A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Variability in performance of genetic-enhanced DXA-BMD prediction models across diverse ethnic and geographic populations: A risk prediction study.

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations. METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10-6 and 5×10-7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P < 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors. CONCLUSIONS: In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10-6 or 5×10-7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the model's explanatory power. The study highlights the need for training models on diverse populations to improve predictive performance across various ethnic and geographical groups.

Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis.

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets-human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)-were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.

[Evaluation of nutritional value of Bambusae Concretio Silicea based on content of 15 amino acids].

The content of 15 total amino acids(TAAs) in Bambusae Concretio Silicea was determined by HPLC with phenyl-isothiocyanate(PITC) for pre-column derivatization. The results showed that the content of TAA was 0.61-12.25 mg·g~(-1), and aspartic acid(Asp), glutamic acid(Glu), proline(Pro), glycine(Gly), and valine(Val) were the top five amino acids in terms of the average content. The content of essential amino acids(EAAs), conditionally essential amino acids(CEAAs), non-essential amino acids(NEAAs), and medicinal amino acids(MAAs) was 0.24-4.75, 0.30-4.73, 0.40-7.50, and 0.36-6.51 mg·g~(-1), respectively. Among the delicious amino acids, sweet amino acids(SAA), bitter amino acids(BAA), fresh-taste amino acids(FAAs), and odourless amino acids(OAAs) had the content of 0.22-4.70, 0.19-4.03, 0.13-2.26, and 0.06-1.26 mg·g~(-1), respectively. The 21 batches of Bambusae Concretio Silicea samples presented the same composition but significant differences in the content of amino acids. Among the three producing areas, Guangdong was the area where the samples had the highest content of TAAs, EAAs, CEAAs, NEAAs, MAAs, and delicious amino acids. Furthermore, the ratio of amino acid(RAA), ratio coefficient of amino acid(RCAA), and score of ratio coefficient of amino acid(SRCAA) were calculated to evaluate the nutritional value of Bambusae Concretio Silicea. The results showed that the Bambusae Concretio Silicea samples from Guangdong had better nutritional value. The nutritional value evaluation based on the content of 15 amino acids was proposed to provide data support for the quality grading of Bambusae Concretio Silicea and lay a foundation for the development and utilization of the medicinal material resources.

Effects of Curing Defects in Adhesive Layers on Carbon Fiber-Quartz Fiber Bonded Joint Performance.

Due to their mechanical load-bearing and functional wave transmission, adhesively bonded joints of carbon fiber-quartz fiber composites have been widely used in the new generation of stealth aviation equipment. However, the curing defects, caused by deviations between the process environment and the setting parameters, directly affect the service performance of the joint during the curing cycle. Therefore, the thermophysical parameter evolution of adhesive films was analyzed via dynamic DSC (differential scanning calorimeter), isothermal DSC and TGA (thermal gravimetric analyzer) tests. The various prefabricating defects within the adhesive layer were used to systematically simulate the impacts of void defects on the tensile properties, and orthogonal tests were designed to clarify the effects of the curing process parameters on the joints' bonding performance. The results demonstrate that the J-116 B adhesive film starts to cure at a temperature of 160 °C and gradually forms a three-dimensional mesh-bearing structure. Furthermore, a bonding interface between the J-116 B adhesive film and the components to be connected is generated. When the curing temperature exceeds 200 °C, both the adhesive film and the resin matrix thermally degrade the molecular structure. The adhesive strength weakens with an increasing defect area ratio and number, remaining more sensitive to triangle, edge and penetration defects. By affecting the molecular structure of the adhesive film, the curing temperature has a significant impact on the bonding properties; when the curing degree is ensured, the curing pressure directly impacts the adhesive's performance by influencing the morphology, number and distribution of voids. Conversely, the heating rate and heat preservation time have minimal effects on the bonding performance.

Experimental Study on the Diffusion Law of Coal-Based Solid Waste Slurry with Grouting Filling in the Gangue Voids of the Caving Zone.

Due to the concealment of the caving zone, it is difficult to detect and grasp the diffusion law of the slurry in the voids of the gangue pile. On the preparation of reasonable grouting filling materials, a large-scale three-dimensional gangue grouting filling test system has been established to detect the slurry pressure and resistivity inside the gangue pile and analyze the flow pattern of the slurry in the voids of the gangue pile. The research results show that the slump and bleeding rate of the filling slurry are significantly reduced with the increase of the fly ash content. The optimal ratio of fly ash, coal gangue, and gasification slag is 7:2:1, with a mass fraction of 72%. In the process of grouting, the internal pressure of the gangue pile can be divided into the initial stable stage, the step growth stage, and the pressure stability stage, and the change curve of the pressure sensor at the lower level is similar. The resistance value of the original broken gangue in the experiment is approximately 1600 Ω. Grouting filling forms a slurry-rock mixture, and its resistance continuously decreases with the stable injection of the slurry (minimum value 150 Ω). It is determined that the slurry near the grouting hole mainly diffuses longitudinally with a good void filling effect. The void channels of slurry diffusion are randomly distributed and have different shapes, which hinder slurry flow and diffusion. Slurry particles accumulate and settle at local small voids. Meanwhile, the surface of the gangue blocks is dry, and the slurry absorbs part of the water during diffusion, resulting in the increase of the slurry concentration and the weakening of the lateral diffusion ability. Secondary or multiple grouting can effectively fill the void of the broken gangue and further improve the filling effect.

Inferring Causal Relationships Between Metabolites and Polycystic Ovary Syndrome Using Summary Statistics from Genome­Wide Association Studies.

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Previous studies have suggested that metabolites may play a pivotal mediating role in the progression of phenotypic variations. Although several metabolites had been identified as potential markers for PCOS, the relationship between blood metabolites and PCOS was not comprehensively explored. Previously, Pickrell et al. designed a robust approach to infer evidence of a causal relationship between different phenotypes using independently putative causal SNPs. Our previous paper extended this approach to make it more suitable for cases where only a few independently putative causal SNPs were identified to be significantly associated with the phenotypes (i.e., metabolites). When the most significant SNPs in each independent locus (the independent lead SNPs) with p-values of < 1 × 10-5 were used, 3 metabolites (2-tetradecenoyl carnitine, threitol, 1-docosahexaenoylglycerophosphocholine) causally influencing PCOS and 2 metabolites (asparagine and phenyllactate) influenced by PCOS were identified, (relative likelihood r < 0.01). Under a less stringent threshold of r < 0.05, 7 metabolites (trans-4-hydroxyproline, glutaroyl carnitine, stachydrine, undecanoate, 7-Hoca, N-acetylalanine and 2-hydroxyisobutyrate) were identified. Taken together, this study can provide novel insights into the pathophysiological mechanisms underlying PCOS; whether these metabolites can serve as biomarkers to predict PCOS in clinical practice warrants further investigations.

Detection of NPM1 Mutations in Acute Myeloid Leukemia by using Drop-Off Droplet Digital PCR and its Clinical Application.

BACKGROUND: Nucleophosmin 1 (NPM1) mutations, which occur in 25 - 30% of acute myeloid leukemia (AML) and 50 - 60% of AML with normal karyotype, have been identified as an important marker for stratification of prog-nosis in AML. This study aimed to establish a new quantitative polymerase chain reaction (PCR) technique, the drop-off droplet digital PCR (ddPCR), for rapid and sensitive detection of NPM1 mutations in AML. METHODS: We established the drop-off ddPCR system and verified its performance. NPM1 mutations were screened in 130 AML patients by drop-off ddPCR and were validated by Sanger sequencing and next-generation sequencing (NGS). Then, the NPM1 mutation burden was dynamically monitored in five patients. RESULTS: The limit of blank (LOB) of drop-off ddPCR established for NPM1 mutation was 3.36 copies/µL, and the limit of detection (LOD) was 5.00 - 5.37 copies/µL in 50 ng DNA, and the sensitivity was about 0.05%, which had good linearity. Drop-off ddPCR identified 33/130 (25.4%) NPM1 mutated cases, consistent with Sanger sequencing. In 18 NPM1 positive cases selected randomly, NGS identified fourteen with type A mutation, two with type D mutation, and two with rare type mutations. The mutation burden of NPM1 mutation analyzed by NGS was consistent with the drop-off ddPCR. The sequential samples were detected for measurable residual disease (MRD) monitoring in 5 patients showed that the NPM1 mutation burden was consistent with clinical remission and recurrence. Compared with traditional ddPCR, drop-off ddPCR was also suitable for MRD monitoring. CONCLUSIONS: In this study, we established a drop-off ddPCR method for detecting three common mutations in AML with good sensitivity and repeatability, which can be used to screen mutations in newly diagnosed AML patients and for MRD monitoring after remission to guide treatment.

Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.

Functional Enrichment Analysis Identifying Regulatory Information Associated with Human Fracture.

Dozens of loci associated with fracture have been identified by genome-wide association studies (GWASs). However, most of these variants are located in the noncoding regions including introns, long terminal repeats, and intergenic regions. Although combining regulation information helps to identify the causal SNPs and interpret the involvement of these variants in the etiology of human fracture, regulation information which was truly associated with fracture was unknown. A novel functional enrichment method GARFIELD (GWAS Analysis of Regulatory of Functional Information Enrichment with LD correction) was applied to identify fracture-associated regulation information, including transcript factor binding sites, expression quantitative trait loci (eQTLs), chromatin states, enhancer, promoter, dyadic, super enhancer and Epigenome marks. Fracture SNPs were significantly enriched in exon (Bonferroni correction, p value < 7.14 × 10-3) at two GWAS p value thresholds through GARFIELD. High level of fold-enrichment was observed in super enhancer of monocyte and the enhancer of chondrocyte (Bonferroni correction, p value < 4.45 × 10-3). eQTLs of 44 tissues/cells and 10 transcription factors (TFs) were identified to be associated with human fracture. These results provide new insight into the etiology of human fracture, which might increase the identification of the causal SNPs through the fine-mapping study combined with functional annotation, as well as polygenic risk score.

Comparisons of facial emotion recognition in different social contexts among patients with schizophrenia, major depressive disorder and bipolar disorder.

BACKGROUND: Previous studies have found that patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD) all have facial emotion recognition deficits, but the differences and similarities of these deficits in the three groups of patients under different social interaction situations are not clear. The present study aims to compare the ability of facial emotion recognition in three different conversation situations from a cross-diagnostic perspective. METHODS: Thirty-three participants with SCZ, 35 participants with MDD, and 30 participants with BD were recruited, along with 31 healthy controls. A computer-based task was given to assess the ability of Facial Emotion Categorization (FEC) under three different conversational situations (praise, blame, and inquiry). RESULTS: In the "praise" situation, patients with SCZ, MDD and BD were all slower to recognize anger emotion than the healthy controls. In all three clinical groups, patients with SCZ recognized angry faces faster than those with MDD and BD on a continuum from happy faces to angry faces in the "inquiry" situation, while no significant difference was found in the latter two groups. In addition, no significant defect was found in the percentage and threshold of angry face recognition in all three patient groups. CONCLUSIONS: Our findings indicate that patients with SCZ, MDD, and BD share both common and distinct deficits in facial emotion recognition during social interactions, which may be beneficial for early screening and precise intervention for these mental disorders.

Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway / 中国中药杂志

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Chemical constituents in Dolomiaea plants and their pharmacological activities: a review / 中国中药杂志

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.

Expression of high-mobility group B1 released by exosome in nonalcoholic fatty liver disorder and regulated by TLR4 signal / 解放军医学杂志

Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.

Correlation between carotid atherosclerosis stenotic severity and myocardial infarction size assessed by carotid color ultrasonography / 心血管康复医学杂志

Objective:To study correlation between carotid atherosclerosis(AS)stenotic severity and myocardial infarction(MI)size assessed by carotid color ultrasonography.Methods:According to infarction size,a total of 180 MI patients trea-ted in our hospital were divided into focal necrosis group(n=92),small-medium size infarction group(n=45)and large size infarction group(n=43).Carotid artery stenosis,peak systolic flow velocity(PSV),end diastolic flow velocity(EDV),number of AS plaques and MI location were compared among all group.And correlation between carotid AS ste-notic severity and MI size was analyzed.Results:Compared with focal necrosis group,there were significant reductions in PSV[(101.43±23.16)cm/s vs.(154.35±65.73)cm/s vs.(325.19±105.27)cm/s]and EDV[(34.19±19.36)cm/s vs.(77.13±20.61)cm/s vs.(138.41±84.93)cm/s]in small-medium size infarction group and large size infarction group,and above indexes of large size infarction group were significantly higher than those of small-medium size infarction group(P=0.001 all).Compared with focal necrosis group and small-medium size infarction group,there were significant rise in percentages of severe carotid stenosis(4.35%,11.11%vs.37.27%),occlusion(1.09%,4.44%vs.27.91%),number of atherosclerotic plaque＞2(38.04%,40.00%vs.65.12%)and anterior infarction(32.61%,35.56%vs.69.77%),and significant reduction in percentage of posterior infarction(48.91%,44.44%vs.23.26%)in large size infarction group(P＜0.05 or＜0.01).Spearman correlation analysis indicated that carotid AS stenotic severity was significant positively cor-related with MI size(r=0.733,P=0.001).Conclusion:Incidence rates of severe carotid stenosis and occlusion are higher in patients with large size myocardial infarction.Carotid AS stenotic severity is significant positively correlated with myo-cardial infarction size,which possesses certain application value in detecting myocardial infarction.

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Textual research on Bambusae Concretio Silicea / 中国中药杂志

By studying various ancient texts such as herbal classics and medical literature from different eras, it was found that there were discrepancies in the records about Bambusae Concretio Silicea(Tian Zhu Huang). In order to establish an accurate foundation, this research was based on ancient herbal literature and combined with plant morphology and investigative studies to examine its earliest mentions in ancient texts, nomenclature, medicinal properties, indications, and quality assessment standards. In the early records, Bambusae Concretio Silicea was referred to by several different names, such as "Zhu Huang" "Tian Zhu Huang" "Zhu Gao" "Zhu Tang", and "Zhu Huang". The earliest known formal usage of the name "Tian Zhu Huang" was found in the book Ri Hua-zi's Materia Medica(Ri Hua Zi Ben Cao). Throughout various ancient texts, the earliest recorded information about Bambusae Concretio Silicea also appeared in Ri Hua-zi's Materia Medica, not in Materia Medica of Sichuan(Shu Ben Cao) or other ancient texts. Ri Hua-zi's Materia Medica provided relevant descriptions of its origin, medicinal properties, and indications, albeit with some errors due to limited knowledge. However, this has been a valuable starting point for future research on Bambusae Concretio Silicea and holds pioneering significance in forming a mature system. As the research delved deeper, the medicinal properties of Bambusae Concretio Silicea have been consistent since Ri Hua-zi's Materia Medica, and the understanding has gradually improved through years of clinical verification. During the investigation process, the authors found limited records on the quality evaluation of Bambusae Concretio Silicea in ancient texts. Although the information is scarce, it serves as a foundational basis for establishing corresponding quality grading standards for Bambusae Concretio Silicea in the future.

Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis and Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer.@*METHODS@#Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases.@*RESULTS@#A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts.@*CONCLUSIONS@#This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.