Ultrasound-triggered biomimetic ultrashort peptide nanofiber hydrogels promote bone regeneration by modulating macrophage and the osteogenic immune microenvironment.

The immune microenvironment plays a vital role in bone defect repair. To create an immune microenvironment that promotes osteogenesis, researchers are exploring ways to enhance the differentiation of M2-type macrophages. Functional peptides have been discovered to effectively improve this process, but they are limited by low efficiency and rapid degradation in vivo. To overcome these issues, peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel. These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation, activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle, inhibiting reactive oxygen species production and enhancing M2 macrophage polarization. The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I, accelerating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. Thus, modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.

Improving the physicochemical stability and release properties of curcumin using κ-carrageenan/scallop hydrolysates hydrogel beads.

Scallop (Patinopecten yessoensis) male gonad hydrolysates (SMGHs)/κ-carrageenan (KC)/KCl beads with SMGHs:KC ratios (0:10-5:5) were investigated. SMGHs/KC/KCl-Cur bead (5:5) exhibited the most intact spherical morphology and highest Cur loading content of 0.063 mg/0.1 g bead, ascribing to a shortened T23 from 1607.9 to 966.4 ms, and red and blueshifts of OH, NH, amide I and II bands. The undetected fingerprint region within 7.82°-28.90° of SMGHs/KC/KCl-Cur beads indicated successful Cur entrapment. Moreover, SMGHs/KC/KCl-Cur beads exhibited shrinkage network backbones and larger void pores as SMGHs increased, with vessel percentage area, total number of junctions, total vessel length decreasing from 52.1, 1446.8, 57931.4 to 39.7, 530.5, 34458.4, and lacunarity increasing from 0.048 to 0.111, respectively. Furthermore, Cur showed approximately 50% release contents in colon phase and above 90% retention rate during 30 days of storage at 4 °C. These results suggested that SMGHs/KC/KCl-Cur beads exhibited sustained-release of Cur and promised stable Cur preservation.

Huanglian Ganjiang decoction alleviates ulcerative colitis by restoring gut barrier via APOC1-JNK/P38 MAPK signal pathway based on proteomic analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a kind of chronic intestinal inflammation accompanied with abdominal pain, diarrhea and hematochezia. Huanglian Ganjiang decoction (HGD) derived from "Beiji Qianjin Yao Fang" was used for UC patients clinically. However, the specific mechanism of HGD in treating UC remain unclear. AIM OF STUDY: Our study devoted to demonstrating the therapeutic effect of HGD for colitis and clarifying the underlying mechanism. MATERIALS AND METHODS: UPLC-MS was carried out to identify the ingredients of HGD. UC mice were induced by giving 3% dextran sulfate sodium (DSS) solution for one week and treated by HGD for another week. Body weight fluctuation, disease activity index (DAI), colon length and pathological change of colon tissues were observed to evaluate therapeutical effect of HGD. ELISA and qPCR were carried out to estimate the inflammatory state. Western blot, qPCR and immunofluorescence were used to access the expression of tight junction proteins. Tandem mass tag (TMT)-Based proteomics and network pharmacology was launched to screen and predict the potential targets and pathway regulated by HGD. RESULTS: Based on the UPLC-MS/MS analysis, 100 components were identified in HGD. After 7-day treatment, HGD significantly alleviated colitis-associated symptoms including body weight loss, shorted colon, increase of DAI score, histopathologic lesions. HGD also reduced inflammatory cytokines IL-6 and IL-1ß levels, increased the number of goblet cells and restored tight junction proteins Occludin, Claudin-1 in colon. Network pharmacology study predicted that tight junction and MAPK pathway might be affected by HGD in colitis mice. APOC1 was screened out as key target in HGD-treated mice using TMT-based proteomics study. Further Western blot results showed that HGD reduced expressions of APOC1, p-P38 and p-JNK. CONCLUSION: HGD improves general symptoms of colitis mice at medium and high doses, which may be associated with restoring tight junction and intestinal barrier integrity and function through suppression of APOC1-JNK/P38 MAPK signal pathway.

Insights into effects of grain boundary engineering in composite metal oxide catalysts for improving catalytic performance.

Volatile Organic Compounds (VOCs) have long been a threat to human health. However, designing economical and efficient transition metal composite oxide catalysts for VOCs purification remains a challenge. Herein, this study demonstrates the enormous potential of grain boundary engineering in facilitating VOCs decomposition over ordered mesoporous composite oxide denoted as 3D-MnxCoy (x, y = 1, 3, 5, 7, 9). Specifically, the three-dimensional (3D) Mn7Co1 catalyst shows 100% ethyl acetate removal efficiency for a continuous airflow containing 1000 ppm ethyl acetate over 60000 h-1 space velocity at 160 °C. Mechanism study suggests that the high catalytic performance originates from the lattice distortion caused by the introduction of heteroatoms, along with the size effect of nanopore walls, which leads to the formation of various grain boundaries on the catalyst surface. The presence of grain boundaries facilitates the generation of oxygen vacancies, thus promoting the migration and activation of oxygen species. Furthermore, the near-atmospheric pressure X-ray photoelectron spectroscopy (NAP- XPS) monitoring results reveal that the bimetallic synergy enhanced by grain boundary accelerates the catalytic reaction rate of VOCs through Mn3++Co3+↔Mn4++Co2+ redox cycle. This study may shed light on the great potential of ordered mesoporous bimetallic oxide catalysts in VOCs pollution control.

Integrated proteomics and metabolomics reveals metabolism disorders in the α-syn mice and potential therapeutic effect of Acanthopanax senticosus extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr.et.Maxim.)Harms(AS) is an extract of Eleutherococcus senticocus Maxim(Rupr.et.Maxim.). In modern medical interpretation, Acanthopanax senticosus can be used to treat Parkinson's disease, and a large number of modern pharmacological and clinical studies also support this application. Our study demonstrated that AS extracts can increase the activity of various antioxidant enzymes and improve the symptoms of Parkinson's disease in mice. AIM OF THE STUDY: The current study looked at the protective effect of Acanthopanax senticosus extracts(ASE) in preventing PD. METHODS AND MATERIALS: First, the α-syn-overexpressing mice were chosen as suitable models for Parkinson's disease in vivo. HE staining was used to observe the pathological changes in the substantia nigra. Meanwhile, TH expression in substantia nigra was analyzed by immunohistochemistry. Behavioral and biochemical tests evaluated neuroprotective effects of ASE on PD mice. Subsequently, combined with proteomics and metabolomics analysis, the changes in brain proteins and metabolites in mice treated with ASE for PD were studied. Finally, Western blot was used to detect metabolome-related and proteomic proteins in the brain tissue of α-syn mice. RESULTS: Forty-nine common differentially expressed proteins were screened by proteomics analysis, among which 28 were significantly up-regulated,and 21 were significantly down-regulated. Metabolomics analysis showed that twenty-five potentially important metabolites were involved in the therapeutic effect of ASE on PD. Most of the different proteins and metabolites were considered to be enriched in a variety of species in metabolic pathways, including glutathione metabolism and alanine aspartate and glutamate metabolism and other pathways, which means that ASE may have molecular mechanisms to ameliorate PD dysfunction. In addition, we found that decreases in glutathione and glutathione disulfide levels may play a critical role in these systemic changes and warrant further investigation. In the glutathione metabolic pathway, ASE also acts on GPX4, GCLC and GCLM. CONCLUSIONS: ASE can effectively relieve behavioral symptoms of α-syn mice and relieve oxidative stress in brain tissue. These findings suggest that ASE offers a potential solution to target these pathways for the treatment of PD.

Sequential starch modification by branching enzyme and 4-α-glucanotransferase improves retention of curcumin in starch-alginate beads.

A new super-branched amylopectin with longer exterior chains was produced from normal maize starch by modification with branching enzyme followed by 4-α-glucanotransferase, and applied for co-entrapment of a curcumin-loaded emulsion in alginate beads. The network structure of the gel beads was obtained with Ca2+-cross-linked alginate and a modest load of retrograded starch. The dual enzyme modified starch contained more and longer α-1,6-linked branch chains than single enzyme modified and unmodified starches and showed superior resistance to digestive enzymes. Alginate beads with or without starch were of similar size (1.69-1.74 mm), but curcumin retention was improved 1.4-2.8-fold in the presence of different starches. Thus, subjecting the curcumin-loaded beads to in vitro simulated gastrointestinal digestion resulted in retention of 70, 43 and 22 % of the curcumin entrapped in the presence of modified, unmodified, or no starch, respectively. Molecular docking provided support for curcumin interacting with starch via hydrogen bonding, hydrophobic contacts and π-π stacking. The study highlights the potential of utilizing low concentration of dual-enzyme modified starch with alginate to create a versatile vehicle for controlled release and targeted delivery of bioactive compounds.

Efficacy and mechanism study of Baichanting compound, a combination of Acanthopanax senticosus (Rupr. and Maxim.) Harms, Paeonia lactiflora Pall and Uncaria rhynchophylla (Miq.) Miq. ex Havil, on Parkinson's disease based on metagenomics and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a rapidly progressing neurological disorder. Currently, Medication for PD has numerous limitations. Baichanting Compound (BCT) is a Chinese herbal prescription, a Combination of Acanthopanax senticosus (Rupr. and Maxim.) Harms, Paeonia lactiflora Pall and Uncaria rhynchophylla (Miq.) Miq. ex Havil, that was developed to treat PD and holds a national patent (ZL, 201110260536.3). AIM OF THE STUDY: To clarify the therapeutic effect of BCT on PD and explore its possible mechanism based on metabolomics and metagenomics. MATERIALS AND METHODS: C57BL/6 mice were used as a control group, and α-syn transgenic C57BL/6 mice were randomly assigned to the PD (without treatment) or BCT (with BCT treatment) group. UPLC-MS was performed to detect dopamine levels in brain tissue, while ELISA was used to determine inflammatory factors such as IL-1ß, IL-6, TNF-α, IFN-γ and NO, and oxidative stress indicators such as malondialdehyde, superoxide dismutase and glutathione peroxidase enzyme activity. Fecal metabolomics was used to detect fecal metabolic profiles, screen differential metabolic markers, and predict metabolic pathways by KEGG enrichment analysis. Metagenomics was used to determine the intestinal microbial composition, and KO enrichment analysis was performed to predict the potential function of different gut microbiota. Finally, Spearman correlation analysis was used to find the possible relationships among intestinal flora, metabolic markers, inflammatory factors, oxidative stress and dopamine levels. RESULTS: BCT increased the superoxide dismutase activity of α-Syn transgenic C57BL/6 mice (P < 0.01), decreased the levels of TNF-α, IFN-γ, IL-1ß, IL-6, NO and malondialdehyde (P < 0.01, 0.05), and increased the release of dopamine (P < 0.01). Metabolomics results show that BCT could regulate Acetatifactor, Marvinbryantia, Faecalitalea, Anaeromassilibacillus, Anaerobium, Pseudobutyrivibrio and Lachnotalea and Acetatifactor_muris, Marvinbryantia_formatexigens, Lachnotalea_sp_AF33_28, Faecalitalea_sp_Marseille_P3755 and Anaerobium_acetethylicum, Gemmiger_sp_An120 abundance to restore intestinal flora function, and reverse fecal metabolism trend, restoring the content of α-D-glucose, cytidine, L-glutamate, L-glutamine, N-acetyl-L-glutamate, raffinose and uracil. In addition, it regulates arginine biosynthesis, D-glutamine and D-glutamate, pyrimidine, galactose and alanine, aspartate and glutamate metabolic pathways. CONCLUSION: BCT may regulate the composition of the gut microbiota to reverse fecal metabolism in PD mice to protect the substantia nigra and striatum from oxidative stress and inflammatory factors and ultimately play an anti-PD role.

In vivo imaging of the neuronal response to spinal cord injury: a narrative review.

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury (SCI). However, this subject has been neglected in part because appropriate tools are lacking. Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease. This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques, and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI. We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations. Finally, we identify the challenges and possible solutions for spinal cord neuron imaging.

Association between changes in potentially inappropriate medication use and adverse outcomes during hospitalization in older adults: A retrospective study.

PURPOSE: To evaluate the association between the change in the number of PIMs in older adults during hospitalization and adverse outcomes. METHODS: This retrospective cohort study was conducted in the internal medicine wards of a tertiary teaching hospital between May and December 2017. 3,460 patients (77.5±8.4 years, 60.4% male) were enrolled, and 206 patients died during hospitalization. PIMs were defined using the Beers Criteria as suggested by the American Geriatrics Society. Adverse outcomes studied were functional decline (a loss in 1 or more activities of daily living from admission to discharge), prolonged length of stay (LOS) (≥14 days), and mortality. RESULTS: 2258 patients (65.3%) had increasing PIMs during hospitalization. They tended to be younger (77.0±8.3 versus 78.5±8.5 years, p<0.001) and had lower numbers of PIMs at admission (0.4±0.8 versus 0.8±1.1, p<0.001). Increasing PIM use was strongly associated with greater functional decline (aOR 1.36, 95%CI 1.01-1.67, p=0.005), prolonged LOS (aOR 3.47, 95%CI 2.71-4.44, p<0.001) and higher mortality rate (aOR 2.68, 95%CI 1.75-4.12, p<0.001), even after adjusting for all covariates. We observed a strong association between adverse outcomes and increasing PIMs in older adults during hospitalization (p for trend <0.001). CONCLUSIONS: Older adults with increasing PIMs during hospitalization were at greater risk for functional decline, prolonged LOS, and mortality, especially in those with three or more PIMs. Further studies are needed to better understand the complex interactions and to evaluate the effectiveness of intervention programs to lower PIM number and improve discharge outcomes for patients who had increasing PIM use during hospitalization.

Polystyrene nanoparticle exposure accelerates ovarian cancer development in mice by altering the tumor microenvironment.

Microplastics and nanoplastics are ubiquitous pollutants, widely spread in the living and natural environment. Although their potential impact on human health has been investigated, many doubts remain about their effects in carcinogenic processes. We investigated the potential effects and its molecular mechanisms of polystyrene nanoplastics (PS-NPs) on epithelial ovarian cancer (EOC) using the human EOC cell line HEY as an in vitro cell model and mice as a mammalian model. In vivo exposure to PS-NPs (100 nm; 10 mg/L) via drinking water significantly accelerated EOC tumor growth in mice. In in vitro tests the PS-NPs reduced the relative viability of EOC cells in a dose-dependent manner. Histological analysis showed increased mitotic counts in EOC tumor tissues of PS-NP exposed mice. PS-NP exposure significantly affected gene expression and disturbed many metabolic pathways in both cultured EOC cells and EOC tumor tissue in mice. Gene functional and pathway analysis indicated that immune-related responses and the tumor microenvironment pathway were significantly enriched, which may be attributed to disturbed expression of thrombomodulin (THBD) and its regulators. It may be concluded that PS-NP exposure caused a significant acceleration of EOC tumor growth in mice and a dose-dependent decrease in the relative viability of EOC cells by altering the tumor growth microenvironment. This offers new insights into the mechanisms underlying PS-NP effects on EOC.

Effects of sub-chronic exposure to microcystin-LR on the endocrine system of male rats.

Microcystins (MCs) can cause reproductive and developmental toxicity and disrupt endocrine homeostasis in mammals. In the present study, male, Sprague-Dawley (SD) rats were administrated 3 or 30 µg MC-LR/kg, body mass (bm) per day via intraperitoneal (i.p.) injections for 6 weeks. Effects of MC-LR on histology, hormone concentrations, gene transcriptional profiles and protein expressions along the hypothalamic-pituitary-adrenal (HPA), -gonad (HPG) and -thyroid (HPT) axes were assessed. Sub-chronic administration with MC-LR caused histological damage to hypothalamus, pituitary, adrenal, testes and thyroid and affected relative masses of pituitary, adrenal and testes. The HPA axis was activated and serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were significantly augmented. Along the HPG axis, serum concentrations of gonadotropin-releasing hormone (GnRH) and dihydrotestosterone (DHT) were diminished, while concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) were augmented. For the HPT axis, only concentrations of free tetra-iodothyronine (fT4) were significantly diminished, while concentrations of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH) or free tri-iodothyronine (fT3) were not significantly changed. Also, several genes and proteins related to synthesis of steroid hormones were significantly altered. Findings of the present study illustrate that MC-LR can cause endocrine-disrupting effects through the disruption of synthesis and secretion of hormones along the HPA, HPG and HPT axes and negative feedback regulation. Also, there could be crosstalk among HPA, HPG and HPT axes. These findings elucidate mechanisms of endocrine-disrupting effects of MCs.

Migration of nanocolloid-carrying antibiotics in paddy red soil during the organic fertilization process.

Soil nanocolloids are highly mobile and can act as carriers for the transport of antibiotics to a wider and deeper range of soils; however, the inherent behavior and mechanism of nanocolloid-carrying antibiotics in soil remain unclear. In this study, we conducted a comprehensive investigation of the migration of antibiotics in paddy red soil during the organic fertilization process using four common soil nanocolloids: kaolin (KL), montmorillonite (MT), hematite (HT), and humic acid (HA). The results showed that nanocolloid carriers promoted the intra-medium (from soil surface to the bottom) and inter-medium transfer (from organic fertilizers to soil) of antibiotics. The migration mechanisms of antibiotics carried by the nanocolloids differed: the phenolic hydroxyl and carboxyl groups of HA esterified with the carboxyl groups of quinolones and phenolic hydroxyl groups of tetracyclines, respectively, while the oxygen atoms of HT formed stabilizing complexes with the soil, which could further adsorb antibiotics using their functional group-rich complexes. Smaller antibiotic compounds were adsorbed in the metal oxide interlayer of MT via cation exchange, whereas KL adsorbed antibiotics on its metal oxide surface layer in the same way but were susceptible to desorption. Additionally, nanocolloids changed the adsorption capacity of soil for antibiotics and influenced the enrichment of dominant/functional bacteria (e.g., Burkholderiaceae) and thus varied the vertical distribution of antibiotics in soil. These findings enhance our understanding of the migration behavior and mechanism of nanocolloid-carrying antibiotics in red paddy soil and provide a theoretical foundation for preventing and controlling antibiotic pollution in arable systems.

Changes of atrazine dissipation and microbial community under coexistence of graphene oxide in river water.

The coexistence of herbicide atrazine (ATZ) and the nanomaterial graphene oxide (GO) in natural water bodies will be an inevitable scenario due to their widespread application and consequent release into aquatic ecosystems. But the dissipation of ATZ with GO and the response of the microbial community to their combination are still not clear. Here, we investigated the dissipation dynamics and transformation of ATZ with and without GO in river water after 21-d incubation. In the presence of GO, ATZ residue significantly decreased by 11%-43%; the transformation of ATZ markedly increased by 11%-17% when ATZ concentrations were not above 1.0 mg∙L-1. The direct adsorption of ATZ on GO, mainly via π-π interactions, proton transfer and hydrogen bonding, contributed 54%-68% of the total increased ATZ dissipation by GO. ATZ and ATZ+GO exerted effects of similar magnitude on microbial OTU numbers with an increase of bacterial diversity. The coexisting GO increased the relative abundance of ATZ-degradation bacteria and Chitinophagales, thus improving ATZ transformation. This work indicated that the coexistence of GO at environmentally relevant concentrations can effectively reduce ATZ residues and promote the transformation of ATZ to degradation products in river water; nevertheless, the potential risk of GO acting as an ATZ carrier should be given more prominence.

Panax notoginseng saponin alleviates pulmonary fibrosis in rats by modulating the renin-angiotensin system.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have shown potential in the treatment of PF. Panax notoginseng saponin (PNS) is extracted from the widely used traditional Chinese medicinal herb Panax notoginseng (Burkill) F. H. Chen, exhibiting therapeutic effects in pulmonary diseases treatment. AIM OF THE STUDY: This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats. MATERIALS AND METHODS: PF was induced in rats by intratracheal administration of bleomycin (BLM, 5 mg/kg). After disease model induction, the rats were treated with PNS (50, 100, or 200 mg/kg per day) or pirfenidone (PFD, 50 mg/kg per day) for 28 days. Lung function, histopathological changes, collagen deposition, and E- and N-cadherin levels in lung tissue were evaluated. The mechanism of action of PNS was investigated using tandem mass tag-based quantitative proteomics analysis. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were performed to verify the proteomic results. RESULTS: PNS treatment improved lung function, ameliorated the BLM-induced increase in the lung coefficient, attenuated the degree of alveolar inflammation and fibrosis, and reduced the elevated collagen level in PF rats. PNS treatment also down-regulated the expression of N-cadherin while up-regulating the expression of E-cadherin. Proteomic and bioinformatic analyses revealed that the renin-angiotensin system (RAS) was closely related to the therapeutic effect of PNS. Immunohistochemistry, Western blot, and ELISA results indicated that PNS exerted its anti-fibrotic effect via regulation of the balance between the angiotensin-converting enzyme (ACE)-angiotensin (Ang)II-AngII receptor type 1 (AT1R) and ACE2-Ang(1-7)-MasR axes. CONCLUSIONS: PNS ameliorates BLM-induced PF in rats by modulating the RAS homeostasis, and is a new potential therapeutic agent for PF.

Huayuwendan decoction ameliorates inflammation via IL-17/NF-κB signaling pathway in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huayuwendan decoction (HYWD) is a broad used traditional Chinese medicine and therapeutic effects against type 2 diabetes mellitus (T2DM). The mechanism of HYWD on the treatment of T2DM is still unclear. AIM OF THE STUDY: For this reason, this study was performed to uncover the effects and mechanism of action of HYWD on T2DM. MATERIALS AND METHODS: Male Wistar rats were chosen to set up the T2DM model. This study was randomly divided into six groups: CON (control), MOD (model), HYWDL (Huayuwendan decoction Low Dose), HYWDM (Huayuwendan decoction Middle Dose), HYWDH (Huayuwendan decoction High Dose), and MET (Metformin). Body weight gains were estimated. Using H&E staining, pathological alterations was explored. The serums of fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2 h PG) were detected by Roche blood glucose meter. LDL-C and HDL-C were analyzed by automatic biochemical analyzer. Network pharmacology analyzed the active ingredients, drug targets, and key pathways of HYWD in T2DM treatment. The islet function and inflammation related factors were determined by ELISA. NF-κB signaling pathway or IL-17 signaling pathway related proteins were analyzed by Western blotting. IL-17RA were determined by immunohistochemistry analyze. RESULTS: HYWD inhibited weight gain in T2DM rats. Histopathological results showed that HYWD inhibits liver injury. HYWD suppressed LDL-C and enhanced HDL-C in serum of T2DM rats. HYWD reduce FPG and 2 h PG, inhibit Fins, GSP and IRI, but enhance IAI in serum of T2DM rats. In addition, the network pharmacology results identified 292 chemical compounds in HYWD. 279 candidate targets were recognized, including IL-17A, IL-1ß, NFкB, stats, mmp3, and cxcl2. The pathways revealed that the possible target of HYWD related with the regulation of IL-17 signaling pathway and NF-κB pathway. Then in vivo study, HYWD reduced the levels of IL-6, TNF-α, IL-17 and IL-1ß in serum and inhibit the protein expression involved in IL-17/NF-κB signaling pathway. CONCLUSIONS: The study demonstrates that HYWD may improve T2DM by repressing with the IL-17/NF-κB signaling pathway, which offer encouraging support for using alternative medicine of type 2 diabetes mellitus.

Research progress on traditional Chinese medicine-induced apoptosis signaling pathways in ovarian cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: As a "silent killer" that threatens women's lives and health, ovarian cancer (OC) has the clinical characteristics of being difficult to detect, difficult to treat, and high recurrence. Traditional Chinese medicine (TCM) can be utilized as a long-term complementary and alternative therapy since it has shown benefits in alleviating clinical symptoms of OC, decreasing toxic side effects of radiation and chemotherapy, as well as enhancing patients' quality of life. AIM OF THE REVIEW: This paper reviews how TCM contributes to the apoptosis of OC cells through signaling pathways, including active constituents, extracts, and herbal formulas, with the aim of providing a basis for the development and clinical application of therapeutic strategies for TCM in OC. METHODS: The search was conducted from scientific databases PubMed, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed databases aiming to elucidate the apoptosis signaling pathways in OC cells by TCM. The articles were searched by the keywords "ovarian cancer", "apoptosis", "signaling pathway", "traditional Chinese medicine", "Chinese herbal monomer", "Chinese herbal extract", and "herbal formula". The search was conducted from January 2013 to June 2023. A total of 97 potentially relevant articles were included, including 93 articles on Chinese medicine active constituents or extracts and 4 articles on Chinese herbal compound prescriptions. RESULTS: TCM can induce apoptosis in OC cells by regulating signaling pathways with obvious advantages, including STAT3, PI3K/AKT, Wnt/ß-catenin, MAPK, NF-κB, Nrf2, HIF-1α, Fas/Fas L signaling pathway, etc. CONCLUSION: Chinese medicine can induce apoptosis in OC cells through multiple pathways, targets, and routes. TCM has special advantages for treating OC, providing more reasonable evidence for the research and development of new apoptosis inducers.

The mechanism of microbial community succession and microbial co-occurrence network in soil with compost application.

The application of organic and chemical fertilizer into soil can regulate microbial communities. However, the response mechanism of microbial communities in soil to compost and chemical fertilizer application remain unclear. In this study, compost made of tobacco leaves individually and combined with chemical fertilizer was applied, respectively, to investigate their effect on soil microorganisms during the pot-culture process. High-throughput sequence, neutral community model and null model were employed to clarify how soil microbial community respond to the application of compost and chemical fertilizer. Furthermore, random forest model was applied to predict the relationships between the plant agronomical traits and the soil microorganism during the pot-culture process. The results demonstrated that the simultaneous application of compost and chemical fertilizer increased significantly the richness and diversity of the microorganisms in soil (p < 0.05), groups C and D led to a significant reduction in the number of nodes and edges in the microbial network (77.78 %-96.57 %). The dominant bacteria in the application of 50 g fertilizer accounted for the highest proportion (40 %) and organic matter was the main factors driving the change in bacterial communities. Compared to the tilled soil, the microbial communities of the soil with the simultaneous application of compost and chemical fertilizer were more susceptible to stochastic processes, and soil microorganisms had less influence on the growth of crops during pot-culture. In conclusion, the simultaneous application of compost and fertilizer altered the ecological functions of soil microbial communities, leading to an enhanced stochastic process of community formation.

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination.

Tetrabromobisphenol A (TBBPA) and its derivatives widely exist in various environments and biota. Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer (EC), the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear. The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC, and the crucial mechanism on the progression of EC caused by bromine flame retardants exposure. In this research, TBBPA and two of the most common TBBPA derivatives including TBBPA bis (2-hydroxyethyl ether) (TBBPA-BHEE) and TBBPA bis (dibromopropyl ether) (TBBPA-BDBPE) were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model. Under environmental concentrations, TBBPA promoted the proliferation of EC, the main derivatives of TBBPA (TBBPA-BHEE and TBBPA-BDBPE) did not present the similar facilitation effects. The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation, which resulted in the increase of downstream cell cycle and decrease of apoptosis. The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome. This finding revealed the effects of TBBPA and its derivatives on EC proliferation, thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

Radix Saposhnikoviae enhancing Huangqi Chifeng Decoction improves lipid metabolism in AS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Chifeng decoction (HQCF) combined with parsnips is a classic Chinese traditional medicine formula that has certain advantages in the clinical treatment of cardiovascular and cerebrovascular diseases. At present, there is an absence of research on the regulatory effect and mechanism of this formula on atherosclerosis (AS). The synergistic effect of Radix Saposhnikoviae (RS) in HQCF is also unclear. AIM OF THE STUDY: This study was designed to investigate the role of RS, which is designed as a guide drug for HQCF, in improving the lipid metabolism of AS. MATERIALS AND METHODS: In this study, we studied the effect of HQCF on ApoE-/- mice before and after RS compatibility. Hematoxylin and eosin (HE) staining and oil red staining were used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adenosine monophosphate-activated protein kinase (AMPK) and pAMPK in the aorta was measured by immunofluorescence, and AMPK and sterol regulatory element binding protein-1 (SREBP-1),fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in liver tissue were measured by Western blot analysis. Metabolomics was used to compare the changes in serum and liver metabolites of ApoE-/- mice before and after RS combination. RESULTS: Compared with the control group, the serum lipid levels of ApoE-/- mice increased, the aortic intima thickened with plaque formation, and liver tissue pathological changes and lipid deposition occurred. Both (HQCFT without RS)HQCS and HQCF can improve the pathological condition of tissue and regulate the blood lipid level. It was noted that HQCF could promote the phosphorylation of AMPK to activate it, inhibit the expression of SREBP-1c and FAS, reduce lipid synthesis, and inhibit ACC to promote the oxidative decomposition of fatty acids. Serum and liver metabolome results showed that HQCS and HQCF treated AS mainly by regulating glycerophospholipid metabolism, sphingolipid metabolism and the arachidonic acid metabolism pathway. Importantly, HQCF showed better efficacy in regulating lipid metabolism than the HQCS group. CONCLUSION: HQCF decoction reduces atherosclerotic lesions in the aorta and lipid accumulation in the liver, which may regulate lipid transport and metabolic function by activating the AMPK pathway. These effects can be attributed to the guidance and synergism of RS.

Colloid-bound radicals formed in NOM-enhanced Fe(III)/peroxymonosulfate process accelerate the degradation of trace organic contaminants in water.

The omnipresence of natural organic matter (NOM) in water bodies traditionally hinders the degradation of trace organic contaminants (TrOCs) in peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs). This study elucidates the positive role of NOM in enhancing the degradation of TrOCs through the Fe(III)/PMS process. During this process, NOM reduces Fe(III), yielding semiquinone-like radical (NOM•) and concurrently forming NOM-Fe(III) colloids. In addition to the Fe(II)-mediated activation pathway, Fe(III) sites on NOM-Fe(III) colloids effectively transfer electrons from NOM• or some redox-active moieties to PMS, resulting in the generation of long-lived colloid-bound SO4•-, which can readily undergo hydrolysis to produce HO•. The stabilization of SO4•- and HO• by NOM-Fe(III) colloids, combined with their moderate adsorption of TrOCs, results in surface-confined reactions that significantly enhance TrOC removal, despite the presence of concurrent quenching reactions between radicals and NOM. Further, the significant positive correlation between the phenolic contents of eight NOM types and TrOC degradation kinetics suggests phenolic moieties as the primary electron source for PMS activation. By in-situ utilizing NOM in raw water, a PMS-amended iron coagulation process with 0.2 mM Fe(III) and PMS effectively removes 90-100 % of six coexisting TrOCs. This study unveils the previously unrecognized role of colloid-bound radicals in decontamination processes, offering valuable insights into harnessing NOM's influence in advanced oxidation water treatment processes.