Cryptochrome PtCPF1 regulates high temperature acclimation of marine diatoms through coordination of iron and phosphorus uptake.

Increasing ocean temperatures threaten the productivity and species composition of marine diatoms. High temperature response and regulation are important for the acclimation of marine diatoms to such environments. However, the molecular mechanisms behind their acclimation to high temperature are still largely unknown. In this study, the abundance of PtCPF1 homologs (a member of the cryptochrome-photolyase family in the model diatom Phaeodactylum tricornutum) transcripts in marine phytoplankton is shown to increase with rising temperature based on Tara Oceans datasets. Moreover, the expression of PtCPF1 in P. tricornutum at high temperature (26 °C) was much higher than that at optimum temperature (20 °C). Deletion of PtCPF1 in P. tricornutum disrupted the expression of genes encoding two phytotransferrins (ISIP2A and ISIP1) and two Na+/P co-transporters (PHATRDRAFT_47667 and PHATRDRAFT_40433) at 26 °C. This further impacted the uptake of Fe and P, and eventually caused the arrest of cell division. Gene expression, Fe and P uptake, and cell division were restored by rescue with the native PtCPF1 gene. Furthermore, PtCPF1 interacts with two putative transcription factors (BolA and TF IIA) that potentially regulate the expression of genes encoding phytotransferrins and Na+/P co-transporters. To the best of our knowledge, this is the first study to reveal PtCPF1 as an essential regulator in the acclimation of marine diatoms to high temperature through the coordination of Fe and P uptake. Therefore, these findings help elucidate how marine diatoms acclimate to high temperature.

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1-Nrf2 Signaling Pathway and Regulating Gut Microbiota.

Inflammatory bowel disease (IBD), with increasing incidence, causes a range of gastrointestinal symptoms and brings distress and impact on the health and lives of patients. The aim of this study was to explore the protective effects of industrially produced rice protein peptides (RPP) on dextran sulfate sodium (DSS)-induced acute colitis in mice and the potential mechanisms. The results showed that RPP treatment alleviated the symptoms of colitis in mice, including weight loss, colon shortening, and injury, decreased the level of disease activity index (DAI), regulated the balance of inflammatory factors and oxidation, activated Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, regulated the expression of related antioxidant proteases, and promoted the expression of intestinal tight junction proteins. In addition, RPP maintained intestinal mucosal barrier function and alleviated acute colitis caused by DSS treatment in mice by increasing the value of F/B, increasing the relative abundance of beneficial bacteria such as Akkermansia, and regulating the level of short-chain fatty acids. In conclusion, RPP alleviated colitis symptoms through the Keap1-Nrf2 signaling pathway and regulating gut microbiota, which had the potential as dietary supplements or functional foods.

Janus-like Bx C/C Quantum Sheets with Z-Scheme Mechanism Strengthen Tumor Photothermal-Immunotherapy in NIR-II Biowindow.

Carbon dots (CDs) are one of the most popular photothermal agents (PTAs) as a noninvasive strategy for tumor treatment. However, because of the inherent dominant fluorescent emission, the CDs-based PTAs hardly achieve a single photothermal conversion, which causes low photothermal conversion efficiency and poor photothermal performance. In this regard, finding a new CDs-based material system to greatly restrain its fluorescence to enhance its photothermal conversion efficiency is highly required, however, it is still a grand challenge. Herein, a kind of Z-scheme CDs-based PTAs consisting of 2D ultrathin nonmetallic Bx C/C Janus quantum sheets (Bx C/C JQSs) is reported to greatly enhance the photothermal conversion efficiency. It is demonstrated that the heterogeneous growth of Z-scheme Bx C/C JQSs enables the NIR-driven quick injection of hot electrons from C into the conjugated Bx C, realizing a single conversion of light to heat, and resulting in a high photothermal conversion of 60.0% in NIR-II. Furthermore, these new Z-scheme Bx C/C-polyethylene glycol JQSs display outstanding biocompatibility and show effective tumor elimination outcome both in vitro and in vivo through the synergistic photothermal-immunotherapy in the NIR-II biowindow with undetectable harm to normal tissues.

Herbal Compatibility of Ginseng and Rhubarb Exerts Synergistic Neuroprotection in Cerebral Ischemia/Reperfusion Injury of Rats.

OBJECTIVE: Ischemic stroke is a complex multifactorial disease caused by interactions among polygenetic, environmental, and lifestyle factors with limited effective treatments. Multi-herbal formulae have long been used for stroke through herbal compatibility in traditional Chinese medicine (TCM); however, there is still a lack of evidence due to their unimaginable complexity. Herbal pairs represent the simplest and basic features of multi-herbal formulae, which are of great significance in clarifying herbal compatibility. Here, we aim to investigate the neuroprotective effects of the herbal compatibility of Ginseng and Rhubarb on a cerebral ischemia/reperfusion (I/R) injury model of rats. METHODS: Male adult SD rats were randomly divided into a sham group, a normal saline (NS) group, a Ginseng group, a Rhubarb group, and a Ginseng + Rhubarb (GR) group, a Carbenoxolone [CBX, gap junction (GJ) specific inhibitor] group, and a GR + CBX group. Each group was further assigned into four subgroups according to ischemic time (6 h, 1 day, 3 days, and 7 days). The cerebral I/R injury model was established according to the modified Zea Longa method. The Neurological Deficiency Score (NDS) was assessed by the Zea-Longa scale; the cerebral infarction area was detected by TTC (2,3,5-triphenyltetrazolium chloride) staining; and the expression of connexin-43 (Cx43) and aquaporin-4 (AQP4) were detected based on an immunofluorescence technique and quantitative real-time-PCR. RESULTS: Compared to the I/R group, both the independent and combined use of Ginseng and Rhubarb can significantly improve NDS (P < 0.05), decrease the percentage of the cerebral infarction area around the infarction penumbra (P < 0.05) and down-regulate the expression of Cx43 and AQP4 after I/R injury (P < 0.05). The GR had more significant effects than that of Ginseng and Rhubarb (P < 0.05). Compared with the GR group, the GR + CBX group significantly improved in NDS (P < 0.05), and decreased the percentage of the cerebral infarction area (P < 0.05) and expression of Cx43 and AQP4 protein (P < 0.05). CONCLUSION: The herbal compatibility of Ginseng and Rhubarb synergistically exerts neuroprotective function during acute cerebral I/R injury, mainly through reducing the expression of Cx43 and AQP4.

Integration of cascade delivery and tumor hypoxia modulating capacities in core-releasable satellite nanovehicles to enhance tumor chemotherapy.

Drug nanovehicles owning tumor microenvironment responsive and modulating capacities are highly demanding for effective tumor chemotherapy but still lack of exploration. Here, a kind of core-releasable satellite nanovehicles was rational constructed, which is composed of polydopamine (PDA) cores as photothermal agents and the carrier for small satellite nanoparticles (NPs) and drugs, G5Au NPs as the drug-loading satellites for deep tumor drug delivery and as catalase-like agents for relieving tumor hypoxia, doxorubicin (DOX) as the model chemotherapeutic drug loaded by both PDA and G5Au NPs, and polyethylene glycol (PEG) shells to improve biosafety. The developed drug-loaded nanovehicles (denoted as PDA-G5Au-PEG@DOX) can release G5Au satellites and DOX in stimuli-responsive manners. Thorough drug delivery in solid tumor can be realized via transporting DOX to the near-by area of and remote area from blood vessels by PDA and G5Au, respectively. Monitored by photoacoustic imaging and near-infrared fluorescence imaging, these PDA-G5Au-PEG@DOX NPs could accumulate in 4T1 tumor effectively. Under this guidance, significant tumor growth suppression could be achieved by the treatment of PDA-G5Au-PEG@DOX NPs plus laser without detectable side effects during the treatment period. The developed drug-loaded core-satellite nanovehicles with tumor microenvironment responsive/modulating capacities are of great potential in precise tumor treatments.

The reporting quality of acupuncture for neurogenesis in experimental ischemic stroke study.

BACKGROUND: There is increasing evidence demonstrating the highly inadequate reporting of preclinical research in multiple scientific publications. The purpose of this study is to systematically investigate the reporting quality of acupuncture for neurogenesis in animal models of acute ischemic stroke. METHODS: We searched eight databases, including PubMed, EMBASE, CINAHL, AMED, Chinese National Knowledge Infrastructure, VIP information database, Wanfang data Information Site, and Chinese Biomedical Literature Database. The methodological quality of included studies was assessed by using the CAMARADES 10-item checklist. The STRICTA statement was modified to gear to animal acupuncture research. The reporting quality was assessed according to the ARRIVE guidelines and the modified STRICTA statement. Data were analyzed with descriptive statistics. RESULTS: Ultimately, 44 studies containing 2,411 subjects were identified. The overall compliance with the CAMARADES 10-item checklist has a mean of 4.3. The reporting quality indicated that the overall compliance with ARRIVE guidelines has a mean of 59.9% and with the modified STRICTA statement a mean of 71.8%. The findings suggest that the reporting quality of acupuncture for preclinical stroke was generally poor. CONCLUSIONS: Full compliance with ARRIVE guidelines and/or modified STRICTA statement in designing, conducting and reporting preclinical acupuncture research is urgently needed in the future.

Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.

Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways.

Sham Electroacupuncture Methods in Randomized Controlled Trials.

Sham electroacupuncture (EA) control is commonly used to evaluate the specific effects of EA in randomized-controlled trials (RCTs). However, establishing an inert and concealable sham EA control remains methodologically challenging. Here, we aimed to systematically investigate the sham EA methods. Eight electronic databases were searched from their inception to April 2015. Ten out of the 17 sham EA methods were identified from 94 RCTs involving 6134 participants according to three aspects: needle location, depth of needle insertion and electrical stimulation. The top three most frequently used types were sham EA type A, type L and type O ordinally. Only 24 out of the 94 trials reported credibility tests in six types of sham EA methods and the results were mainly as follows: sham EA type A (10/24), type B (5/24) and type Q (5/24). Compared with sham EA controls, EA therapy in 56.2% trials reported the specific effects, of which the highest positive rate was observed in type N (3/4), type F (5/7), type D (4/6) and type M (2/3). In conclusion, several sham EA types were identified as a promising candidate for further application in RCTs. Nonetheless, more evidence for inert and concealable sham EA control methods is needed.

The quality of reporting of randomized controlled trials of electroacupuncture for stroke.

BACKGROUND: Electroacupuncture (EA), as an extension technique of acupuncture based on traditional acupuncture combined with modern electrotherapy, is commonly used for stroke in clinical treatment and researches. However, there is still a lack of enough evidence to recommend the routine use of EA for stroke. This study is aimed at evaluating the quality of reporting of randomized controlled trials (RCTs) on EA for stroke. METHODS: RCTs on EA for stroke were evaluated by using CONSORT guidelines and STRICTA guidelines. Microsoft Excel 2010 and the R software were used for descriptive statistics analyses. RESULTS: Seventy studies involving 5468 stroke patients were identified. The CONSORT scores ranged from 16.2 to 67.6% and STRICTA scores from 29.4 to 82.4%. The central items in CONSORT as eligibility criterion, sample size calculation, primary outcome, method of randomization sequence generation, allocation concealment, implementation of randomization, description of blinding, and detailed statistical methods were reported in 100, 6, 68, 37, 14, 10, 16, and 97% of trials, respectively. The reporting of items in STRICTA as acupuncture rationale was 1a (91%), 1b (86%) and 1c 0%; needling details 2a (33%), 2b (97%), 2c (29%), 2d (64%), 2e (100%), 2f (55%) and 2 g (66%); treatment regimen 3a (69%) and 3b (100%); other components of treatment 4a (86%) and 4b (13%); practitioner background item 5 (16%); control intervention(s) 6a (93%) and 6b (10%). CONCLUSIONS: The quality of reporting of RCTs on EA for stroke was generally moderate. The reporting quality needs further improvement.

Bioactive components of Chinese herbal medicine enhance endogenous neurogenesis in animal models of ischemic stroke: A systematic analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been used to treat stroke for thousands of years. The objective of the study is to assess the current evidence for bioactive components of CHM as neurogenesis agent in animal models of ischemic stroke. METHODS: We searched PubMed, China National Knowledge Infrastructure, WanFang Database, and VIP Database for Chinese Technical Periodicals published from the inception up to November 2015. The primary measured outcome was one of neurogenesis biomarker, including Bromodeoxyuridine (BrdU), Nestin, doublecortin (DCX), polysialylated form of the neural cell adhesion molecule (PSA-NCAM), neuronal nuclear antigen (NeuN), and glial fibrillary acidic protein (GFAP). RESULTS: Thirty eligible studies were identified. The score of quality assessment ranged from 2 of 10 to 7 of 10. Compared with controls, 10 studies conducting neurobehavioral evaluation showed significant effects on bioactive components of CHM for improving neurological deficits score after ischemic insults (P < 0.01 or P < 0.05); 6 studies in Morris water-maze test showed bioactive components of CHM significantly decreased escape latency and increased residence time (P < 0.05); 5 studies demonstrated that bioactive components of CHM significantly reduced infarct volume after ischemic stroke (P < 0.05); 25 of 26 studies showed that bioactive components of CHM significantly increased the expression of BrdU and/or Nestin markers in rats/mice brain after ischemic injury (P < 0.05, or P < 0.01); 4 of 5 studies for promoting the expression of PSA-NCAM or DCX biomarker (P < 0.05); 5 studies for improving the expression of NeuN biomarker (P < 0.05); 6 of 7 studies for promoting the expression of GFAP biomarker in brain after ischemic stroke (P < 0.05). CONCLUSION: The findings suggest that bioactive components of CHM may improve neurological function, reduce infarct volume, and promote endogenous neurogenesis, including proliferation, migration, and differentiation of neural stem cells after ischemic stroke. However, evidences are supported but limited because only a few studies were available for each descriptive analysis. Further rigor study is still needed.

Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats.

Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa's scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P < 0.05). In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

A new cycloartane triterpene glycoside from Souliea vaginata.

A new cycloartane-type triterpene glycoside, namely soulieoside M (1), and one known compound, beesioside I (2), were isolated from the ethanolic extract of the rhizomes of Souliea vaginata. Their structures were determined spectroscopically and compared with previously reported spectral data. Compounds 1 and 2 were evaluated for their cytotoxic activities against three human cancer cell lines.

[Full-length cDNA cloning of flavonol synthase genes of Carthamus tinctorius and construction plant expression vector].

Flavonol synthase (FLS) is one of the key enzymes in flavonoids metabolic pathways. In this study, middle sequence was obtained from Carthamus tinctorius transcriptome sequencing results. Full-length cDNAs of FLS was cloned from petals of C. tinctorius to FLS by using RT-PCR and RACE technology. Its full-length cDNA was 1,201 bp, with an open reading frame of 1,101 bp and 336 encoded amino acids. The phylogenetic analysis showed that, FLS gene encoded amino acids in C. tinctorius were highly homologous with amino acids in congeneric Compositae species, especially Rudbeckia laciniata. The pBASTA-FLS plant expression vector was successfully built by the molecular biology method, which lays a foundation for further studying biology functions of the gene and biosynthesis mechanism of flavonoids.

RNA-Seq for gene identification and transcript profiling of three Stevia rebaudiana genotypes.

BACKGROUND: Stevia (Stevia rebaudiana) is an important medicinal plant that yields diterpenoid steviol glycosides (SGs). SGs are currently used in the preparation of medicines, food products and neutraceuticals because of its sweetening property (zero calories and about 300 times sweeter than sugar). Recently, some progress has been made in understanding the biosynthesis of SGs in Stevia, but little is known about the molecular mechanisms underlying this process. Additionally, the genomics of Stevia, a non-model species, remains uncharacterized. The recent advent of RNA-Seq, a next generation sequencing technology, provides an opportunity to expand the identification of Stevia genes through in-depth transcript profiling. RESULTS: We present a comprehensive landscape of the transcriptome profiles of three genotypes of Stevia with divergent SG compositions characterized using RNA-seq. 191,590,282 high-quality reads were generated and then assembled into 171,837 transcripts with an average sequence length of 969 base pairs. A total of 80,160 unigenes were annotated, and 14,211 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. Gene sequences of all enzymes known to be involved in SG synthesis were examined. A total of 143 UDP-glucosyltransferase (UGT) unigenes were identified, some of which might be involved in SG biosynthesis. The expression patterns of eight of these genes were further confirmed by RT-QPCR. CONCLUSION: RNA-seq analysis identified candidate genes encoding enzymes responsible for the biosynthesis of SGs in Stevia, a non-model plant without a reference genome. The transcriptome data from this study yielded new insights into the process of SG accumulation in Stevia. Our results demonstrate that RNA-Seq can be successfully used for gene identification and transcript profiling in a non-model species.

Genetic diversity of storage proteins in cultivated buckwheat.

Prolamin and albumn variations of the storage proteins in 76 cultivated buckwheat accessions (55 accessions of Fagopyrum tataricum, 21 accessions of F. esculentum) from 7 countries were characterized by A-PAGE and SDS-PAGE, respectively, for the purpose of evaluating the genetic diversity of cultivated buckwheat at the level of proteins. A total of 18 prolamin bands were detected, among which 88.89 % bands were polymorphic. The number of albumn bands based on SDS-PAGE observed in accessions ranged from 4 to 10. Most intense bands were in the range of molecular weights from 29 to 97.2 kDa. The average of genetic similarity coefficient based on prolamin bands was 0.784 (in F. tataricum and F. esculentum were 0.892 and 0.681, respectively), while on prolamin and albumn bands was 0.742 (in F. tataricum and F. esculentum were 0.864 and 0.633, respectively). Accessions of F. tataricum and F. esculentum showed significant interspecific variation in the A-PAGE and SDS-PAGE profile of the storage proteins. The cluster analysis indicated that all the accessions could be divided into 3 groups and 3 subgroups. The genetic variations among cultivated buckwheat accessions were associated with their geographic origins in some degree.