Comparative transcriptome revealed the molecular responses of Aconitum carmichaelii Debx. to downy mildew at different stages of disease development.

BACKGROUND: Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages. RESULTS: The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses. CONCLUSIONS: In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew.

Effects of frying on the surface oil absorption of wheat, potato, and pea starches.

The effects of structural changes on surface oil absorption characteristics of wheat starch, pea starch and potato starch during frying under different water content (20%, 30%, 40%, 50%) were studied. Fried potato starch with a 40% water content exhibited the highest surface oil content. When the initial moisture content reached 30%, the scattering intensity of the crystal layer structure decreased for wheat and pea starches, while the scattering peak for potato starch completely disappeared. At 40% moisture content, the amorphous phase ratio values for fried potato, wheat and pea starches were 13.50%, 11.78% and 11.24%, respectively, and the nitrogen adsorption capacity of fried starch decreased in turn. These findings that the structure of potato starch was more susceptible to degradation compared to pea starch and wheat starch, resulting in higher surface oil absorbed by potato starch during frying process.

Peroxydisulfate activation and versatility of defective Fe3O4@MOF-808 for enhanced carbon and phosphorus recovery from sludge anaerobic fermentation.

Although being viewed as a promising technology for reclamation of carbon and phosphorus from excess sludge, anaerobic fermentation (AF) grapples with issues such as a low yield of volatile fatty acids (VFAs) and high phosphorus recovery costs. In this study, we synthesized Fe3O4@MOF-808 (FeM) with abundant defects and employed it to simultaneously enhance VFAs and phosphorus recovery during sludge anaerobic fermentation. Through pre-oxidization of sludge catalyzed by FeM-induced peroxydisulfate, the soluble organic matter increased by 2.54 times, thus providing ample substrate for VFAs production. Subsequent AF revealed a remarkable 732.73 % increase in VFAs and a 1592.95 % increase in phosphate. Factors contributing to the high VFAs yield include the non-biological catalysis of unsaturated Zr active sites in defective FeM, enhancing protein hydrolysis, and the inhibition of methanogenesis due to electron competition arising from the transformation between Fe(III) and Fe(II) under Zr influence. Remarkably, FeM exhibited an adsorption capacity of up to 92.64 % for dissolved phosphate through ligand exchange and electrostatic attractions. Furthermore, FeM demonstrated magnetic separation capability from the fermentation broth, coupled with excellent stability and reusability in both catalysis and adsorption processes.

Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups.

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.

Dendrobium officinale Polysaccharides as a Natural Functional Component for Acetic-Acid-Induced Gastric Ulcers in Rats.

Dendrobium officinale is an important edible and medicinal plant, with the Dendrobium officinale polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this study, DOP was extracted and characterized for its structural properties. The potential of DOP to ameliorate gastric ulcers (GUs) was investigated using an acetic-acid-induced GU model in rats. The results demonstrated that DOP exerted a multifaceted protective effect against GU, mitigating the deleterious impact on food intake and body weight in rats. DOP exhibited its protective action by attenuating cellular damage attributed to oxidative stress and inflammatory reactions mediated by enhanced activities of SOD, GSH, and GSH-PX, coupled with a downregulation in the expression of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Furthermore, DOP effectively inhibited apoptosis in gastric mucosa cells of acetic-acid-induced GU rat models and facilitated the self-repair of damaged tissues. Remarkably, the DOP-200 and DOP-400 groups outperformed omeprazole in reducing the expression of IL-6 and malondialdehyde (MDA) in tissues, as well as IL-1ß, IL-6, and TNF-α in serum. These groups also exhibited an improved expression of SOD in tissues and SOD, GSH, and GSH-PX in serum. A Western blot analysis of gastric mucosa demonstrated that the DOP-200 and DOP-400 groups significantly reduced the expression of NF-κBp65, phosphorylated NF-κBp65, FoxO3a, and Bim. The observed antagonism to GU appeared to be associated with the NF-κB cell pathway. Additionally, qRT-PCR results indicate that DOP reduced the mRNA transcription levels of IL-6, and TNF-α, which shows that the healing of GU is related to the reduction in the inflammatory reaction by DOP. However, the expression of EGF and VEGF decreased, suggesting that the mechanism of DOP inhibiting GU may not be directly related to EGF and VEGF, or there is an uncertain competitive relationship between them, so further research is needed.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner.

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.

Alzheimer's disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aß proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD's pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aß1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aß-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aß toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.

[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring.

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

Study of the Correlation between the Motor Ability of the Individual Upper Limbs and Motor Imagery Induced Neural Activities.

Motor imagery based brain-computer interfaces (MI-BCIs) have excellent application prospects in motor enhancement and rehabilitation. However, MI-induced electroencephalogram features applied to MI-BCI usually vary from person to person. This study aimed to investigate whether the motor ability of the individual upper limbs was associated with these features, which helps understand the causes of inter-subject variability. We focused on the behavioral and psychological factors reflecting motor abilities. We first obtained the behavioral scale scores from Edinburgh Handedness Questionnaire, Maximum Grip Strength Test, and Purdue Pegboard Test assessments to evaluate the motor execution ability. We also required the subjects to complete the psychological Movement Imagery Questionnaire-3 estimate, representing MI ability. Then we recorded EEG signals from all twenty-two subjects during MI tasks. Pearson correlation coefficient and stepwise regression were used to analyze the relationships between MI-induced relative event-related desynchronization (rERD) patterns and motor abilities. Both Purdue Pegboard Test and Movement Imagery Questionnaire-3 scores had significant correlations with MI-induced neural oscillation patterns. Notably, the Purdue Pegboard Test of the left hand had the most significant correlation with the alpha rERD. The results of stepwise multiple regression analysis showed that the Purdue Pegboard Test and Movement Imagery Questionnaire-3 could best predict the MI-induced rERD. The results demonstrate that hand dexterity and fine motor coordination are significantly related to MI-induced neural activities. In addition, the method of imagining is also relevant to MI features. Therefore, this study is meaningful for understanding individual differences and the design of user-centered MI-BCI.

Multidimensional Drivers of Mercury Distribution in Global Surface Soils: Insights from a Global Standardized Field Survey.

Soil stores a large amount of mercury (Hg) that has adverse effects on human health and ecosystem safety. Significant uncertainties still exist in revealing environmental drivers of soil Hg accumulation and predicting global Hg distribution owing to the lack of field data from global standardized analyses. Here, we conducted a global standardized field survey and explored a holistic understanding of the multidimensional environmental drivers of Hg accumulation in global surface soils. Hg content in surface soils from our survey ranges from 3.8 to 618.2 µg kg-1 with an average of 74.0 µg kg-1 across the globe. Atmospheric Hg deposition, particularly vegetation-induced elemental Hg0 deposition, is the major source of surface soil Hg. Soil organic carbon serves as the major substrate for sequestering Hg in surface soils and is significantly influenced by agricultural management, litterfall, and elevation. For human activities, changing land-use could be a more important contributor than direct anthropogenic emissions. Our prediction of a new global Hg distribution highlights the hot spots (high Hg content) in East Asia, the Northern Hemispheric temperate/boreal regions, and tropical areas, while the cold spots (low Hg content) are in arid regions. The holistic understanding of multidimensional environmental drivers helps to predict the Hg distribution in global surface soils under a changing global environment.

Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study.

BACKGROUND: Coffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents. METHODS: Based on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs). RESULTS: In epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (ß = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (ß = 0.0019, P = 0.7552), and total spine BMD (ß = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (ß = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (ß = 0.0202, P = 0.7828). CONCLUSIONS: Our study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS.

ABSTRACT: T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased. Supplementation with nicotinamide ribose (NR), the precursor of NAD + , right after cecal ligation and puncture significantly increased the levels of NAD + and SIRT1. Supplementation with NR alleviated the depletion of mononuclear cells and T lymphocytes in spleen in sepsis and increased the levels of CD3 + CD4 + and CD3 + CD8 + T cells. Interestingly, both Th1 and Th2 cells were expanded after NR treatment, but the balance of Th1/Th2 was partly restored. Nicotinamide ribose also inhibited the regulatory T cells expansion and programmed cell death 1 expression in CD4 + T cells in sepsis. In addition, the bacteria load, organ damage (lung, heart, liver, and kidney), and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD + /SIRT1 pathway.

Incorporating EEG and fNIRS Patterns to Evaluate Cortical Excitability and MI-BCI Performance During Motor Training.

As electroencephalography (EEG) is nonlinear and nonstationary in nature, an imperative challenge for brain-computer interfaces (BCIs) is to construct a robust classifier that can survive for a long time and monitor the brain state stably. To this end, this research aims to improve BCI performance by incorporation of electroencephalographic and cerebral hemodynamic patterns. A motor imagery (MI)-BCI based visual-haptic neurofeedback training (NFT) experiment was designed with sixteen participants. EEG and functional near infrared spectroscopy (fNIRS) signals were simultaneously recorded before and after this transient NFT. Cortical activation was significantly improved after repeated and continuous NFT through time-frequency and topological analysis. A classifier calibration strategy, weighted EEG-fNIRS patterns (WENP), was proposed, in which elementary classifiers were constructed by using both the EEG and fNIRS information and then integrated into a strong classifier with their independent accuracy-based weight assessment. The results revealed that the classifier constructed on integrating EEG and fNIRS patterns was significantly superior to that only with independent information (  âˆ¼  10% and  âˆ¼  18% improvement respectively), reaching  âˆ¼  89% in mean classification accuracy. The WENP is a classifier calibration strategy that can effectively improve the performance of the MI-BCI and could also be used to other BCI paradigms. These findings validate that our proposed methods are feasible and promising for optimizing conventional motor training methods and clinical rehabilitation.

BSHXF-medicated serum combined with ADSCs regulates the TGF-ß1/Smad pathway to repair oxidatively damaged NPCs and its component analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-ß1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-ß-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1ß, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-ß1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-ß1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-ß1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1ß and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-ß1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.

Folic acid relieves bone cancer pain by downregulating P2X2/3 receptors in rats.

BACKGROUND: Bone cancer pain (BCP) remains a clinical challenge due to the limited and side effects of therapeutic methods. Folic acid has been known as an FDA approved dietary supplement and proved to have an analgesic effect in neuropathic pain. Here we investigate the role and mechanism of folic acid in bone cancer pain of a rat model. METHODS: Walker 256 tumor cells were inoculated into the left tibia of rats to induce bone cancer pain model. Pain reflex were assessed by paw withdrawal threshold (PWT) response to Von Frey filaments and paw withdrawal latency (PWL) response to thermal stimulation. Folic acid was injected intraperitoneally to evaluate its analgesic effect in rats with bone cancer pain. Western blotting and qPCR were used to determine P2X2/3 receptor protein and mRNA levels in ipsilateral L4-6 dorsal root ganglion (DRG) and spinal dorsal horn (SDH). RESULTS: The PWT and PWL of rats with bone cancer pain were obviously decreased compared to the naïve and sham rats. Interestingly, continuous folic acid treatment significantly increased the PWT and PWL of rats with bone cancer pain. P2X2 and P2X3 receptors were clearly upregulated at both mRNA and protein expression in L4-6 DRG and SDH of rats with bone cancer pain. P2X2 and P2X3 receptors were mainly localized with CGRP (calcitonin gene-related peptide) or IB4 (isolectin B4) positive neurons in L4-6 DRG of rats with bone cancer pain. Notably, continuous folic acid treatment significantly reduced the expression of P2X2 and P2X3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Finally, intrathecal injection of A317491 (a selective antagonist of P2X2/3 receptors) markedly elevated the PWT and PWL of rats with bone cancer pain. CONCLUSION: These results suggest that folic acid has an effective antinociceptive effect on bone cancer pain, which is mediated by downregulating P2X2/3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Folic acid may be a novel therapeutic strategy in cancer patients for pain relief.

Motor Imagery and Action Observation Induced Electroencephalographic Activations to Guide Subject-Specific Training Paradigm: A Pilot Study.

Brain-computer interface (BCI)-based motor rehabilitation feedback training system can facilitate motor function reconstruction, but its rehabilitation mechanism with suitable training protocol is unclear, which affects the application effect. To this end, we probed the electroencephalographic (EEG) activations induced by motor imagery (MI) and action observation (AO) to provide an effective method to optimize motor feedback training. We grouped subjects according to their alpha-band sensorimotor cortical excitability under MI and AO conditions, and investigated the EEG response under the same paradigm between groups and different motor paradigms within group, respectively. The results showed that there were significant differences in sensorimotor activations between two groups of subjects. Specifically, the group with weaker MI induced EEG features, could achieve stronger sensorimotor activations in AO than that of other conditions. The group with stronger MI induced EEG features, could achieve stronger sensorimotor activations in the MI+AO than that of other conditions. We also explored their classification and brain network differences, which might try to explain the EEG mechanism in different individuals and help stroke patients to choose appropriate subject-specific motor training paradigm for their rehabilitation and better treatment outcomes.

Preparation of robust, water-resistant, antibacterial, and antioxidant chitosan-based films by incorporation of cinnamaldehyde-tannin acid-zinc acetate nanoparticles.

Chitosan (CS) films have poor mechanical property, low water-resistance and limited antimicrobial activity, which hinder their application in food preservation industry. Cinnamaldehyde-tannic acid-zinc acetate nanoparticles (CTZA NPs) assembled from edible medicinal plant extracts were successfully incorporated into CS films to solve these issues. The tensile strength and water contact angle of the composite films increased about 5.25-fold and 17.55°. The addition of CTZA NPs reduced the water sensitivity of CS films, which could undergo appreciable stretching in water without breaking. Furthermore, CTZA NPs significantly enhanced the UV adsorption, antibacterial, and antioxidant properties of the films, while reduced their water vapor permeability. Moreover, it was possible to print inks onto the films because the presence of the hydrophobic CTZA NPs facilitated the deposition of carbon powder onto their surfaces. The films with great antibacterial and antioxidant activities can be applied for food packaging application.