New insight into oxidative stress and inflammatory responses to kidney stones: Potential therapeutic strategies with natural active ingredients.

Kidney stones, a prevalent urological disorder, are closely associated with oxidative stress (OS) and the inflammatory response. Recent research in the field of kidney stone treatment has indicated the potential of natural active ingredients to modulate OS targets and the inflammatory response in kidney stones. Oxidative stress can occur through various pathways, increasing the risk of stone formation, while the inflammatory response generated during kidney stone formation further exacerbates OS, forming a detrimental cycle. Both antioxidant systems related to OS and inflammatory mediators associated with inflammation play roles in the pathogenesis of kidney stones. Natural active ingredients, abundant in resources and possessing antioxidative and anti-inflammatory properties, have the ability to decrease the risk of stone formation and improve prognosis by reducing OS and suppressing pro-inflammatory cytokine expression or pathways. Currently, numerous developed natural active ingredients have been clinically applied and demonstrated satisfactory therapeutic efficacy. This review aims to provide novel insights into OS and inflammation targets in kidney stones as well as summarize research progress on potential therapeutic strategies involving natural active ingredients. Future studies should delve deeper into exploring efficacy and mechanisms of action of diverse natural active ingredients, proposing innovative treatment strategies for kidney stones, and continuously uncovering their potential applications.

Improvement effect of compound Ento-PB on oxazolone-induced ulcerative colitis in rats.

PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.

Chromosome-level genome assembly of the medicinal insect Blaps rhynchopetera using Nanopore and Hi-C technologies.

The Blaps rhynchopetera Fairmaire is a significant medicinal resource in southwestern China. We utilized Nanopore and Hi-C technologies in combination to generate a high-quality, chromosome-level assembly of the B. rhynchopetera genome and described its genetic features. Genome surveys revealed that B. rhynchopetera is a highly heterozygous species. The assembled genome was 379.24 Mb in size, of which 96.03% was assigned to 20 pseudochromosomes. A total of 212.93 Mb of repeat sequences were annotated and 26,824 protein-coding genes and 837 non-coding RNAs were identified. Phylogenetic analysis indicated that the divergence of the ancestors of B. rhynchopetera and its closely related species Tenebrio molitor at about 85.6 mya. The co-linearity analysis showed that some chromosomes of B. rhynchopetera may have happen fission events and it has a good synteny relationship with Tribolium castaneum. Furthermore, in the enrichment analyses, the gene families related to detoxification and immunity of B. rhynchopetera facilitated the understanding its environmental adaptations, which will serve as a valuable research resource for pest control strategies and conservation efforts of beneficial insects. This high-quality reference genome will also contribute to the conservation of insect species diversity and genetic resources.

Shotgun metagenomics reveals the gut microbial diversity and functions in Vespa mandarinia (Hymenoptera: Vespidae) at multiple life stages.

Wasps play important roles as predators and pollinators in the ecosystem. The Jingpo minority residing in Yunnan Province, China, has a traditional practice of using wine infused with mature wasps as a customary remedy for managing rheumatoid arthritis. The larva of the wasp is also a tasteful folk dish that has created a tremendous market. There is a paucity of survival knowledge, which has greatly restricted their potential applications in food and healthcare. Recent research has highlighted the importance of gut microbiota in insect growth. Nevertheless, there is still a lack of understanding regarding the composition, changes, and functions of the gut microbiota in Vespa mandarinia during development. In this research, the gut microbiota were investigated across three growth stages of Vespa mandarinia using a metagenomic technology. The result revealed that there are significant variations in the proportion of main gut microbes during the metamorphosis of Vespa mandarinia. Tenericutes were found to dominate during the larval stage, while Proteobacteria emerged as the dominant group post-pupation. Through a comprehensive analysis of the gut microbiota metagenome, this study revealed functional differences in the wasp gut microbiota at various growth stages. During the larval stage, the gut microbiota plays a central role in promoting metabolism. Following pupation, the gut microbiota exhibited diversified functions, likely due to the complex environments and diverse food sources encountered after metamorphosis. These functions included amino acid metabolism, compound degradation, and defense mechanisms. This research provides an extensive dataset on the gut microbiota during the metamorphosis of Vespa mandarinia, contributing to a deeper understanding of the influence of gut microbiota on wasp growth. Furthermore, this study uncovers a unique microbial treasure within insect guts, which is important for advancing the application of wasps in the fields of food and medicine.

The therapeutic effect of wasp venom (Vespa magnifica, Smith) and its effective part on rheumatoid arthritis fibroblast-like synoviocytes through modulating inflammation, redox homeostasis and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.

[Pollution Characteristics and Risk Assessment of Heavy Metals in Surface Dusts and Surrounding Green Land Soils from Yellow River Custom Tourist Line in Lanzhou].

In order to investigate the contamination levels of dust and its surrounding green land soil heavy metal pollution and potential ecological and health risks in the scenic areas of urban waterfront parks, the gardens, squares, and theme parks of the Yellow River Custom Tourist Line in Lanzhou were selected as the research area, using 27 dust samples and 26 soil samples from its surrounding green lands. The contamination characteristics and potential ecological risks of eight heavy metals (Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb) were evaluated using the geo-accumulation index (Igeo), single-factor pollution index (Pi), Nemerow integrated pollution index (PN), and improved potential ecological risk index (RI). The human health risk assessment was also evaluated using the exposure risk model. The results showed that the average concentrations of the other heavy metals in the surface dusts were higher than the background values of Gansu Province and Lanzhou City, except that the As mean concentrations in the surface dusts and the surrounding green land soils were slightly lower than the Gansu Province background values. For its surrounding green land soils, the mean concentrations of the other heavy metals (Cu, Zn, Cd, Hg, and Pb) exceeded the soil background values of Gansu Province and Lanzhou City, whereas the Cr and Ni mean concentrations were lower than their corresponding soil background values of Gansu Province and Lanzhou City. The geo-accumulation and single-factor pollution indices demonstrated that a slight to moderate pollution of Cr, Cu, Zn, Cd, Hg, and Pb occurred in surface dusts, and Cu, Zn, Cd, Hg, and Pb appeared in varying degrees of contamination levels in its surrounding green land soils. The Nemerow integrated pollution index analysis manifested that the overall contamination status of the study areas was between slightly and heavily polluted. The potential ecological risk index suggested that Cd and Hg were recognized as significant pollutant elements and that the RI of the other heavy metals were all below 40, presenting slight ecological risk. The health risk assessment indicated that ingestion was the dominant exposure pathway for heavy metals from the surface dusts and the surrounding green land soils, and no carcinogenic and noncarcinogenic risks posed threats to adults and children.

Proliferation Inhibitory Activity of Quinones from Blaps rynchopetera Defense Secretion on Colorectal Tumor Cells.

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3ß and APC, while down-regulate that of ß-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/ß-catenin pathway of HT-29 cells. CONCLUSION: Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/ß-catenin pathway-related mRNA and protein expressions.

Polyketides with antimicrobial activities from Penicillium canescens DJJ-1.

Two undescribed polyketides canecines A-B, one unreported cyclopentenone canecine C, together with 12 known compounds were isolated from an extract of the fungus Penicillium canescens DJJ-1. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with dJ-DP4 or DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Canecine A was a grisan polyketide featuring a dimethyltetrahydro-4H-furo[2,3-b]pyran. Canecine A exhibited significant inhibitory activity against Candida albicans with an MIC value of 1 µg/mL and showed inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. These results enrich the structural diversities of polyketides from endophytic fungi.

Effects of wasp venom on venous thrombosis in rats.

Objectives: This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis. Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats. Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats.

PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.