies into the use of LPAAT genes to increase cottonseed oil content through biotechnology.

Metabonomics study of the effects of pretreatment with glycyrrhetinic acid on mesaconitine-induced toxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debx. (Fuzi), a commonly use traditional Chinese medicine (TCM), has often been used in combination with Rhizoma Glycyrrhizae (Gancao) to reduce its toxicity due to diester diterpenoid alkaloids aconitine, mesaconitine, and hypaconitine. However, the mechanism of detoxication is still unclear. Glycyrrhetinic acid (GA) is the metabolite of glycyrrhizinic acid (GL), the major component of Gancao. In present study, the effect of GA on the changes of metabolic profiles induced by mesaconitine was investigated using NMR-based metabolomic approaches. MATERIALS AND METHODS: Fifteen male Wistar rats were divided into a control group, a group administered mesaconitine alone, and a group administered mesaconitine with one pretreatment with GA. Their urine samples were used for NMR spectroscopic metabolic profiling. Statistical analyses such as orthogonal projections to latent structures-discriminant analysis (OPLS-DA), t-test, hierarchical cluster, and pathway analysis were used to detect the effects of pretreatment with GA on mesaconitine-induced toxicity. RESULTS: The OPLS-DA score plots showed the metabolic profiles of GA-pretreated rats apparently approach to those of normal rats compared to mesaconitine-induced rats. From the t-test and boxplot results, the concentrations of leucine/isoleucine, lactate, acetate, succinate, trimethylamine (TMA), dimethylglycine (DMG), 2-oxo-glutarate, creatinine/creatine, glycine, hippurate, tyrosine and benzoate were significantly changed in metabolic profiles of mesaconitine-induced rats. The disturbed metabolic pathways include amino acid biosynthesis and metabolism. CONCLUSIONS: GA-pretreatment can mitigate the metabolic changes caused by mesaconitine-treatment on rats, indicating that prophylaxis with GA could reduce the toxicity of mesaconitine at the metabolic level.

[Clinical analysis and follow-up of neonatal purulent meningitis caused by group B streptococcus].

OBJECTIVE: To study the clinical characteristics, antibiotics sensitivity and outcome of group B streptococcus (GBS) meningitis in neonates in order to provide the guide for early diagnosis and appropriate treatment. METHOD: A retrospective review was performed and a total of 13 cases of neonatal purulent meningitis caused by GBS were identified in the Neonatal Intensive Care Unit of Yuying Children's Hospital of Wenzhou Medical University from January 1, 2005 to May 31, 2013. The clinical characteristics, antibiotics sensitivity test results and outcome were analyzed. RESULT: Fever, poor feeding, seizure and lethargy were common clinical signs of neonatal purulent meningitis caused by GBS. Three cases of early onset GBS meningitis received prepartum antibiotics. All 13 cases had abnormal C-reactive protein (CRP) level, and 11 cases had increased CRP within hours after admission. Of the 13 patients, 7 were cured, 4 discharged with improvement, 2 patients died during hospitalization after being given up because of serious complication. The average length of stay for recovered patients was (47 ± 21)d. Acute complications mainly included hyponatremia (5 cases), intracranial hemorrhage (3 cases) , ventriculomegaly (3 cases) , subdural collection (2 cases) , hydrocephalus (2 cases), septic shock (2 cases), cerebral hernia (1 case), encephalomalacia (1 case). One preterm patient with early onset GBS meningitis died 1 month after hospital discharge. Among 7 survivors with 10-24 months follow-up, 3 were early onset GBS meningitis, 2 with normal results of neurologic examination, 1 with delayed motor development, 4 were late onset GBS meningitis, 1 with normal results of neurologic examination, 3 were neurologically impaired with manifestations including delayed motor development (2 cases) and seizures (1 case). All the GBS strains were sensitive to penicillin and linezolid (13/13, 10/10), the susceptibility to levofloxacin, ampicillin and vancomycin were 11/12, 9/10, 8/13 respectively. CONCLUSION: The clinical manifestations of neonatal purulent meningitis caused by GBS are usually non-specific. It is associated with long hospitalization, neurological impairments and sequelae. Monitoring of serum CRP level is valuable for early diagnosis. Antepartum prophylaxis, early diagnosis and therapy are vital. Large dose penicillin is the priority choice to treat the neonatal purulent meningitis caused by GBS, linezolid should be used in intractable cases.

Metabolomic analysis of biofluids from rats treated with Aconitum alkaloids using nuclear magnetic resonance and gas chromatography/time-of-flight mass spectrometry.

The Aconitum alkaloids aconitine, mesaconitine, and hypaconitine are the main toxic components in a commonly used traditional Chinese herbal medicine Fu Zi. To provide guidelines for the safe use of this medicine, metabolic changes in Wistar rats caused by these compounds were investigated by means of integrated analysis of two metabonomic approaches: (1)H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Rats were given a single dose of aconitine, mesaconitine, hypaconitine, or vehicle. The largest metabolic changes were observed 6 h after treatment. Every group receiving a dose had higher urine concentrations of glucose, acetate, dimethylglycine, succinate, and alanine and had lower concentrations of creatinine, citrate, 2-oxoglutarate, N-acetylated metabolites, and trimethylamine-N-oxide (TMAO) than did the control group. These results may reflect the perturbation of renal tubular function within the first 24 h after treatment. The results also revealed a larger perturbation of metabolic profiles in the aconitine group than in the mesaconitine and hypaconitine groups, illustrating how these alkaloids exhibit different toxicities. An analysis of plasma samples collected 7 days postdose showed that there were higher levels of lactate, alanine, and lipids along with lower levels of glucose, beta-hydroxybutyrate, and creatine in the plasma of the aconitine and mesaconitine groups than there were in the control and hypaconitine groups. The GC/TOF-MS data from the plasma samples showed that the number of metabolites, with significant changes or with a tendency to change, in the aconitine and mesaconitine groups were dissimilar, suggesting a possible difference in the acute toxicity mechanisms of these alkaloids.

[Effect of Tianwang Buxin decoction or Tianwang Buxin without Radix platycodi decoction on brain neurotransmitter of rats hyposomnia model].

OBJECTIVE: To understand the action mechanism of Tianwang Buxin decoction that is the whole prescription included all drugs from Tianwang Buxin honeyed pill and Tianwang Buxin without radix platycodi decoction on the nerves-calming and hyposomnia-curing. METHOD: The influence of Tianwang Buxin decoction and Tianwang Buxin without radix platycodi decoction on somnus utilizing the mice' s somnus in coordination with Pentobarbital sodium was observed. Investigation whether the compatibility of radix platycodi affect the concentration of brain neurotransmitter, 5-HT, NA and DA, correlated sleep-awareness by HPLC-ECD detection was carried out after rats' hyposomnia model were founded. RESULT: The falling asleep rates of mice given subthreshold dose raised (P<0.05), remarkably because of Tianwang Buxin decoction. But there is significant difference with Tianwang Buxin lack of radix platycodi decoction despite the heightening tendency. All groups were discovered that the level of 5-HT and 5-HIAA, the monoamine transmitter, heighten obviously after the whole prescription and the prescription without radix platycodi were administered in nuclei raphae medullae oblongatae (P<0.05), but it is only the whole prescription group that emerged same phenomenon in the Ammon's horn and striatum area. Furthermore significant difference exist as comparing Tianwang Buxin whole prescription decoction with Tianwang Buxin without radix platycodi decoction. The level of another monoamine transmitter DA stepped up notably in the whole prescription and the prescription without radix platycodi groups following administration in corpora striata (P<0.05). CONCLUSION: The mechanism of hypnosis action lie in enhancement of releasing 5-HT in encephalic regions for the Tianwang Buxin whole prescription decoction, but it's possible that radix platycodi may be the key point that adjusts the additional quantity.