Gegen Qinlian tablets delay Alzheimer's disease progression via inhibiting glial neuroinflammation and remodeling gut microbiota homeostasis.

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota. METHODS: The ingredients of GGQLT were analyzed using HPLC-ESI-Q/TOF-MS. The AD model was established by bilateral injection of Aß1-42 into the intracerebroventricular space of rats. The Morris water maze was used to evaluate the cognitive function of the AD rats. The long-term toxicity of GGQLT in rats was assessed by monitoring their body weights and pathological alterations in the liver and kidney. Reactive astrocytes and microglia were assessed by immunohistochemistry by labeling GFAP and Iba-1. The levels of inflammatory cytokines in the hippocampus were evaluated using ELISA kits, RT-PCR, and Western blot, respectively. The potential anti-AD mechanism was predicted by analyses of RNA-sequencing and network pharmacology. Western blot and immunohistochemistry were utilized to detect the phosphorylation levels of IκBα, NF-κB p65, p38, ERK and JNK. The richness and composition of gut bacterial and fungal microflora were investigated via 16S rRNA and ITS sequencing. RESULTS: Typical ingredients of GGQLT were identified using HPLC-ESI-Q/TOF-MS. GGQLT significantly improved the cognitive function of AD rats by suppressing the activation of microglia and astrocytes, improving glial morphology, and reducing the neuroinflammatory reactions in the hippocampus. RNA-sequencing, network and experimental pharmacological studies demonstrated that GGQLT inhibited the activation of NF-κB/MAPK signaling pathways in the hippocampus. GGQLT could also restore abnormal gut bacterial and fungal homeostasis and no longer-term toxicity of GGQLT was observed. CONCLUSIONS: Our findings, for the first time, demonstrate GGQLT exhibit anti-AD effects and is worthy of further exploration and development.

A comprehensive review of the botany, phytochemistry, pharmacology, and toxicology of Murrayae Folium et Cacumen.

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes. Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC. Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master's dissertations were also included. Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer's disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/ß-catenin signaling activity, and upregulating Foxo3a expression. Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

Protective effect of phenylpropionamides in the seed of Cannabis Sativa L. on Parkinson's disease through autophagy.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. As one of the major degradation pathways, autophagy plays a pivotal role in maintaining the effective turnover of proteins and damaged organelles in cells. Lewy bodies composed of α-synuclein (α-syn) abnormally aggregated in the substantia nigra are important pathological features of PD, and autophagy dysfunction is considered to be an important factor leading to abnormal aggregation of α-syn. Phenylpropionamides (PHS) in the seed of Cannabis sativa L. have a protective effect on neuroinflammation and antioxidant activity. However, the therapeutic role of PHS in PD is unclear. In this study, the seeds of Cannabis sativa L. were extracted under reflux with 60% EtOH-H2O, and the 60% EtOH-H2O elution fraction was identified as PHS with the UPLC-QTOF-MS. The 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice was used for behavioral and pharmacodynamic experiments. Behavioral symptoms were improved, Nissl-stained and TH-positive neurons in the substantia nigra were significantly increased in PHS-treated MPTP-induced PD model mice. Compared with the model group, PHS treatment reduced the expression level of α-syn, and the expression of TH increased significantly by western blotting, compared with the model group, the PHS group suppressed Caspase 3 and Bax expression and promoted Bcl-2 expression and levels of p62 decreased significantly, the ratio of LC3-II/I and p-mTOR/mTOR in the PHS group had a downward trend, suggesting that the therapeutic effect of PHS on MPTP-induced PD model mice may be triggered by the regulation of autophagy.

Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders.

Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

Polyacetylenes from Saposhnikovia divaricata and their anticancer activity.

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC50 value of 11.66 µM against HEPG2.

Five new sesquiterpenoids isolated from Dictamnus dasycarpus Turcz.

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC50 values of 3.49 ± 0.10 and 6.42 ± 1.23 µM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 µM.

Efficacy and safety of yoga for the management of chronic low back pain: an overview of systematic reviews.

Background: Yoga is a non-pharmacological conservative therapeutic modality that can be employed for the management of chronic low back pain (CLBP). In this overview, we have summarized and evaluated data from current systematic reviews (SRs) on the use of yoga for CLBP. Methods: We comprehensively searched SRs on the use of yoga for CLBP in nine electronic databases from inception to September 2023. The methodological quality was evaluated using the Assessment of Multiple Systematic Review Scale-2 (AMSTAR-2). The reporting quality of the included SRs was evaluated using the Preferred Reporting Item for Systematic Review and Meta-Analysis-2020 (PRISMA-2020), and the quality of data was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers performed the screening, data extraction, and quality assessment process of SRs. Results: A total of 13 SRs were included. The results of the AMSTAR-2 indicated that the methodological quality of the included studies was relatively low. The PRISMA-2020 checklist evaluation results indicated that methodological limitations in reporting, especially regarding data processing and presentation, were the main weaknesses. The GRADE assessment indicated that 30 outcomes were rated moderate, 42 were rated low level, and 20 were rated very low level. Downgrading factors were mainly due to the limitations of the included studies. Conclusion: Yoga appears to be an effective and safe non-pharmacological therapeutic modality for the Management of CLBP. Currently, it may exhibit better efficacy in improving pain and functional disability associated with CLBP. However, the methodological quality and quality of evidence for SRs/MAs in the included studies were generally low, and these results should be interpreted cautiously.

TFIIB-Related Protein BRP5/PTF2 Is Required for Both Male and Female Gametogenesis and for Grain Formation in Rice.

Transcription factor IIB (TFIIB) is a general transcription factor for RNA polymerase II, exerting its influence across various biological contexts. In the majority of eukaryotes, TFIIB typically has two homologs, serving as general transcription factors for RNA polymerase I and III. In plants, however, the TFIIB-related protein family has expanded greatly, with 14 and 9 members in Arabidopsis and rice, respectively. BRP5/pollen-expressed transcription factor 2 (PTF2) proteins belong to a subfamily of TFIIB-related proteins found only in plants and algae. The prior analysis of an Arabidopsis atbrp5 mutant, characterized by a T-DNA insertion at the 5' untranslated region, demonstrated the essential role of BRP5/PTF2 during the process of pollen germination and embryogenesis in Arabidopsis. Using a rice transformation system based on CRISPR/Cas9 technology, we have generated transgenic rice plants containing loss-of-function frameshift mutations in the BRP5/PTF2 gene. Unlike in the Arabidopsis atbrp5 mutant, the brp5/ptf2 frameshift mutations were not transmitted to progeny in rice, indicating an essential role of BRP5/PTF2 in both male and female gamete development or viability. The silencing of rice BRP5/PTF2 expression through RNA interference (RNAi) had little effect on vegetative growth and panicle formation but strongly affected pollen development and grain formation. Genetic analysis revealed that strong RNAi silencing of rice BRP5/PTF2 was still transmissible to progeny almost exclusively through female gametes, as found in the Arabidopsis atbrp5 knockdown mutant. Thus, reduced rice BRP5/PTF2 expression impacted pollen preferentially by interfering with male gamete development or viability. Drawing upon these findings, we posit that BRP5/PTF2 assumes a distinct and imperative function in the realm of plant sexual reproduction.

Terpenoid compounds from the fruits of Solanum virginianum.

Eleven compounds were isolated and identified from ethanolic extracts of Solanum virginianum fruits, including two new compounds (1-2) and nine known compounds (3-11). Their structures were determined to be melongenaterpene C15-O-ß-D-glucopyranoside (1), (9Z)-3,7,11,15-tetramethyl -hexadeca-1,6,10-triene-3,5,14,15-tetraol-5-O-ß-D-glucopyranoside (2), actini-dioionoside A (3), byzantionoside B (4), citroside A (5), 7Z-roseoside (6), matenoside A (7), megastigmane (8), dihydrophaseic acid 3'-O-ß-D-glucopyranoside (9), taraxerol (10), and huzhangoside C (11). In this paper, NMR spectroscopy was used to study the structures of the compounds, comparing their data with those in the literature. In addition, the potential anti-inflammatory activity of the compounds was also evaluated using the RAW264.7 cell inflammation model induced by lipopolysaccharide (LPS). The terpenoids showed no significant anti-inflammatory activity.

Sodium-glucose cotransporter 2 inhibitor canagliflozin alleviates vascular calcification through suppression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome.

AIMS: Vascular calcification (VC) is prevalent in pathological processes such as diabetes, chronic kidney disease (CKD), and atherosclerosis, but effective therapies are still lacking by far. Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, has been approved for the treatment of type 2 diabetes mellitus and exhibits beneficial effects against cardiovascular disease. However, the effect of CANA on VC remains unknown. In this study, we hypothesize that CANA protects against VC. METHODS AND RESULTS: Micro-computed tomography analysis and alizarin red staining revealed that CANA treatment prevented aortic calcification in CKD rats and in VitD3-overloaded mice. Moreover, CANA alleviated the calcification of rat and human arterial rings. Alizarin red staining revealed that calcification of rat and human vascular smooth muscle cells (VSMCs) was attenuated by CANA treatment and this phenomenon was confirmed by calcium content assay. In addition, CANA downregulated the expression of osteogenic differentiation markers Runx2 and BMP2. Of interest, qPCR and western blot analysis revealed that CANA downregulated the expression of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and the downstream signalling molecules Caspase-1 and IL-1ß in VSMCs as well. Both NLRP3 inhibitor MCC950 and knockdown of NLRP3 by siRNA independently resulted in decreased calcification of VSMCs. By contrast, activation of NLRP3 exacerbated VSMC calcification, and this effect was prevented by the addition of CANA. CONCLUSIONS: Our study for the first time demonstrates that CANA exerts a protective effect on VC at least partially via suppressing the NLRP3 signalling pathway. Therefore, supplementation of CANA as well as inhibition of NLRP3 inflammasome presents a potential therapy for VC.

New compounds from the stems of Fissistigma acuminatissimum Merr. and their in vitro anti-inflammatory activity.

Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.

Phenylpropanoids from Solanum capsicoides and their anti-inflammatory activity.

Two new phenylpropanoids, 4-O-(1''-O-cis-caffeoyl)-ß-glucopyran osyl-1-allyl-3-methoxy-benzene (1), 4'-O-(1''-O-cis-caffeoyl)-ß-glucopyranosyl-hydroxymegastigm-4-en-3-one (2), together with nine known compounds were obtained from the leaves of Solanum capsicoides. Their structures were elucidated based on spectroscopic methods, and comparing spectral data with those in literature. Meanwhile, their anti-inflammatory activities were evaluated on (LPS)-induced RAW 246.7 cells, and 1, 9, and 10 showed better inhibitory effects with IC50 values of 17.19 ± 1.12, 18.15 ± 0.47, and 19.8 ± 0.95 µM, respectively.

Authentication of Bistortae Rhizoma and its three adulterants based on their macroscopic morphology and microscopic characteristics.

Bistortae Rhizoma (Quanshen), a dried rhizome of Polygonum bistorta L., is edited in Chinese Pharmacopiea as only one of species of Polygonum. There are many adulterants were used as Quanshen such as "Eryeliao," "Taipingyangliao" and "Daogenliao" because of its remarkable functions. Previous researches had shown that there were not significant differences among them. Therefore, it is necessary to conduct a comprehensive authentication of these herbs samples. Analyses of the microscopic features of the powders and transverse sections of herbs are the most significant measures of accreditation of the quality of traditional Chinese medicine. In this study, microscopic observation of powders of the herbs and cross-sectional tissues were performed by using common light microscopy, polarized light microscopy and combining PCA analysis to identify Quanshen and three adulterants. We found that calcium oxalate clusters can be a good microscopic marker index to distinguish Quabshen and Eryeliao. In addition, Quanshen and the other two can be further distinguished by the characteristics of cork layer cells and vascular bundles on transverse section of the rhizome. Our results showed that the approach, microscopic features and digital characterization, is efficient, convenient, and reliable.

Acupuncture treatment of facial spasm: An overview of systematic reviews.

BACKGROUND: To provide evidence, this review evaluated the methodological quality, risk of bias, and reporting quality of SRs/MAs in the treatment of Facial Spasm with acupuncture. METHODS: Systematic reviews and Meta analyses (SRs/MAs) of acupuncture for Facial Spasm were retrieved from 8 databases from inception to October 1, 2022. Two reviewers independently screened the literature and extracted the data, then used Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Bias Risk in Systematic Review (ROBIS), and Preferred Report Item for Systematic review and Meta-analysis (PRISMA), Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess methodological quality, risk of bias, quality of reporting, and quality of evidence. RESULTS: A total of 8 SRs/meta-analyses were included. All the SRs were published between 2012-2022. Based on AMSTAR-2, 8 SRs were rated critically low quality. By using the ROBIS tool, 6 SRs were rated low-risk bias. With the PRISMA-A checklist, we found 2 out of 8 SRs were found adequately reported over 70%. With the GRADE system, no high-quality evidence was found, and only two outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by publication bias, inconsistency, and imprecision. CONCLUSION: Acupuncture is a promising complementary treatment for HFS. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

Efficacy and safety of Yaobitong capsule for acute lumbar disc herniation: A protocol for a multi-center randomized controlled trial.

BACKGROUND: There are few effective conservative therapies for acute lumbar disc herniation (LDH), and the choice of nonsteroidal anti-inflammatory drugs is not recommended for all patients. The purpose of this study was to compare the effect of Yaobitong capsule with celecoxib capsule, and to further confirm the safety and efficacy of Yaobitong capsule. METHODS: This study is a large sample multicenter randomized controlled trial. Eight hospitals served as sub centers to recruit patients. A total of 258 patients are divided into Yaobitong group and celecoxib group according to the ratio of 1:1. Celecoxib or Yaobitong capsule was taken orally for 14 days. Patients will complete the trial after 3 months of follow-up, and independent statisticians who are blinded to random assignment will analyze the data using SAS 9.3 software. The primary outcome was the visual analogue scale (VAS) score after 14 days of treatment, and Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and SF-12 will be regarded as secondary outcomes. Safety indexes will be recorded before and after treatment, and adverse events (AEs) will be recorded throughout this trial. DISCUSSION: This study will evaluate the efficacy and safety of Yaobitong capsule in treating LDH. The experimental results will provide evidence support to treat LDH with Yaobitong capsule.

Mantuoluosides A-H, new steroids isolated from the leaves of Datura stramonium L.

Eight new steroids, designated mantuoluosides A-H (1-8), were obtained from the enrichment of steroids of the Datura stramonium L. using HPD-BJQH macroporous resin. Their respective structures were elucidated based on spectroscopic methods and comparison data with literature. The anti-inflammatory activities of these compounds were evaluated on (LPS)-induced RAW264.7 cells with inhibition ratio. It was found that most isolates showed potential anti-inflammatory activity with varying degrees of inhibition rate in a concentration-dependent manner at non-cytotoxic concentrations.

Inositol Derivatives with Anti-Inflammatory Activity from Leaves of Solanum capsicoides Allioni

Eight new inositol derivatives, solsurinositols A-H (1-8), were isolated from the 70% EtOH extract of the leaves of Solanum capsicoides Allioni. Careful isolation by silica gel column chromatography followed by preparative high-performance liquid chromatography (HPLC) allowed us to obtain analytically pure compounds 1-8. They shared the same relative stereochemistry on the ring but have different acyl groups attached to various hydroxyl groups. This was the first time that inositol derivatives have been isolated from this plant. The chemical structures of compounds 1-8 were characterized by extensive 1D nuclear magnetic resonance (NMR) and 2D NMR and mass analyses. Meanwhile, the in vitro anti-inflammatory activity of all compounds was determined using lipopolysaccharide (LPS)-induced BV2 microglia, and among the isolates, compounds 5 (IC50 = 11.21 ± 0.14 µM) and 7 (IC50 = 14.5 ± 1.22 µM) were shown to have potential anti-inflammatory activity.

Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification.

Vascular calcification is a common pathologic condition in patients with chronic kidney disease (CKD). Cell death such as apoptosis plays a critical role in vascular calcification. Ferroptosis is a type of iron-catalyzed and regulated cell death resulting from excessive iron-dependent reactive oxygen species and lipid peroxidation. However, it is unclear whether ferroptosis of vascular smooth muscle cells (VSMCs) regulates vascular calcification in CKD. Our results showed that high calcium and phosphate concentrations induced ferroptosis in rat VSMCs in vitro. Inhibition of ferroptosis by ferrostatin-1 dose-dependently reduced mineral deposition in rat VSMCs under pro-osteogenic conditions, as indicated by alizarin red staining and quantification of calcium content. In addition, gene expression analysis revealed that ferrostatin-1 inhibited osteogenic differentiation of rat VSMCs. Similarly, ferrostatin-1 remarkably attenuated calcification of rat and human arterial rings ex vivo and aortic calcification in vitamin D3-overloaded mice in vivo. Moreover, inhibition of ferroptosis by either ferrostatin-1 or deferoxamine attenuated aortic calcification in rats with CKD. Mechanistically, high calcium and phosphate downregulated expression of SLC7A11 (a cystine-glutamate antiporter), and reduced glutathione (GSH) content in VSMCs. Additionally, GSH depletion induced by erastin (a small molecule initiating ferroptotic cell death) significantly promoted calcification of VSMCs under pro-osteogenic conditions, whereas GSH supplement by N-acetylcysteine reduced calcification of VSMCs. Consistently, knockdown of SLC7A11 by siRNA markedly promoted VSMC calcification. Furthermore, high calcium and phosphate downregulated glutathione peroxidase 4 (GPX4) expression, and reduced glutathione peroxidase activity. Inhibition of GPX4 by RSL3 promoted VSMC calcification. Thus, repression of the SLC7A11/GSH/GPX4 axis triggers ferroptosis of VSMCs to promote vascular calcification under CKD conditions, providing a novel targeting strategy for vascular calcification.

Downregulation of HDAC9 by the ketone metabolite ß-hydroxybutyrate suppresses vascular calcification.

Vascular calcification is an actively regulated process resembling bone formation and contributes to the cardiovascular morbidity and mortality of chronic kidney disease (CKD). However, an effective therapy for vascular calcification is still lacking. The ketone body ß-hydroxybutyrate (BHB) has been demonstrated to have health-promoting effects including anti-inflammation and cardiovascular protective effects. However, whether BHB protects against vascular calcification in CKD remains unclear. In this study, Alizarin Red staining and calcium content assay showed that BHB reduced calcification of vascular smooth muscle cells (VSMCs) and arterial rings. Of note, compared with CKD patients without thoracic calcification, serum BHB levels were lower in CKD patients with thoracic calcification. Supplementation with 1,3-butanediol (1,3-B), the precursor of BHB, attenuated aortic calcification in CKD rats and VitD3-overloaded mice. Furthermore, RNA-seq analysis revealed that BHB downregulated HDAC9, which was further confirmed by RT-qPCR and western blot analysis. Both pharmacological inhibition and knockdown of HDAC9 attenuated calcification of human VSMCs, while overexpression of HDAC9 exacerbated calcification of VSMCs and aortic rings, indicating that HDAC9 promotes vascular calcification under CKD conditions. Of note, BHB treatment antagonized HDAC9-induced vascular calcification. In addition, HDAC9 overexpression activated the NF-κB signaling pathway and inhibition of NF-κB attenuated HDAC9-induced VSMC calcification, suggesting that HDAC9 promotes vascular calcification via activation of NF-κB. In conclusion, our study demonstrates that BHB supplementation inhibits vascular calcification in CKD via modulation of the HDAC9-dependent NF-κB signaling pathway. Moreover, we unveil a crucial mechanistic role of HDAC9 in vascular calcification under CKD conditions; thus, nutritional intervention or pharmacological approaches to enhance BHB levels could act as promising therapeutic strategies to target HDAC9 for the treatment of vascular calcification in CKD. © 2022 The Pathological Society of Great Britain and Ireland.

Amidoxime functionalized chitosan for uranium sequestration in vivo.

Amidoxime functionalized chitosan (AC) was recommended as a chelator for uranium sequestration in vivo in this study, and the structure-activity relationship was also explored. Compared with ZnNa3-DTPA, which was a commercial uranium mobilization drug, AC exhibited excellent biocompatibility and uranium removal efficiency, whether by injection or orally, which could reduce the amounts of uranium deposited in kidneys and femurs by up to 43.6% and 32.3%. In particular, ACs still possessed the ability to mobilize uranium in vivo even if administration was delayed for 72 h.