•Two polysaccharides were obtained from the mycelium and fruiting bodies.•The structural features of polysaccharides were investigated and compared.•They had a backbone of (1→4)-linked ...α-d-glucopyranosyl residues.
The structural properties of polysaccharides, respectively, obtained from the fermented mycelium and cultivated fruiting bodies of the Cordyceps militaris were investigated and compared in this paper. First, the crude polysaccharides were extracted from the mycelium and the fruiting bodies, respectively. The polysaccharides were successively purified by Sevag and chromatography on Sephadex G-100 column to produce two polysaccharides fractions termed CMPS-II and CBPS-II, respectively. The average molecular weights of CMPS-II and CBPS-II were 1.402×103kDa and 1.273×103kDa, respectively, and they were mainly composed of mannose, glucose and galactose in the mole ratios of 1:28.63:1.41 and 1:12.41:0.74, respectively, for CMPS-II and CBPS-II. Afterward, the structural features of CMPS-II and CBPS-II were investigated by a combination of chemical and instrumental analysis, such as FT-IR, periodate oxidation-Smith degradation, GC–MS, NMR and methylation analysis. The results indicated that structurally, both CMPS-II and CBPS-II were 1,3-branched-galactomannoglucan that had a linear backbone of (1→4)-linked α-d-glucopyranose (Glcp). Congo-red test revealed that CMPS-II and CBPS-II existed as triple-helical chains in 0.05–0.15M NaOH solution.
Systemic administration of oxaliplatin has no effect on the tumors in the central nervous system (CNS) due to the limited concentration of oxaliplatin in the cerebrospinal fluid (CSF), while it was ...clinically reported that oxaliplatin can induce acute encephalopathy. Currently, the impairment of neuronal functions in the CNS after systemic administration of oxaliplatin remains uninvestigated.
The von Frey test and the plantar test were performed to evaluate neuropathic pain behavior after a single intraperitoneal administration of oxaliplatin (4 mg/kg) in rats. Inductively coupled plasma-mass spectrometry, electrophysiologic recording, real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, Western blot, immunohistochemistry, and small interfering RNA were applied to understand the mechanisms.
Concentration of oxaliplatin in CSF showed a time-dependent increase after a single administration of oxaliplatin. Spinal application of oxaliplatin at the detected concentration (6.6 nM) significantly increased the field potentials in the dorsal horn, induced acute mechanical allodynia (n = 12 each) and thermal hyperalgesia (n = 12 each), and enhanced the evoked excitatory postsynaptic currents and spontaneous excitatory postsynaptic currents in the projection neurokinin 1 receptor-expressing lamina I to II neurons. The authors further found that oxaliplatin significantly increased the nuclear factor-κB p65 binding and histone H4 acetylation in cx3cl1 promoter region. Thus, the upregulated spinal CX3CL1 markedly mediated the induction of central sensitization and acute pain behavior after oxaliplatin administration.
The findings of this study suggested that oxaliplatin in CSF may directly impair the normal function of central neurons and contribute to the rapid development of CNS-related side effects during chemotherapy. This provides novel targets to prevent oxaliplatin-induced acute painful neuropathy and encephalopathy.
This study presents a new strategy to discriminate between opium samples obtained from different geographical regions. Nuclear magnetic resonance (NMR) profiling and chemometrics were applied to ...geographical classification of opium originating from Myanmar and Afghanistan, which are two major opium producing countries in the world. A total of 50 Myanmar and 46 Afghanistan authentic opium samples were analyzed by 1H‐NMR, and the chemical profiles were characterized. Different sample preparation procedures, data processing methods, and chemometrics were compared to obtain the best classification effect. It was found that drying and the addition of buffer solutions were unnecessary for classification purposes; thus, the gum opium samples were extracted directly with CD3OD, which shortened sample preparation time. A full discrimination between the two geographical origins was achieved by 1H‐NMR profiling and orthogonal partial least squares discriminant analysis. All 30 opium samples were classified correctly by the developed orthogonal partial least squares discriminant analysis model. Compared with traditional chromatography and mass spectrometry profiling methods, the 1H‐NMR profiling method was faster (with instrument analysis time of less than 3 min) and reproducible. This study provides new insights into the applying of NMR profiling and chemometrics to rapid drug profiling analysis.
NMR and OPLS‐DA were first used for the geographical classification of opium. Ninety‐five Myanmar and Afghanistan authentic opium were analyzed and characterized. The developed NMR method is fast with instrument analysis time of less than 3 min.
Cyclophilins, a type of peptidyl-prolyl cis-trans isomerase, function as important molecular chaperones in a series of biological processes. However, the expression pattern and signal transduction ...pathway of cyclophilins are still unclear. Here, we showed that the promoter of OsCYP2 could function as a tissue-specific promoter by GUS staining. Moreover, we found that the promoter sequence contained not only core elements but also inducible elements. Then, the ABA-responsive element was used for cDNA library screening, and the transcription factor MYC2-like was identified by a yeast one-hybrid assay and confirmed through an electrophoretic mobility shift assay. Furthermore, the relative expression showed that MYC2-like was induced by abscisic acid. In addition, MYC2-like overexpression enhanced salt tolerance in transformants and partially restored the cyp2-RNAi line. In summary, we explored a novel transcriptional signal mediated by MYC2-like, a potential regulator of salt stress-related physiological processes in rice.
Adult neurogenesis in hippocampus dentate gyrus (DG) is associated with the etiology on the early stage of Alzheimer's disease (AD). Factors that affect adult hippocampal neurogenesis have been shown ...to contribute to the neuropathology of AD. Adiponectin, a peptide hormone secreted by adipocytes, plays a critical role in insulin sensitizing, anti-inflammatory, and anti-diabetic effects in peripheral tissues. We previously showed that AdipoRon, as an agonist of adiponectin, promotes neurite outgrowth under ischemia. However, the role of AdipoRon on neural stem cells (NSCs) proliferation and cognitive dysfunction in the early stage of AD remains unknown. In this study, we investigated the role of AdipoRon on cognitive dysfunction and deficits of NSCs proliferation in AD. The in vivo study showed that AdipoRon improved either cognitive dysfunction or impaired NSCs proliferation in hippocampus DG region in APP/PS1 transgenic (Tg) mice. In addition, AdipoRon treatment also suppressed the β-amyloid (Aβ) deposition and inhibited β-secretase 1(BACE1) expression in both cortex and hippocampus of APP/PS1 Tg mice. The in vitro study further suggested that AdipoRon significantly alleviated Aβ-induced cell viability and neuronal morphology in primary neurons. Both AdipoR1 silencing and compound C, inhibitor of AMPK, completely abolished the effect of AdipoRon. Interestingly, AdipoRon also protected the dissipation of the ΔΨm caused by Aβ toxicity in primary neurons, which was reversed by compound C. In NE-4C NSCs, AdipoRon significantly promoted the Aβ-induced impaired cell proliferation through AdipoR1/AMPK/CREB pathway. Furthermore, inhibition of AMPK by compound C also reversed the promotive effects of AdipoRon on cognition and proliferation of NSCs of APP/PS1 Tg mice, suggesting a AMPK-dependent mechanism by AdipoRon in AD in vivo. Taken together, these results suggested that AdipoRon alleviated the cognitive dysfunction of AD mice, inhibited the Aβ deposition by inhibiting BACE1 expression and promoted the impaired hippocampal NSCs proliferation on the early stage in vivo. The mechanisms involved activation of AdipoR1/AMPK pathway. Therefore, AdipoRon might be a potential candidate for the treatment of AD on the early stage.
•AdipoRon ameliorates cognitive deficit of APP/PS1 mice.•AdipoRon alleviates Aβ-induced impairment of neuronal survival and NSC proliferation.•AdipoRon promotes NSC proliferation through activating AMPK pathway.
Clinically, neuropathic pain is a severe side effect of oxaliplatin chemotherapy, which usually leads to dose reduction or cessation of treatment. Due to the unawareness of detailed mechanisms of ...oxaliplatin-induced neuropathic pain, it is difficult to develop an effective therapy and limits its clinical use.
The aim of the present study was to identify the role of sirtuin 1 (SIRT1) reduction in epigenetic regulation of the expression of voltage-gated sodium channels 1.7 (Nav1.7) in the dorsal root ganglion (DRG) during oxaliplatin-induced neuropathic pain.
Controlled animal study.
University laboratory.
The von Frey test was performed to evaluate pain behavior in rats. Real-time quantitative polymerase chain reaction, western blotting, electrophysiological recording, chromatin immunoprecipitation, and small interfering RNA (siRNA) were used to illustrate the mechanisms.
In the present study, we found that both the activity and expression of SIRT1 were significantly decreased in rat DRG following oxaliplatin treatment. The activator of SIRT1, resveratrol, not only increased the activity and expression of SIRT1, but also attenuated the mechanical allodynia following oxaliplatin treatment. In addition, local knockdown of SIRT1 by intrathecal injection of SIRT1 siRNA caused mechanical allodynia in naive rats. Besides, oxaliplatin treatment enhanced the action potential firing frequency of DRG neurons and the expression of Nav1.7 in DRG and activation of SIRT1 by resveratrol reversed this effect. Furthermore, blocking Nav1.7 by ProTx II (a selective Nav1.7 channel blocker) reversed oxaliplatin-induced mechanical allodynia. In addition, histone H3 hyperacetylation at the Nav1.7 promoter in DRG of rats following oxaliplatin treatment was significantly suppressed by activation of SIRT1 with resveratrol. Moreover, both the expression of Nav1.7 and histone H3 acetylation at the Nav1.7 promoter were upregulated in the DRG by local knockdown of SIRT1 with SIRT1 siRNA in naive rats.
More underlying mechanism(s) of SIRT1 reduction after oxaliplatin treatment needs to be explored in future research.
These findings suggest that reduction of SIRT1-mediated epigenetic upregulation of Nav1.7 in the DRG contributes to the development of oxaliplatin-induced neuropathic pain in rats. The intrathecal drug delivery treatment of activating SIRT1 might be a novel therapeutic option for oxaliplatin-induced neuropathic pain.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key ...hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied.
•Compared with other subtypes of breast cancer, triple-negative breast cancer has obvious hypoxia characteristics and rich expression of HIF-1α.•In triple-negative breast cancer, HIF-1α is regulated by the NF-κB, RAS-RAF-MEK-ERK, PI3K/Akt/mTOR, and JAK-STAT signaling pathways.•HIF-1α is regulated by the level of oxygen contained in the tumor.•In triple negative breast cancer, HIF-1α can be targeted by reducing the expression level of HIF-1α, promoting HIF-1α protein degradation, inhibiting HIF-1α protein synthesis and inhibiting HIF-1α dimerization.
The influence of interfaces represents a critical factor affecting the use of solid-state batteries (SSBs) in a wide range of practical industrial applications. However, our current understanding of ...this key issue remains somewhat limited. Therefore, this review presents the mechanisms and advanced characterization techniques associated with interfaces in SSBs. First, we compare liquid- and solid-state batteries and emphasize the challenges in solid-solid interfaces. Second, we discuss different aspects of interfaces including interphase formation, cathode-electrolyte interface, anode-electrolyte interface, and interparticle interface, which contain a detailed description of the formation mechanisms and current research. Third, the characterization strategies for effective interfacial observation and analysis are summarized and discussed. In particular, two unique characterization techniques, vibrational sum-frequency generation spectroscopy and on-chip single-nanowire battery characterization, are highlighted. Lastly, we summarize the scientific issues associated with solid-solid interfaces and provide our perspectives to better understand the fundamental issues and improve the performance of SSBs.
Display omitted
Lithium-ion batteries (LIBs) are the promising power sources for portable electronics, electric vehicles, and smart grids. The recent LIBs with organic liquid electrolytes still suffer from safety issues and insufficient lifetime. Solid-state batteries (SSBs) are expected to address these issues. In principle, the nonflammable solid electrolytes could prevent battery combustion and explosion, and only Li ions are mobile in solid electrolytes, which could suppress side reactions. Some solid electrolytes, such as sulfides, have sufficiently high ionic conductivity, which is comparable to that of with organic liquid electrolytes. Thus, solid-solid interfaces appear to be the key to push SSBs toward practical applications. In this review, we start by introducing the challenges in solid-solid interfaces versus liquid-solid interfaces. We then discuss different interfaces in SSBs, including cathode-electrolyte interface, anode-electrolyte interface, and interparticle interface. Lastly, we present the advanced characterization techniques to help deepen understanding of the composition and structure evolution at the interfaces during battery cycling. The on-chip single-nanowire electrochemical devices developed by our group are highlighted as a unique platform for in situ characterization.
We suggest and emphasize some future directions for SSBs. First, different in situ or operando characterization techniques should be developed and combined to track the real-time composition and structure changes at the interfaces in SSBs. Second, in addition to metal ions, metal-air and metal-sulfur systems with much higher energy density should also receive sufficient attention for SSBs. Lastly, a unique advantage of SSBs over liquid-electrolyte batteries is that SSBs could be flexible, stretchable, and shrunk on a chip. Thus, SSBs are promising for integration with microelectronic circuits to fabricate self-powered wearable or implantable micro-/nanoscale devices.
SSB with a nonflammable solid electrolyte is a promising approach to address the safety issues of rechargeable batteries with flammable liquid organic electrolyte. However, the high impedance and/or instability of the solid-solid interfaces limit the practical applications of SSBs. This review focuses on the mechanisms and advanced characterization techniques associated with interfaces in SSBs, as well as provides our perspectives on future directions to better understand the fundamental issues and improve the performance of SSBs.
Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA ...(mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18 deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results reveal a crucial role for circRNA in regulating mitochondrial dynamics and apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic avenue for cardiovascular diseases.
Gut microbiota** play important roles in the health and disease status of both humans and animals. Little is known about whether heat stress changes the composition of the gut microbiota in chicken. ...The aim of this study was to investigate the effects of heat stress on changes in caecal microbiota, including changes in growth performance as well as HSP70 and cortisol levels. Sixty 14-day-old female broilers were equally divided into 2 treatment groups with different housing temperatures for 28 D: a control group (C) at 24 to 26°C and a heat stress (HS) group at 34 to 38°C. The caecal contents of the broiler chicken were then extracted on days 1, 3, 7, 14, and 28. Genomic DNA was extracted and amplified based on the V3∼V4 hypervariable region of 16S rRNA high-throughput sequence analyses. The results showed that the average daily gain and average daily feed intake were significantly decreased and that the feed conversion ratio was increased by heat stress. The concentrations of HSP70 and cortisol in the serum were significantly increased. The composition of gut microbiota was influenced by heat stress** through beta diversity analysis and taxon-based analysis. In particular, at the phylum level the composition of Firmicutes, Tenericutes, and Proteobacteria in HS group was increased than that of C group, and Bacteroidetes and Cyanobacteria in HS group were reduced than that of C group. In addition, the composition of Anaeroplasma and Lactobacillus phyla in HS group were increased than that of C group, whereas the Bacteroides, Oscillospira, Faecalibacterium, and Dorea genera in HS group were decreased than that of C group. In conclusion, the gut microbiota in broilers were changed by heat stress. And the changes of the gut microbiota could provide the basis for further research on the heat stress.
PDF
