Study on material basis and anti-hypertensive metabolomics of Zhengan-Xifeng-Tang(ZXT): A comparison between ZXT decoction and granules.

High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients.

A Dual-Function Hemicyanine Material with Highly Efficient Photothermal and Photodynamic Effect Used for Tumor Therapy.

Small molecular organic optical agents with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), hold credible promise for anti-tumor therapy by overcoming individual drawbacks and enhancing photon utilization efficiency. However, developing effective dual-function PTT-PDT photosensitizers (PSs) for efficient synergistic phototherapy remains challenging. Here, a benz[c,d]indolium-substituted hemicyanine named Rh-BI, which possesses a high photothermal conversion efficiency of 41.67% by exhaustively suppressing fluorescence emission, is presented. Meanwhile, the rotating phenyl group at meso-site induces charge recombination to enhance the molar extinction coefficient up to 13.58 × 104 M-1cm-1, thereby potentiating the photodynamic effect. Under 808 nm irradiation, Rh-BI exhibits significant phototoxicity in several cancer cell types in vitro with IC50 values as low as ≈0.5 µM. Moreover, treatment of 4T1 tumor-bearing mice with Rh-BI under laser irradiation successfully inhibits tumor growth. In a word, an effective strategy is developed to build PTT-PDT dual-functional optical materials based on hemicyanine backbone for tumor therapy by modulating conjugation system interaction to adjust the energy consumption pathway.

Tu-Xian Decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1.

Tu-Xian decoction (TXD), a traditional Chinese medicine (TCM) formula, has been frequently administered to manage diabetic cognitive impairment (DCI). Despite its widespread use, the mechanisms underlying TXD's protective effects on DCI have yet to be fully elucidated. As a significant regulator in neurodegenerative conditions, death-associated protein kinase-1 (DAPK-1) serves as a focus for understanding the action of TXD. This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1. To this end, a diabetic model was established using Sprague-Dawley (SD) rats through a high-fat, high-sugar (HFHS) diet regimen, followed by streptozotocin (STZ) injection. The experimental cohort was stratified into six groups: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD groups. Following a 12-week treatment period, various assessments-including blood glucose levels, body weight measurements, Morris water maze (MWM) testing for cognitive function, brain magnetic resonance imaging (MRI), and histological analyses using hematoxylin-eosin (H&E), and Nissl staining-were conducted. Protein expression in the hippocampus was quantified through Western blotting analysis. The results revealed that TXD significantly improved spatial learning and memory abilities, and preserved hippocampal structure in diabetic rats. Importantly, TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region. These results underscore TXD's potential in mitigating DCIvia DAPK-1 inhibition, positioning it as a viable therapeutic candidate for addressing this condition. Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.

Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat.

Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension.

CenhANCER: a comprehensive cancer enhancer database for primary tissues and cell lines.

Enhancers, which are key tumorigenic factors with wide applications for subtyping, diagnosis and treatment of cancer, are attracting increasing attention in the cancer research. However, systematic analysis of cancer enhancers poses a challenge due to the lack of integrative data resources, especially those from tumor primary tissues. To provide a comprehensive enhancer profile across cancer types, we developed a cancer enhancer database CenhANCER by curating public resources including all the public H3K27ac ChIP-Seq data from 805 primary tissue samples and 671 cell line samples across 41 cancer types. In total, 57 029 408 typical enhancers, 978 411 super-enhancers and 226 726 enriched transcription factors were identified. We annotated the super-enhancers with chromatin accessibility regions, cancer expression quantitative trait loci (eQTLs), genotype-tissue expression eQTLs and genome-wide association study risk single nucleotide polymorphisms (SNPs) for further functional analysis. The identified enhancers were highly consistent with accessible chromatin regions in the corresponding cancer types, and all the 10 super-enhancer regions identified from one colorectal cancer study were recapitulated in our CenhANCER, both of which testified the high quality of our data. CenhANCER with high-quality cancer enhancer candidates and transcription factors that are potential therapeutic targets across multiple cancer types provides a credible resource for single cancer analysis and for comparative studies of various cancer types. Database URL http://cenhancer.chenzxlab.cn/.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.

Reservoir flood regulation affects nutrient transport through altering water and sediment conditions.

The effect of reservoir construction on nutrient dynamics is well recognized, at flood event-scale influence of reservoir flood regulation on nutrient transport however has received less attention. Taking the Three Gorges Reservoir (TGR) in the Changjiang River as an example, during the TGR's regulation on a flood in Sep., 2021, this study collected water samples along the mainstream of the reservoir as well as pre/post-dam, with the aim to identify the impact of flood regulation on nutrient (nitrogen and phosphorus) distribution and transportation. Results show that nitrate nitrogen (NO3N) and particulate phosphorus (PP) were the main fraction of the total nitrogen (TN) and total phosphorus (TP) with the proportion of 46.5%-95.6% and 57.4%-81.6%, respectively. N and P responded different to flood regulation: (i) along the stream P concentration significantly decreased due to PP deposited with sediment while N concentration barely changed during flood regulation; (ii) P concentration was significantly higher at post-dam section than at pre-dam section, while N concentration maintained the same. The diffed response to flood regulation caused TN/TP ratio increased from 4 to 8 in the reservoir tail to over 20 near the dam, which probably arise eutrophication in the reservoir head area. This study reveals the influence of flood regulation on nutrient transport in flood event and provides scientific basis for reservoir management.

Mucoadhesive Nanoparticles Enhance the Therapeutic Effect of Dexamethasone on Experimental Ulcerative Colitis by the Local Administration as an Enema.

Background: As the first-line drug to treat ulcerative colitis (UC), long-term use of glucocorticoids (GCs) produces severe toxic and side effects. Local administration as enema can increase the local GCs concentrations and reduce systemic exposure to high oral doses by directly delivering GCs to the inflammation site in the distal colorectum. However, UC patients are often accompanied by diarrhea, leading to the short colonic residence time of GCs and failure to exert their function fully. Purpose: A kind of mucoadhesive nanoparticles (NPs) loading different dexamethasone derivatives (DDs) were developed, which could attach to the positively charged inflammatory colonic mucosa through electrostatic adsorption after administered by enema, thereby improving the local concentration and achieving effective targeted therapy for UC. Methods: Two DDs, dexamethasone hemisuccinate and dexamethasone phosphate, were synthesized. In NPs preparation, The core PEI-DDs NPs were built by the electrostatic adsorption of DDs and the cationic polymer polyethyleneimine (PEI). Then, the natural polyanionic polysaccharide sodium alginate (SA) was electronically coated around NPs to construct the final SA-PEI-DDs NPs, followed by the in vitro stability and release tests, in vitro and in vivo colonic mucosal adhesion tests. In the in vivo anti-UC test, the experimental colitis mice were induced by 2,4,6-trinitrobenzenesulfonic acid. The body weight and disease activity index changes were measured, and the myeloperoxidase activity, pro-inflammatory cytokines concentration, and hematoxylin and eosin staining were also investigated to evaluate the therapeutic effect of NPs. Results: The structures of two DDs were demonstrated by 1H-NMR and MS. Both NPs were negatively charged and achieved high loading efficiency of DDs, while their particle sizes were significantly different. NPs showed good stability and sustained release properties in the simulated colonic environment. Moreover, the negative charge on the of NPs surface made them easier to adhere to the positively charged inflammatory colonic mucosa, thereby enhancing the enrichment and retention of DDS in the colitis site. Furthermore, the NPs exhibited better therapeutic effects than free Dex on the experimental colitis mice induced by TNBS through the enema rectal. Conclusion: These results indicated the mucoadhesive NPs as a kind of novel nano-enema showed great potential to achieve efficient treatment on UC.

Isorhynchophylline Regulates the Circadian Rhythm of the Hypothalamus in Spontaneously Hypertensive Rats to Treat Hypertension.

BACKGROUND: The neurotransmitter metabolism in spontaneously hypertensive rats (SHR) is disordered, and these disturbances in neurotransmitter levels can further exacerbate the development of hypertension. Neurotransmitters can affect the expression of circadian clock genes. OBJECTIVE: To clarify the time-dependent internal mechanism of the imbalance of the target neurotransmitter metabolic rhythm of spontaneously hypertensive rats, the circadian research was carried out by the method of targeted metabolomics and molecular biology technology. METHODS: We have explored the mechanism of isorhynchophylline regulating the circadian rhythm through the ERK signaling pathway and thus treating hypertension by detecting the changes of central hypothalamic biological clock rhythm genes after isorhynchophylline intervention, from hypothalamic neurotransmitter rhythmicity. RESULTS: The expression of rhythm genes in normal rats showed a certain rhythm at 6 time points, while the expression of rhythm genes in model rats decreased, and the gene rhythm returned to normal after isorhynchophylline treatment. Cosine analysis of 12 neurotransmitters in hypothalamus showed that there were 6 rhythmic neurotransmitters in the normal group, while in the model group, 4 of the 6 neurotransmitters lost their rhythmicity, and the rhythmicity returned to normal after isorhynchophylline intervention. Compared with the normal group, the expression of ERK protein in the model group increased significantly and decreased after isorhynchophylline treatment. CONCLUSION: The mechanism of isorhynchophylline treating hypertension is not only the regulation of serum neurotransmitters rhythm, but also acting on rhythm genes in the feedback loop of the central biological clock.

Electrokinetic geosynthetics restrained nitrogen release from sediment to overlying water through porewater drainage.

Porewater is the primary carrier of sediment nitrogen and a crucial source of overlying water nitrogen; its separation thus is essential for restraining nitrogen release from sediment to overlying water. We developed a novel device using electrokinetic geosynthetics to drain porewater with nitrogen and restrain nitrogen release. A batch experiment lasted 1120 h (about 47 days) was conducted with 20 cm depth of overlying water under three conditions, i.e., undrained at 0 V/cm voltage gradient (control), drained at 0 V/cm, and drained at 0.5 V/cm. Under the pulsed direct current, once porewater drained, overlying water replenished sediment pore space and supplied porewater. Along with porewater drainage, sediment nitrogen concentration was reduced by 11%-30%, decreasing nitrogen release from sediment to overlying water from 83 mg/m2 in the first 100 h to -95 mg/m2 after about 600 h. Processes such as electroosmosis, electromigration, and redox reaction contributed to the restraint on nitrogen release. This research revealed the potentiality of applying electrokinetic geosynthetics to in-situ restraint on sediment nitrogen release in eutrophic waterbodies such as fishponds.

Hernandezine Regulates Proliferation and Autophagy-Induced Apoptosis in Melanoma Cells.

Hernandezine is isolated from an herbal medicine that selectively inhibits multidrug resistance and improves the efficacy of drugs for cancer treatment. To date, no studies on hernandezine in melanoma have been conducted. In this study, hernandezine was found to inhibit proliferation and induce apoptosis in melanoma A375 cells and B16 cells. In hernandezine-treated melanoma cells, G0/G1 cycle arrest occurred accompanied by significantly downregulated levels of phosphorylated JAK2 and STAT3. In addition, the cycle arrest could be enhanced by AG490 (JAK2 inhibitor), suggesting that the JAK2/STAT3 pathway is involved in cell cycle regulation in hernandezine-treated melanoma cells. Hernandezine-treated melanoma cells exhibited autophagy-specific structures, autophagy markers (LC3II/LC3-I), and autophagic flow over time. Moreover, 3-MA (autophagy inhibitor) significantly inhibited apoptosis, indicating that hernandezine promotes apoptosis by inducing autophagy. Combined with differential expression of P-AMPK, P-ACC (downstream targets of adenine monophosphate activated protein kinase, AMPK), and P-p70S6K (downstream targets of mammalian target of rapamycin, mTOR) and significant inhibition of apoptosis by AMPK inhibitor complex C (CC) in hernandezine-treated melanoma cells suggested that hernandezine could induce autophagy via the AMPK-mTOR pathway, thereby inducing apoptosis. This study first analyzed the effect of melanoma cells by hernandezine and provided a theory for hernandezine in the treatment of melanoma.

Effect of zero-valent iron and granular activated carbon on nutrient removal and community assembly of photogranules treating low-strength wastewater.

Traditional wastewater treatment processes with high energy consumption and greenhouse gas emissions are not suitable for rural areas with low sewage strength and wide distribution. In this study, a microalgae-bacteria synergistic photogranules system was developed under the impetus of green chemical additives to address these challenges. The results showed that zero-valent iron (ZVI) or granular activated carbon (GAC) addition made successful photogranulation treating low-strength wastewater with excellent settleability and stability performance (settling velocity: 14-22 m h-1; integrity coefficient: 0.81-6.62%), while systems without light or additives failed due to the bio-granules disintegration caused by the overgrowth of predators or phototrophic species. A better nutrient removal performance (TN < 15 mg L-1, TP < 0.4 mg L-1) was observed in photogranules systems, and stoichiometric and biological analysis found that the divisions of nitrogen removal by microalgae and bacteria were different for photogranules between GAC and ZVI additions. As a physical enhancer, GAC can be used as the nucleus of photogranules regenerating after granules disintegration rather than affecting the community succession process. However, ZVI addition strengthened the sedimentation ability and stability of photogranules through chemical and biological effects, focusing on enhancing bacterial community diversity, enriching biofilm formation bacteria and inhibiting the overgrowth of filamentous cyanobacteria. Notably, the photogranules process with ZVI addition could be operated under non-aeration conditions without compromising removal efficiency. There existed an ideal distribution of microalgae and bacterial functional species in the photogranules, which seemed to be essential for its self-sustained synergistic symbiosis and stability. Consequently, this work might provide engineering alternatives for realizing carbon neutrality and environmental sustainability of the decentralized wastewater treatment process for low-strength wastewater in rural areas.

Enhancing immune responses to inactivated foot-and-mouth virus vaccine by a polysaccharide adjuvant of aqueous extracts from Artemisia rupestris L.

BACKGROUND: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. OBJECTIVES: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. METHODS: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. RESULTS: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4⁺ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. CONCLUSIONS: These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.

The Adjuvant Effects on Vaccine and the Immunomodulatory Mechanisms of Polysaccharides From Traditional Chinese Medicine.

Vaccination is still the most successful strategy to prevent and control the spread of infectious diseases by generating an adequate protective immune response. However, vaccines composed of antigens alone can only stimulate weak immunogenicity to prevent infection in many cases. Adjuvant can enhance the immunogenicity of the antigens. Therefore, adjuvant is urgently needed to strengthen the immune response of the vaccines. An ideal adjuvant should be safe, cheap, biodegradable and biologically inert. In addition to having a long shelf life, it can also promote cellular and humoral immune responses. Traditional Chinese medicine (TCM) has many different ingredients, such as glycosides, polysaccharides, acids, terpenes, polyphenols, flavonoids, alkaloids, and so on. TCM polysaccharides are one of the main types of biologically active substances. They have a large range of pharmacological activities, especially immunomodulatory. TCM polysaccharides can regulate the immune system of animals by binding to multiple receptors on the surface of immune cells and activating different signal pathways. This review focuses on a comprehensive summary of the most recent developments in vaccine adjuvant effects of polysaccharides from many important TCM, such as Artemisia rupestris L., Cistanche deserticola, Pinus massoniana, Chuanminshen violaceum, Astragalus, Ganoderma lucidum, Codonopsis pilosula, Lycium barbarum, Angelica, Epimedium, and Achyranthes bidentata. Moreover, this review also introduces their immunomodulatory effects and the molecular mechanisms of action on animal bodies, which showed that TCM polysaccharides can activate macrophages, the signal pathway of T/B lymphocytes, regulate the signal pathway of natural killer cells, activate the complement system, and so on.

A new method for the treatment of kitchen waste: Converting it into agronomic sprayable mulch film.

This report describes a new method for converting kitchen waste (KW) with high water content into mulch films that can be applied in agricultural production. Specifically, the KW was emulsion polymerized with acrylic monomers (in various proportions) to obtain a series of sprayable bio-based KW-acrylate mulch films. The films' properties and performances were evaluated, and the experimental results showed that the KW-acrylate mulch films exhibited excellent sprayability, membrane formation, and mechanical properties, which allowed them to effectively reduce soil water evaporation (by 13-50%) and increase soil temperature (by 1.9-6.7%). Compared with bare soil, the soil treated with the optimized KW-acrylate mulch film increased the germination rate of rapeseeds by 20% and the yield of Chenopodium album by 0.7 times; the mulch film biodegradation then reached 70% after 100 days.

Immune-Enhancing Activity of Aqueous Extracts from Artemisia rupestris L. via MAPK and NF-kB Pathways of TLR4/TLR2 Downstream in Dendritic Cells.

Artemisia rupestris L. has long been used as a traditional herbal medicine owing to its immunomodulatory activity. Aqueous extracts of Artemisia rupestris L. (AEAR) contain the main functional component and can activate the maturation of dendritic cells (DCs) and enhance the adaptive immunity as the adjuvant against infections. To explore the underlying mechanism of immunomodulatory activities of AEAR, DCs were produced from bone-marrow cells of mice and the effects of AEAR on cell viability were assessed by the Cell Counting Kit 8 (CCK8) method and annexin V/propidium iodide staining assays. Then, the effects of AEAR on the morphology, maturation, and function of DCs were detected using a microscope, flow cytometry-based surface receptor characterization, and endocytosis assays. The secretion levels of cytokines were then analyzed with enzyme-linked immunosorbent assay (ELISA). The activation state of DCs was evaluated by the mixed lymphocyte reaction (MLR). The activity of MAPKs and NF-κB pathways, which were involved in the regulation of AEAR on DCs, was further detected by Western blot. AEAR did not have a cytotoxic effect on DCs or mouse splenocytes. AEAR remarkably enhanced the phenotypic maturation of DCs and promoted the expression of costimulatory molecules and the secretion of cytokines in DCs. AEAR also significantly decreased the phagocytic ability of DCs and augmented the abilities of DCs to present antigens and stimulate allogeneic T-cell proliferation. Simultaneously, AEAR potently activated toll-like receptor (TLR)4-/TLR2-related MAPKs and induced the degradation of IκB and the translocation of NF-κB. In short, AEAR can profoundly enhance the immune-modulating activities of DCs via TLR4-/TLR2-mediated activation of MAPKs and NF-κB signaling pathways and is a promising candidate immunopotentiator for vaccines.

Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peach kernel (taoren: TR) is the dried mature seed of peach, Prunus persica (L.) Batsch, which belongs to the Rosaceae family. Rhubarb (dahuang: DH) is the dried root and rhizome of rhubarb (Rheum palmatum L., Rheum officinale Baill., or Rheum tanguticum Maxim. ex Balf.). TR-DH (TD) is a traditional Chinese medicine herb pair that promotes blood circulation and removes blood stasis. In recent years, TD has shown definite benefits in the cardio-cerebrovascular system, but its specific mechanism is not very clear. AIM OF STUDY: The purpose of this study was to explore the mechanism by which TD affects cerebral ischaemia/reperfusion (I/R) injury and to optimize the mixture ratio. METHODS: The affected metabolic pathways in rat brain tissues after I/R were analysed by network pharmacology and verified with animal pharmacological experiments. RESULTS: TD had a certain therapeutic effect on cerebral I/R injury. TD with a TR:DH ratio of 1:1 had the best therapeutic effect. Metabolic pathway analysis showed that the protective mechanism of TD against I/R injury involves mainly regulation of brain tissue ADORA2A protein levels and action on the arachidonic acid (AA) pathway. CONCLUSION: TD can ameliorate cerebral I/R injury by regulating ADORA2A degradation in the AA metabolic pathway to attenuate AA metabolic dysfunction and the inflammatory response.

Effect of short-term vitamin D supplementation after nonsurgical periodontal treatment: A randomized, double-masked, placebo-controlled clinical trial.

OBJECTIVES: This trial aimed to evaluate the efficacy and safety of vitamin D supplementation on the residual moderate and deep pockets following nonsurgical periodontal therapy. BACKGROUND: Vitamin D supplementation has potential effects on periodontitis, but current evidence remains inconclusive. METHODS: After 3 months of nonsurgical periodontal treatment, 360 patients with moderate or severe periodontitis were randomly assigned to 2000 international unit (IU)/d vitamin D3, 1000 IU/d vitamin D3, or placebo. Clinical periodontal examinations, including probing depth (PD), bleeding index (BI), plaque index (PLI), attachment loss (AL), and alveolar crest height (ACH), were performed at baseline and after 3 months of intervention. RESULTS: There was a slight but significant decrease in AL and PD in both vitamin D groups compared with placebo group for moderate and deep pockets. About 2000 IU/d vitamin D3 group, 1000 IU/d vitamin D3 group, and placebo group all decreased the AL for both moderate pockets (-0.4 mm vs -0.4 mm vs -0.3 mm) and deep pockets (-1.1 mm vs -1.1 mm vs -1.0 mm) (all P < .05). Similarly, PD was also decreased in these three groups for both moderate pockets and deep pockets (all P < .05). In addition, vitamin D supplementation was well tolerated, and no adverse events were reported. CONCLUSIONS: Although statistically significant differences were observed in favor to vitamin D supplementation, the magnitude of effect size tended to be modest with limited clinical relevance and the long-term efficacy and safety warrant further investigation.

Evaluation of aqueous extracts of Cistanche deserticola as a polysaccharide adjuvant for seasonal influenza vaccine in young adult mice.

Adjuvants can improve the efficacy of influenza vaccines and are still a hot spot in the study and development of influenza vaccines. In this report, the effects of aqueous extracts of Cistanche deserticola (AECD) as a polysaccharide adjuvant on seasonal influenza vaccines (IVV) were explored. The experimental data of anti-IVV IgG1 and IgG as well as hemagglutinin inhibition (HI) titers in young adult mice indicated that IVV intramuscularly co-injected with AECD was significantly more immunogenic than alum-adjuvanted or non-adjuvanted IVV. AECD-adjuvanted vaccine could rapidly initiate specific IgG response. Similarly, IVV with AECD augmented significantly lymphocyte proliferation and increased the positive rates of CD4+, CD8+ and CD44+ T cells from draining lymph nodes and spleens. Importantly, IVV with AECD could induce the Th1 immune response, as indicated by higher IgG2a levels accompanied by the induction of IFN-γ in CD4+ and CD8+ T cells. Additionally, IVV with AECD activated dendritic cells (DCs) and decreased the expression of Treg cells. There were no noticeable side effects after the vaccination. In brief, the addition of AECD enhanced immunogenicity to seasonal influenza vaccine by the induction of HI antibody generation, more rapid humoral immune responses, and a balanced Th1-/Th2-type response, effective T-cell responses, which may be important for seasonal influenza vaccines with broad and long lasting immunity.

Adjuvanticity of aqueous extracts of Artemisia rupestris L. for inactivated foot-and-mouth disease vaccine in mice.

Several methods have been developed to improve the efficacy of foot-and-mouth disease virus (FMDV) vaccine. The study aims to determine whether aqueous extracts of Artemisia rupestris L. (AEAR) as an immunoactivator in combination with inactivated FMDV vaccine can promote immune responses in mice. Intramuscular co-immunization in ICR mice with different doses of AEAR plus FMDV vaccine could substantially improve the FMDV-specific antibody production (IgG, IgG1, and IgG2a) and lead to significant lymphocyte proliferative responses. Th1-type immune responses were also observed, including proliferative responses of CD8+, CD4+, CD4+CD44+, and CD8+CD44+ T cells and the killing efficacy of cytotoxic T lymphocyte (CTL) responses. AEAR also elicited the higher levels of IL-4 and IFN-γ in CD4+ T cells as well as the higher level of IFN-γ in CD8+ T cells. The medium dose of AEAR induced the significant adjuvant activity. Further tests in mice indicated that AEAR could activate DCs maturation by increasing the expression levels of co-stimulatory molecules (CD40, CD86, CD80, and MHC-II) on dendritic cells (DCs) from splenocytes and reduce the activity of regulatory T cells (Treg). Abnormal behaviors, side effects or death were not observed in immunized mice. AEAR could boost humoral and cell-mediated immunity elicited by FMDV vaccine, especially Th1-type immune responses.