Pan-cancer scRNA-seq analysis reveals immunological and diagnostic significance of the peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMCs) reflect systemic immune response during cancer progression. However, a comprehensive understanding of the composition and function of PBMCs in cancer patients is lacking, and the potential of these features to assist cancer diagnosis is also unclear. Here, the compositional and status differences between cancer patients and healthy donors in PBMCs were investigated by single-cell RNA sequencing (scRNA-seq), involving 262,025 PBMCs from 68 cancer samples and 14 healthy samples. We observed an enhanced activation and differentiation of most immune subsets in cancer patients, along with reduction of naïve T cells, expansion of macrophages, impairment of NK cells and myeloid cells, as well as tumor promotion and immunosuppression. Based on characteristics including differential cell type abundances and/or hub genes identified from weight gene co-expression network analysis (WGCNA) modules of each major cell type, we applied logistic regression to construct cancer diagnosis models. Furthermore, we found that the above models can distinguish cancer patients and healthy donors with high sensitivity. Our study provided new insights into using the features of PBMCs in non-invasive cancer diagnosis.

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria.

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

Structural characterization of polysaccharide from the peel of Trichosanthes kirilowii Maxim and its anti-hyperlipidemia activity by regulating gut microbiota and inhibiting cholesterol absorption.

The peel of Trichosanthes kirilowii Maxim, is considered one of the primary sources for Trichosanthis pericarpium in traditional Chinese medicine, exhibiting lipid-lowering properties. The impact on hyperlipidemia mice of the crude polysaccharide from the peel of T. Kirilowii (TRP) was investigated in this study. The findings revealed that TRP exhibited a significant improvement in hepatic lipid deposition. Moreover, it significantly decreased serum levels of TC, TG, and LDL-C, while concurrently increasing HDL-C. 16S rRNA amplicon sequencing technique revealed that TRP group exhibited an increased relative abundance of Actinobacteria, a down-regulated relative abundance of Ruminiclostridium, and an up-regulated relative abundance of Ileibacterium. Therefore, TRP might play a role in anti-hyperlipidemia through regulation of the intestinal milieu and enhancement of microbial equilibrium. Consequently, targeted fractionation of TRP resulted in the isolation of a homogeneous acidic polysaccharide termed TRP-1. The TRP-1 polysaccharide, with an average molecular weight of 1.00 × 104 Da, and was primarily composed of Rha, GlcA, GalA, Glc, Gal and Ara. TRP-1 possessed a backbone consisting of alternating connections between â†’ 6)-α-Galp-(1 â†’ 4)-α-Rhap-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ units and branched chain containing â†’ 6)-α-Glcp-(1→, 2,4)-ß-Glcp-(1, and â†’ 4)-α-GlapA-(1→. Both TRP and TRP-1 exhibited significant disruption of cholesterol micelles, highlighting their potential as lipid-lowering agents that effectively inhibit cholesterol absorption pathways.

Joint association of heavy metals and polycyclic aromatic hydrocarbons exposure with depression in adults.

BACKGROUND: Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) represent significant components of environmental pollution, typically occurring as mixtures, raising concerns about their potential impact on human health. However, the combined effect of HMs and PAHs exposure on depression has not been explored. METHODS: Leveraging National Health and Nutrition Examination Survey (NHANES) data spanning 2005 to 2016, we employ survey-weighted multiple logistic regression models to probe the interrelation between HMs, PAHs, and depression. This exploration is complemented by age and gender-stratified analyses, as well as a determination of the dose-response linkage via restricted cubic spline regression. Furthermore, the combined impact of HMs and PAHs on depression was evaluated through a range of statistical methodologies. RESULTS: The study encompasses 7732 adults. Our findings unveil notable associations, indicating the significant influence of cadmium (Cd), lead (Pb), and all six PAHs metabolites on depression. Moreover, mixed exposure to HMs and PAHs emerges as a substantial contributor to an augmented depression risk, with Cd, Pb, 1-hydroxynaphthalene (1-NAP), 2-hydroxyfluorene (2-FLU), and 1-hydroxypyrene (1-PYR) likely driving this positive relationship. Intriguingly, subgroup analyses highlight greater prominence of these connections among individuals aged 20-59 and among women. Furthermore, the results tentatively suggest a potential interplay between Cd and 2-NAP in relation to depression. CONCLUSION: This study posits that exposure to both individual and combined HMs and PAHs may be associated with an elevated risk of depression. Further prospective investigations are warranted to substantiate these findings.

Relationship between autism and brain cortex surface area: genetic correlation and a two-sample Mendelian randomization study.

BACKGROUND: Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA. METHODS: Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans). We used Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS) to calculate the heritability of each trait. As for the genetic correlation between ASD and SA, LDSC was used for global correlation and HESS was used to examine the local genetic covariance further. We used three Mendelian randomization (MR) methods, Inverse-variance weighted, MR-Egger, and weighted median to estimate the causal relationship. RESULTS: LDSC observed a nominal significant genetic correlation (rg = 0.1229, P-value = 0.0346) between ASD and SA of the rostral anterior cingulate gyrus whereas analysis through HESS did not reveal any significant loci having genetic covariance. Based on MR results, statistically meaningful estimations were found in the following areas, postcentral cortex (ß (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, PIVW = 5.38 × 10- 3, PFDR = 3.09 × 10- 2), posterior cingulate gyrus (ß (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, PIVW = 2.05 × 10- 2, PFDR = 4.26 × 10- 2), supramarginal gyrus (ß (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, PIVW = 2.24 × 10- 2, PFDR = 4.31 × 10- 2). CONCLUSION: Our results provided genetic evidence to support the opinion that individuals with ASD tend to develop differences in cortical SA of special areas. The findings contributed to understanding the genetic relationship between ASD and cortical SA.

Phytochemical analysis of different Callicarpa species based on integrating metabolomics and chemometrics.

INTRODUCTION: Traditionally, Callicarpa species have been utilized their anti-inflammatory and hemostatic properties. Prominently featured species in the 2020 Edition of the Chinese Pharmacopoeia were Callicarpa nudiflora (CN), Callicarpa macrophylla (CM), Callicarpa formosana (CF), and Callicarpa kwangtungensis (CK), which were formulated into several medicinal preparations. Extensive applications led to the significant depletion of CN's wild resources. The management of germplasm resources was significantly disordered. Adulteration issues were also prevalent. OBJECTIVE: It is imperative that the study aims to identify alternative sources for CN and other pharmacopeial varieties and develop methods to distinguish different Callicarpa species. RESULTS: Data were acquired using three mass spectrometry modes: Data Dependent Analysis (DDA), Data-Independent Analysis (DIA), and full mass spectrometry (MS). The DDA mode identified or inferred information on 54 compounds. The Full MS mode identified or inferred 74 compounds, including 20 that were previously unreported in Callicarpa. These compounds were confirmed using standards. The DIA mode did not facilitate identification due to missing precursor ion data. With metabolomics, 19 differential compounds were identified or inferred. Luteolin, chrysoeriol, and quercetin were selected as potential markers, integrating the 10 active compounds from network pharmacology. CONCLUSION: Based on the relative abundance of these markers, it was proposed that Callicarpa giraldii Hesse ex Rehd. var. (CGHRV) and CM could serve as alternative resource species to CN, while CGHRV and Callicarpa giraldii Hesse ex Rehd. (CGHR) could substitute the pharmacopeial CM. Callicarpa longissimi (CLG) was suggested as an alternative to CK, while Callicarpa cathayana (CC) and Callicarpa rubella (CRL) could replace CF. Furthermore, the absence of certain compounds in CK presented a novel opportunity for the differentiation of various Callicarpa species.

PLTS/ARAS-based financing risk resilience capability evaluation for fisheries enterprise: A case study of green transformation and upgrading.

Clearly delineating the key capabilities of organizational resilience for fisheries enterprises holds significant practical implications, as it can mitigate financing risks and foster the sustainable development of the fisheries industry. Based on the "dynamic capabilities perspective", this study constructs an analytical framework for the resilience capabilities of fisheries enterprises against financing risk. A hybrid method comprising the probabilistic linguistic term set, the decision-making trial and evaluation laboratory, and the additive ratio assessment is applied to a case study of Homey Group, examining the diverse pathways through which financing risk forms and impacts outcomes. The main findings are: (1) In the comprehensive assessment of the role of resilience capabilities in addressing the "Risk-Seeking-Decline Type" financing risk factors, market diversification and sustainable practices are accorded higher weights surpassing financial resources as the two most value-enhancing resilience capabilities. Enterprises characterized by a "Risk-Seeking-Loss Type" profile tend to assign higher weights to market diversification and technological infrastructure when evaluating financing risk resilience capabilities. (2) Regarding the key capabilities of organizational resilience, Homey Group possesses a weak risk management system for monitoring and evaluating significant risks and implementing control activities. (3) With regards to suggestions for improvement, it is advisable to delegate oversight of the risk identification process to a designated risk committee or specialists in risk management. The conclusions contribute to a deeper understanding of the nature and mechanism of resilience capabilities for fisheries enterprises and provides implications for risk management and sustainable development.

Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.

BACKGROUND: Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. METHODS: Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran's Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. RESULTS: The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, PIVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, PIVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, PIVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive-compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis. CONCLUSIONS: In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders.

[Variations of glucose content in Massa Medicata Fermentata during processing based on quantitative proton nuclear magnetic resonance].

A quantitative proton nuclear magnetic resonance(qHNMR) method was established to determine the glucose content in commercially available Massa Medicata Fermentata(MMF) products and explore the variations of glucose content in MMF products during processing. The qHNMR spectrum of MMF in deuterium oxide was obtained with 2,2,3,3-d_4-3-(trimethylsilyl) propionate sodium salt as the internal standard substance. With the doublet peaks of terminal hydrogen of glucose with chemical shift at δ 4.65 and δ 5.24 as quantitative peaks, the content of glucose in MMF samples was determined. The glucose content showed a good linear relationship within the range of 0.10-6.44 mg·mL~(-1). The relative standard deviations(RSDs) of precision, stability, repeatability, and recovery for determination were all less than 2.3%. The glucose content varied in different commercially available MMF samples, which were associated with the different fermentation days, wheat bran-to-flour ratios, and processing methods. The glucose content in MMF first increased and then decreased over the fermentation time. Compared with the MMF products fermented with wheat bran or flour alone, the products fermented with both wheat bran and flour had increased glucose. The glucose content of bran-fried MMF was slightly lower than that of raw MMF, while the glucose content in charred MMF was extremely low. In conclusion, the qHNMR method established in this study is simple, fast, and accurate, serving as a new method for determining the glucose content in MMF. Furthermore, this study clarifies the variations of glucose content in MMF during processing, which can not only indicate the processing degree but also provide a scientific basis for revealing the fermentation mechanism and improving the quality control of MMF.

Interfacial Assembly of Nanocrystals on Nanofibers with Strong Interaction for Electrocatalytic Nitrate Reduction.

One-dimensional fiber architecture serves as an excellent catalyst support. The orderly arrangement of active materials on such a fiber substrate can enhance catalytic performance by exposing more active sites and facilitating mass diffusion; however, this remains a challenge. We developed an interfacial assembly strategy for the orderly distribution of metal nanocrystals on different fiber substrates to optimize their electrocatalytic performance. Using electrochemical nitrate reduction reaction (NO3 - RR) as a representative reaction, the iron-based nanofibers (Fe/NFs) assembly structure achieved an excellent nitrate removal capacity of 2317 mg N/g Fe and N2 selectivity up to 97.2 %. This strategy could promote the rational design and synthesis of fiber-based electrocatalysts.

An innovative extraction strategy for herbal medicine by adopting p-sulphonatocalix[6]/[8]arenes.

INTRODUCTION: Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products. OBJECTIVE: In this study, an innovative method of SC6A/SC8A assisted extraction of the alkaloids from herbs was established. METHODS: SC6A and SC8A were designed to extract 27 alkaloids from seven herbal medicines. Based on the significant solubilisation and extraction effect, Stephaniae Tetrandrae Radix (Fangji, FJ) was selected to obtain the optimal extraction process by adopting single factor test and orthogonal experiment. Then, the alkaloids and SC6A/SC8A were separated by one-step alkalisation and SCnA were reused. The host-guest complexes between alkaloids and SCnA were determined by competitive fluorescence titration, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (1 H-NMR) analysis. RESULTS: The optimum condition for SC6A assisted extraction was 5:1:80 (g/g/mL) for herbs/SC6A/solution ratio, 355-250 µm particle size and ultrasonicate 0.5 h, whilst 10:1:40 (g/g/mL) for herbs/SC8A/solution ratio, 355-250 µm particle size and ultrasonicate 0.5 h for SC8A assisted extraction. The total yield of alkaloids (fangchinoline and tetrandrine) from FJ was increased by 4.87 times and 5.97 times with SC6A and SC8A. Moreover, a good reusability of SC6A/SC8A was achieved by alkalisation dissociation. Host-guest complexes were determined by competitive fluorescence titration at a molar ratio of 1:1 between most alkaloids (25/27, except evodiamine and rutaecarpine) and SC6A/SC8A. The complex structure was proved by DSC, FTIR and 1 H-NMR analysis. CONCLUSION: The study provided an effective eco-friendly and energy-saving extraction method of alkaloids from herbal medicine.

GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma.

BACKGROUND: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas. METHODS: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells. RESULTS: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration. CONCLUSIONS: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

Integrating chemical profiling and network pharmacology analysis based on anti-inflammatory effects for quality control of Scutellaria barbata.

INTRODUCTION: With the wide application of Scutellaria barbata D. Don for hepatitis and mastitis, its quality control issues have also received increasing attention. Based on the multi-component and multi-target characteristics of traditional Chinese medicine, there is an urgent need to establish a quality evaluation system. OBJECTIVES: This study intends to integrate the "quality-activity-quantification" strategy and establish an activity-related quality control method to ensure the safety and effectiveness of S. barbata. MATERIAL AND METHODS: Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was used to characterize the chemical components of S. barbata, and network pharmacological analysis was carried out on the identified components. The index components were determined on the basis of comprehensive activity prediction results and content information. At the same time, the contents of 16 batches of S. barbata from different origins were determined. RESULTS: A total of 94 compounds were identified according to mass spectrometric data, 12 of which were isolated and structure-confirmed by nuclear magnetic resonance technology. Network pharmacological analysis was applied to predict their key targets and the major pathways mediating their anti-inflammatory effects. On the basis of comprehensive activity prediction and content information, five components were chosen as crucial quality indicators of S. barbata, including scutellarin, scutellarein, luteolin, apigenin, and hispidulin. CONCLUSION: In this study, 16 different S. barbata batches were compared, and five quality indicators were determined on the basis of qualitative and activity results. The present study provides useful information for evaluating the quality of S. barbata in different areas, and also provides a new basis for the development of quality evaluation methods.

Determination of Trimethylamine N-oxide and Betaine in Serum and Food by Targeted Metabonomics.

Trimethylamine N-oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at δ 3.29 and δ 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.

Oriented-Redox Induced Uniform MnO2 Coating on Ni3S2 Nanorod Arrays as a Stable Anode for Enhanced Performances of Lithium Ion Battery.

Cost-effective transition metal chalcogenides have aroused wide consideration as alternative anode materials in lithium ion batteries (LIBs) on account of their elevated lithium activity and considerable theoretical capacity. However, the significant challenge caused by the large volume change and shuttle effect of polysulfides during Li ion insertion/extraction severely restricts their practical application. In this work, the uniform MnO2 coating layer with a tunable thickness on Ni3S2 nanorod arrays has been achieved through a mild oriented-redox reaction by taking advantage of the mixing valence of Ni in Ni3S2 [(Ni2+)2(Ni0)(S2-)2]. The core/shell structured nanorod arrays directly used as anode materials of LIBs demonstrate remarkably improved lithium storage performance including high rate capacity and long cycle life, which deliver a discharge capacity of 662 mA h g-1 for 150 cycles at 0.5 C, corresponding to an elevated capacity retention of 90.7%. The improved electrochemical performances can be assigned to the generation of stable solid electrolyte interface films and suppression of the shuttle behavior with the protection of the MnO2 coating layer on Ni3S2 nanorod arrays.

Pharmacological potential of the combination of Salvia miltiorrhiza (Danshen) and Carthamus tinctorius (Honghua) for diabetes mellitus and its cardiovascular complications.

Metabolic syndrome, such as diabetes mellitus, obesity, atherosclerosis, and high blood pressure (HBP), are closely linked pathophysiologically. However, current monotherapies for metabolic syndrome fail to target the multifactorial pathology via multiple mechanisms, as well as resolving the dysfunctionality of the cells and organs of the body. We aimed to provide a comprehensive and up-to-date review of the pharmacological advances, therapeutic potential, and phytochemistry of Salvia miltiorrhiza, Carthamus tinctorius, and Danhong injection (DHI). We discussed the molecular mechanisms of the bioactive constituents relating to diabetes mellitus and metabolic disease for further research and drug development. Interestingly, Salvia miltiorrhiza, Carthamus tinctorius, and DHI have anti-inflammatory, anti-glycemic, anti-thrombotic, and anti-cancer properties; and they mainly act by targeting the dysfunctional vasculatures including the inflammatory components of the disease to provide vascular repair as well as resolving oxidative stress. The major bioactive chemical constituents of these plants include polyphenolic acids, diterpene compounds, carthamin, and hydroxysafflor yellow A. Treatment of diabetes mellitus and its associated cardiovascular complication requires a comprehensive approach involving the use of appropriate traditional Chinese medicine formula. Danshen, Honghua, and DHI target the multiple risk factors regulating the physiologic function of the body and restore normalcy, apart from the traditional advice on exercise and diet control as treatment options in a metabolic syndrome patient.

Identification of key pathways and differentially expressed genes in bronchopulmonary dysplasia using bioinformatics analysis.

OBJECTIVES: The objective of this study was to discover unknown differentially expressed genes (DEGs) associated with bronchopulmonary dysplasia (BPD), analyze their functions and enriched signaling pathways, and identify hub genes correlating with BPD incidence and evolvement. RESULTS: Of 1289 DEGs identified, 568 were downregulated and 721 were upregulated. The DEGs were mainly associated with oxidative stress, angiogenesis, extracellular matrix, inflammation, cell cycle, and protein binding. Eight DEGs were identified as hub genes, including C-X-C motif chemokine ligand 5 (Cxcl5), connective tissue growth factor (Ctgf), interleukin 6 (IL6), matrix metallopeptidase 9 (Mmp9), mitogen-activated protein kinase 14 (Mapk14), platelet and endothelial cell adhesion molecule 1 (Pecam1), TIMP metallopeptidase inhibitor 1 (Timp1), and TIMP metallopeptidase inhibitor 2 (Timp2). IL6 mRNA and protein expression levels were significantly increased in the peripheral blood of neonates with BPD. CONCLUSIONS: Hence, BPD involves complex biological changes. Our findings indicate that inflammation and angiogenesis may play major roles in BPD pathogenesis and that IL6 has the potential to serve as a biomarker for early BPD diagnosis.

Preparation and Characterization of PLGA-PEG-PLGA Nanoparticles Containing Salidroside and Tamoxifen for Breast Cancer Therapy.

Nanoparticles (NPs) containing the hydrophilic drug salidroside (Sal) and the hydrophobic drug tamoxifen (Tam) were prepared using a triblock copolymer poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA to achieve synergism in the treatment of breast cancer. The double emulsion (w/o/w) method was used to prepare Sal-Tam NPs with an average particle size of 275.3 ± 44.0 nm, a polydispersity index of 0.302 ± 0.102, and a zeta potential of - 6.98 ± 2.99. The entrapment efficiency of the hydrophilic and hydrophobic components was 32.63% ± 0.73% and 49.18% ± 3.04%, respectively. On differential scanning calorimetry, the NPs showed the amorphous nature of both Sal and Tam. The sustained release of Sal and Tam from the NPs was significantly prolonged under physiological conditions (pH 7.4). The CCK-8 assay using the 4T1 cell line revealed a 1.7-fold decrease in the IC50 value for Sal-Tam NPs when compared with free Tam. The in vivo anti-tumor effect was assessed in BALB/c mice, and the results demonstrated that these NPs decreased the tumor volume compared with saline and showed high anti-tumor activity. A pharmacokinetic study showed significant enhancement of the bioavailability of Tam in Sal-Tam NPs compared with free Tam in suspension. The intracellular and mitochondrial anti-oxidative effect of Sal was thought to be attributed to the promising anti-tumor effect of drug co-delivery. This study confirmed that the use of Sal-Tam NPs may be a promising approach in breast cancer therapy.

Proteomic Analysis Reveals that Odoroside A Triggers G2/M Arrest and Apoptosis in Colorectal Carcinoma Through ROS-p53 Pathway.

Odoroside A (OA) is an active ingredient extracted from the leaves of Nerium oleander Linn. (Apocynaceae). This study aims to examine the anticancer bioactivity of OA against CRC cells and to investigate the action mechanisms involved. As a result, OA can significantly inhibit cellular ability and induce apoptosis of CRC cells in a concentration-dependent manner without any obvious cytotoxicity in normal colorectal epithelial cells. Then, quantitative proteomics combined with bioinformatics is adopted to investigate the alterations of proteins and signaling pathways in response to OA treatment. As suggested by the proteomic analysis, flow cytometry and Western blotting analyses validate that exposure of CRC cells to OA causes cell cycle arrest and apoptosis, accompanied with the activation of the ROS/p53 signaling pathway. This observation demonstrates that OA, as a natural product, can induce oxidative stress to suppress tumor cell growth, implicating a novel therapeutic agent against CRC without obvious side effects.

Isopsoralen induces different subchronic toxicities and metabolomic outcomes between male and female Wistar rats.

Isopsoralen is a major active and quality-control component of Fructus Psoraleae, but lacks a full safety evaluation. We evaluated the oral toxicity of isopsoralen in Wistar rats treated for 3 months at doses of 0, 3.5, 7.0, and 14 mg/kg. Additionally, the plasma metabolomics of isopsoralen in male and female rats treated for 3 months at doses of 0 and 14 mg/kg were investigated by gas chromatography-mass spectrometry. Many abnormalities were observed in the isopsoralen-treated rats, including suppression of body weight gain, and changes in serum biochemical parameters and visceral coefficients. Histopathological changes in liver, pancreatic, and reproductive system tissues were also observed in the isopsoralen-treated rats. The metabolomic analyses showed alterations in many metabolites (19 in female rats; 28 in male rats) after isopsoralen administration. The significant changes in these metabolites revealed metabolomic alterations in the isopsoralen-treated rats, especially in amino acid metabolism regardless of sex, including phenylalanine, tyrosine, and tryptophan biosynthesis and glycine, serine, and threonine metabolism. Furthermore, fatty acid metabolism comprised the main affected pathways in female rats, while lipid metabolism and energy metabolism were the main affected pathways in male rats.