Comparative analysis of phytochemical profile and antioxidant and anti-inflammatory activity of four Gentiana species from the Qinghai-Tibet Plateau.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana species, known as the traditional Tibetan medicine "Bangjian," have been integral to clinical practice for millennia. Despite their longstanding use, our understanding of the variation in chemical constituents and bioactive effects among different species is limited. AIM OF THE STUDY: In the present study, we aimed to assess the differences in chemical profiles and bioactivities among four Gentiana species (G. veitchiorum, G. trichotoma, G. crassuloides, and G. squarrosa) and explore potential bioactive markers. MATERIALS AND METHODS: The chemical composition of the four Gentiana species was analyzed using UPLC-QE-Orbitrap-MS. The antioxidant activity of the extracts was compared through DPPH, ABTS, and reducing power assays. The anti-inflammatory activity was evaluated by measuring the inhibitory effects on lipopolysaccharide-induced secretion of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) by RAW264.7 macrophages. Additionally, compounds strongly correlated with anti-inflammatory and antioxidant activities were identified through spectrum-effect relationship analysis. RESULTS: A total of 50 compounds were identified across the four Gentiana species. In vitro antioxidant assays demonstrated DPPH and ABTS scavenging abilities and reducing power within the concentration range of 62.5-2000 µg/mL. All four species inhibited the production of NO, IL-6, and TNF-α in RAW264.7 cells. Spectrum-effect relationship analysis revealed that gentiascabraside A, gentiatibetine, tachioside, lutonarin, and isotachioside were associated with the highest antioxidant activity; and swertiamarin, tarennoside, eleganoside C, and alpigenoside were associated with the highest anti-inflammatory activity. CONCLUSIONS: This study presents, for the first time, the chemical profiles and bioactivities of G. trichotoma, G. crassuloides, and G. squarrosa, which were comprehensively compared with those of G. veitchiorum. The findings provide novel insights to understand the traditional use and/or expand the current use of Gentiana species. Additionally, this research highlights the potential of Gentiana species as natural sources of antioxidants and anti-inflammatory agents, suggesting promising applications in tea production or medicinal contexts in the near future.

Dietary supplementation with Lactiplantibacillus plantarum P-8 improves the growth performance and gut microbiota of weaned piglets.

Weaning is a stressful event in the pig life cycle. We hypothesized that probiotics could be potential alternatives to antibiotics for promoting growth and ameliorating stress in weaning piglets via gut microbiota modulation and, thus, investigated the beneficial effects of dietary probiotic supplementation in weaning pigs. Ninety weaning piglets (Landrace × large white, 45 males and 45 females, 25 days of age) were randomized into three dietary treatments (30 piglets/treatment, divided into five replicates/treatment, i.e., six piglets/replicate) in this 28-day trial: control (C group, basal diet); probiotic [lactic acid bacteria (LAB) group, basal diet plus Lactiplantibacillus plantarum P-8]; and antibiotic (A group; basal diet plus chlortetracycline). The piglets' growth performance [average daily gain, average daily feed intake (ADFI), and feed conversion ratio (FCR)], immune and antioxidant markers, ileal mucosal morphology, and ileal and colonic microbiomes were compared among treatment groups. Compared to the C and A groups, probiotic supplementation significantly decreased the ADFI, FCR, and ileal mucosal crypt depth while increasing the villus height-to-crypt depth ratio, hepatic glutathione peroxidase and catalase activities, and serum levels of interleukin-2. Both probiotic and antibiotic treatments modulated the piglets' gut microbiomes, with more L. plantarum in the LAB group and more Eubacterium rectale and Limosilactobacillus reuteri in the A group. Probiotic supplementation significantly increased the relative abundance of genes encoding the acetylene, galactose, and stachyose degradation pathways, potentially enhancing nutrient absorption, energy acquisition, and growth performance. Probiotics are effective alternatives to antibiotics for promoting the health of piglets, possibly via gut microbiome modulation.IMPORTANCEWeaning impacts piglet health, performance, and mortality. Antibiotic treatment during weaning can mitigate the negative effects on growth. However, antibiotic use in livestock production contributes to the emergence of antibiotic resistance, which is a threat to global public health. This comprehensive study describes the gut microbial composition and growth performance of weaned piglets after dietary supplementation with Lactiplantibacillus plantarum P-8 or antibiotics. L. plantarum P-8 ameliorated stress and improved antioxidant capacity and growth performance in weaned piglets, accompanied by gut microbiota improvement. L. plantarum P-8 is an effective substitute for antibiotics to promote the health of weaned piglets while avoiding the global concern of drug resistance.

Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice.

Background and purpose: Silibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice. Experimental approach: After male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR. Results: The results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (ß-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated. Conclusion: The alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice.

Tumor Stimulus-Activatable Pretheranostic Agent: One Key to Three Locks.

The uncontrollable distribution of antitumor agents remains a large obstacle for specific and efficient cancer theranostics; thus, efficient construction of tumor-specific systems is highly desirable. In this work, a general design of tumor stimulus-activatable pretheranostic agents was put forward via a series of structures-tunable triphenylamine derivatives (TPA-2T-FSQ, TPA-2T-BSZ, and TPA-2T-ML) with phenothiazine, benzothiazine, and thiomorpholine as identifying groups of hypochlorite (HClO), respectively. Notably, the sulfur atom in phenothiazine of TPA-2T-FSQ was more easily oxidized to sulfoxide groups by HClO, transforming into an electron acceptor to form an excellent push-pull electronic system, which was beneficial to a large redshift of absorbance and emission wavelengths. Based on this, TPA-2T-FSQ resorted to a key of overexpressed HClO in the tumor to open "three locks", viz, NIR fluorescence, photothermal, and photoacoustic signals for multimodal diagnostic and treatment of the tumor. This study provided an elegant design to adopt tumor stimulus-triggerable pretheranostic for improving theranostic accuracy and efficiency, which was regarded as a promising candidate for precision medicine.

Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model.

BACKGROUND: High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear. OBJECTIVE: Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon. RESULTS: High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group. CONCLUSIONS: For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract.

Comprehensive Quality Evaluation of Polygonatum cyrtonema and Its Processed Product: Chemical Fingerprinting, Determination and Bioactivity.

Processing of Chinese herbal medicines (CHMs) is a traditional pharmaceutical technology in Chinese medicine. Traditionally, proper processing of CHMs is necessary to meet the specific clinical requirements of different syndromes. Processing with black bean juice is considered one of the most important techniques in traditional Chinese pharmaceutical technology. Despite the long-standing practice of processing Polygonatum cyrtonema Hua (PCH), there is little research on the changes in chemical constituents and bioactivity before and after processing. This study investigated the influence of black bean juice processing on the chemical composition and bioactivity of PCH. The results revealed significant changes in both composition and contents during processing. Saccharide and saponin content significantly increased after processing. Moreover, the processed samples exhibited considerably stronger DPPH and ABTS radical scavenging capacity, as well as FRAP-reducing capacity, compared to the raw samples. The IC50 values for DPPH were 1.0 ± 0.12 mg/mL and 0.65 ± 0.10 mg/mL for the raw and processed samples, respectively. For ABTS, the IC50 values were 0.65 ± 0.07 mg/mL and 0.25 ± 0.04 mg/mL, respectively. Additionally, the processed sample demonstrated significantly higher inhibitory activity against α-glucosidase and α-amylase (IC50 = 1.29 ± 0.12 mg/mL and 0.48 ± 0.04 mg/mL) compared to the raw sample (IC50 = 5.58 ± 0.22 mg/mL and 0.80 ± 0.09 mg/mL). These findings underscore the significance of black bean processing in enhancing the properties of PCH and lay the foundation for its further development as a functional food. The study elucidates the role of black bean processing in PCH and offers valuable insights for its application.

Yes-associated protein promotes the proliferation and differentiation of liver progenitor cells during liver fibrosis.

Liver fibrosis is closely related to the proliferation and differentiation of liver progenitor cells (LPCs). Yes-associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood. Using immunohistochemistry, immunofluorescence staining, quantitative PCR and Western blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs in either choline-deficient, ethionine-supplemented (CDE) diet or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced fibrotic mice, as well as in patients with liver fibrosis. By injecting adeno-associated virus vectors under the transcriptional control of Lgr5 promoter, we found that targeted knockdown of YAP in LPCs attenuated the CDE/DDC diet-induced ductular reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit-8 assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, spleen transplantation of YAP-overexpressing LPCs improved their ability to differentiate into hepatocytes and alleviated carbon tetrachloride-induced liver fibrosis. Collectively, our findings indicate that LPCs expansion and differentiation during liver fibrosis could be modulated by YAP, further suggesting the possibility of manipulating YAP expression in LPCs as a potential treatment for chronic liver diseases.

RAB11A Promotes Cell Malignant Progression and Tumor Formation of Prostate Cancer via Activating FAK/AKT Signaling Pathway.

Background: RAB11A, a member of the GTPase family, acts as a regulator in diverse cancers development. The dysregulation of the FAK/AKT signaling pathway is mainly related to tumorigenesis. This study aimed to investigate the possible effect of RAB11A in prostate cancer and further explore the potential mechanisms. Results: In this study, we illustrated the tumor-promoting effects of RAB11A based on in vivo and in vitro experiments. RAB11A expression was upregulated in prostate cancer cells. RAB11A knockdown decreased the prostate cancer cell proliferation, migration, and invasion. RAB11A also induced the epithelial-mesenchymal transition. PF562271 suppressed the malignant characteristics of prostate cancer cells caused by RAB11A knockdown. Furthermore, the interference of RAB11A reduced the tumor growth and the protein levels of p-FAK/FAK and p-AKT/AKT in vivo. Conclusion: RAB11A promotes cell malignant progression and tumor formation in prostate cancer via activating FAK/AKT signaling pathway.

Phytochemistry and Antioxidant Activities of the Rhizome and Radix of Millettia speciosa Based on UHPLC-Q-Exactive Orbitrap-MS.

The root of Millettia speciosa Champ. (MSCP) is used in folk medicine and is popular as a soup ingredient. The root is composed of the rhizome and radix, but only the radix has been used as a food. Thus, it is very important to compare the chemical components and antioxidant activities between the rhizome and radix. The extracts were analyzed by UHPLC-Q-Exactive Orbitrap-MS and multivariate analysis, and the antioxidant activities were evaluated by 2,20-azinobis (3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Ninety-one compounds were detected simultaneously and temporarily identified. Ten compounds were identified as chemical markers to distinguish the rhizome from the radix. The antioxidant activities of the radix were higher than the rhizome. Correlation analysis showed that uvaol-3-caffeate, 3-O-caffeoyloleanolic acid, and khrinone E were the main active markers for antioxidant activity, which allowed for the rapid differentiation of rhizomes and the radix. Therefore, it could be helpful for future exploration of its material base and bioactive mechanism. In addition, it would be considered to be used as a new method for the quality control of M. speciosa.

Alginate Alleviates Dextran Sulfate Sodium-Induced Colitis by Promoting Bifidobacterium animalis and Intestinal Hyodeoxycholic Acid Synthesis in Mice.

Alginate (ALG) is known to alleviate intestinal inflammation in inflammatory bowel disease, but its mechanism of action remains elusive. In the present study, we studied the involvement of the intestinal microbiota and bile acid (BA) metabolism in ALG-mediated anti-inflammatory effects in mice. A combination of 16S rRNA gene amplicon sequencing, shotgun metagenomic sequencing, and targeted BA metabolomic profiling was employed to investigate structural and functional differences in the colonic microbiota and BA metabolism in dextran sulfate sodium (DSS)-treated mice with or without dietary supplementation of ALG. We further explored the role of the intestinal microbiota as well as a selected ALG-enriched bacterium and BA in DSS-induced colitis. Dietary ALG alleviated DSS-mediated intestinal inflammation and enriched a small set of bacteria including Bifidobacterium animalis in the colon (P < 0.05). Additionally, ALG restored several bacteria carrying secondary BA-synthesizing enzymes such as 7α-hydroxysteroid dehydrogenase and BA hydrolase to healthy levels in DSS-treated mice. Although a majority of BAs were suppressed by DSS, a few secondary BAs such as hyodeoxycholic acid (HDCA) were markedly enriched by ALG. Furthermore, ALG significantly upregulated the expression of a major BA receptor, the farnesoid X receptor, while suppressing NF-κB and c-Jun N-terminal kinase (JNK) activation. Depletion of the intestinal microbiota completely abrogated the protective effect of ALG in DSS-treated mice. Similar to ALG, B. animalis and HDCA exerted a strong anti-inflammatory effect in DSS-induced colitis by downregulating inflammatory cytokines (interleukin-1ß [IL-1ß], IL-6, and tumor necrosis factor alpha [TNF-α]). Taken together, these results indicated that ALG achieves its alleviating effect on intestinal inflammation through regulation of the microbiota by enriching B. animalis to promote the biosynthesis of specific secondary BAs such as HDCA. These findings have revealed intricate interactions among the intestinal microbiota, BA metabolism, and intestinal health and further provided a novel strategy to improve intestinal health through targeted manipulation of the intestinal microbiota and BA metabolism. IMPORTANCE ALG has been shown to ameliorate inflammatory bowel disease (IBD), but little is known about the mechanism of its anti-inflammatory action. This study was the first to demonstrate that ALG provided a preventive effect against colitis in an intestinal microbiota-dependent manner. Furthermore, we confirmed that by selectively enriching intestinal B. animalis and secondary BA (HDCA), ALG contributed to the attenuation of DSS-induced colitis. These findings contribute to a better understanding of the mechanism of action of ALG on the attenuation of colitis and provide new approaches to IBD therapy by regulating gut microbial BA metabolism.

Bifidobacterium animalis Promotes the Growth of Weaning Piglets by Improving Intestinal Development, Enhancing Antioxidant Capacity, and Modulating Gut Microbiota.

Probiotics are widely used to promote performance and improve gut health in weaning piglets. Therefore, the objective of this study was to investigate the effects of dietary supplementation with Bifidobacterium animalis subsp. lactis (B. animalis) JYBR-190 on the growth performance, intestine health, and gut microbiota of weaning piglets. The results showed that the dietary addition of B. animalis significantly improved growth performance and decreased diarrhea incidence. B. animalis increased villus height in the duodenum and elevated goblet cell numbers and amylase activity in the jejunum. Additionally, B. animalis supplementation markedly increased total antioxidant capacity in jejunal mucosa but declined the malondialdehyde content. B. animalis treatment did not affect the mRNA expressions associated with the intestinal barrier and inflammatory cytokine in various intestinal segments. Microbiota analysis indicated that a diet supplemented with B. animalis significantly increased the relative abundances of health-promoting bacteria in the lumen, such as Streptococcus, Erysipelotrichaceae, Coprococcus, and Oscillibacter. There was a trend for B. animalis fed piglets to have a higher relative abundance of B. animalis in ileal digesta. Moreover, B. animalis-treated pigs decreased the abundance of Helicobacter and Escherichia-Shigella in ileal mucosa-associated microbiota. In summary, this study showed that B. animalis supplementation stimulated growth performance, improved gut development, enriched beneficial bacteria abundances, and declined intestinal pathogens populations, while B. animalis had limited effects on the intestinal barrier and immune function. IMPORTANCE In the modern swine industry, weaning is a critical period in the pig's life cycle. Sudden dietary, social, and environmental changes can easily lead to gut microbiota dysbiosis, diarrhea, and a decrease in growth performance. To stabilize intestinal microbiota and promote animal growth, antibiotics were widely applied in swine diets during the past few decades. However, the side effects of antibiotics posed a great threat to public health and food safety. Therefore, it is urgent to find and develop antibiotic alternatives. The growing evidence suggested that probiotics can be preferable alternatives to antibiotics because they can modulate microbiota composition and resist pathogens colonization. In this study, our results indicated that dietary supplementation with Bifidobacterium animalis promoted growth in weaning piglets by improving gut development, increasing beneficial bacteria abundances, and declining pathogens populations.

YAP affects the efficacy of liver progenitor cells transplantation in CCl4-induced acute liver injury.

The liver is a highly regenerative organ. During acute liver injury, the remaining hepatocytes rapidly proliferate to restore liver parenchyma and liver function. However, hepatocytes-driven regeneration is compromised in severe liver injury; instead, liver progenitor cells (LPCs) proliferate and differentiate into hepatocytes or cholangiocytes to restore mass and function of liver. The Hippo signaling pathway is of vital importance in liver regeneration, and Yes-associated protein (YAP) is the key component of the Hippo pathway. The therapeutic role of YAP has been well studied in hepatocytes-driven liver regeneration. However, the role of LPCs transplantation in acute liver injury has not been defined. Here, we investigated the therapeutic effect of splenic-transplantation of LPCs in CCl4-induced acute liver injury and explored the role of YAP during the procedure. LPCs isolated from choline-deficient, ethionine-supplemented diet (CDE) model were infected with GFP-YAP cDNA lentiviral vector, GFP-YAP shRNA lentiviral vector, and GFP lentiviral vector as control, respectively. At 48 h after CCl4 injection, PBS (control group), GFP lentiviral vector-infected LPCs (GFP-LPC group), GFP-YAP cDNA lentiviral vector-infected LPCs (YAP-LPC group) and GFP-YAP shRNA lentiviral vector-infected LPCs (sh-YAP-LPC group) were injected into spleens in CCl4-treated mice. Histological and serological analyses were performed to evaluate pathology and liver function. The effect of LPCs on the proliferation of hepatocytes and inflammation was investigated. We demonstrated that intra-splenic transplantation of LPCs alleviates CCl4-induced acute liver injury and YAP signaling acts a key role during the procedure. Further studies suggested that LPCs alleviate acute liver injury by promoting pre-existing hepatocytes proliferation rather than differentiating into hepatocytes. Furthermore, intra-splenic transplantation of LPCs attenuates inflammation, which facilitates tissue repair in acute liver injury. In conclusion, LPCs transplantation is a potential treatment for acute liver injury and YAP is a prospective therapeutic target in acute liver injury.

Dietary Supplementation of 25-Hydroxyvitamin D3 Improves Growth Performance, Antioxidant Capacity and Immune Function in Weaned Piglets.

This study was conducted to evaluate the effects of 25-hydroxyvitamin D3 (25(OH)VD3) and Vitamin D3 (VD3) supplemented in the diet of weaned piglets on their growth performance, bone quality, intestinal integrity, immune function and antioxidant capacity. A total of 192 weaned piglets were allocated into four groups and they were fed a control diet containing 2000 IU VD3 (negative control, NC), NC + 100 ppm colistin sulfate (positive control, PC), NC + 2000 IU VD3 (VD3) and NC + 2000 IU 25(OH)VD3 (25(OH)VD3). The results showed that 25(OH)VD3 improved the growth performance, bone quality and antioxidase activity of piglets compared with the other groups. Meanwhile, 25(OH)VD3 up-regulated ileal mRNA expressions of tight junction proteins and host defense peptides. The VD3 group had an increased intestinal sIgA content and mRNA expression of pBD-1 compared with the NC group. Both groups of VD3 and 25(OH)VD3 altered the microbial ß-diversity compared with the NC group, and 25(OH)VD3 increased ileal concentrations of acetate and butyrate. In conclusion, our findings indicated that a regular dosage of 2000 IU VD3 in the weaned piglets' diet did not achieve optimal antioxidant capacity and immune function. 25(OH)VD3 had better growth performance than VD3 at the same inclusion level, which is associated with the improved intestinal integrity and antioxidant capacity.

Exogenously Triggered Nanozyme for Real-Time Magnetic Resonance Imaging-Guided Synergistic Cascade Tumor Therapy.

The uncontrolled treatment process and high concentration of intracellular glutathione compromise the therapeutic efficacies of chemodynamic therapy (CDT). Here, iron oxide nanocrystals embedded in N-doped carbon nanosheets (IONCNs) are designed as a near-infrared light-triggered nanozyme for synergistic cascade tumor therapy. The IONCNs can absorb and convert 980 nm light to local heat, which induces the dissolution of iron oxide for generating Fe2+/Fe3+ in a weak acid environment, apart from thermal ablation of cancer cells. The formed Fe2+ takes on the active site for the Fenton reaction. The formed Fe3+ acts as glutathione peroxidase to magnify oxidative stress, improving the antitumor performance. The IONCNs can be used to visually track the treatment process via magnetic resonance imaging. Such IONCNs demonstrate great potential as an exogenously triggered nanozyme via an integrated cascade reaction for imaging-guided synergistic cancer therapy.

Consumption of Dietary Fiber with Different Physicochemical Properties during Late Pregnancy Alters the Gut Microbiota and Relieves Constipation in Sow Model.

Constipation is a common problem in sows and women during late pregnancy. Dietary fiber has potential in the regulation of intestinal microbiota, thereby promoting intestinal motility and reducing constipation. However, the effects of fibers with different physicochemical properties on intestinal microbe and constipation during late pregnancy have not been fully explored. In this study, a total of 80 sows were randomly allocated to control and one of three dietary fiber treatments from day 85 of gestation to delivery: LIG (lignocellulose), PRS (resistant starch), and KON (konjaku flour). Results showed that the defecation frequency and fecal consistency scores were highest in PRS. PRS and KON significantly increased the level of gut motility regulatory factors, 5-hydroxytryptamine (5-HT), motilin (MTL), and acetylcholinesterase (AChE) in serum. Moreover, PRS and KON promoted the IL-10 level and reduced the TNF-α level in serum. Furthermore, maternal PRS and KON supplementation significantly reduced the number of stillborn piglets. Microbial sequencing analysis showed that PRS and KON increased short-chain fatty acids (SCFAs)-producing genera Bacteroides and Parabacteroides and decreased the abundance of endotoxin-producing bacteria Desulfovibrio and Oscillibacter in feces. Moreover, the relative abundance of Turicibacter and the fecal butyrate concentration in PRS were the highest. Correlation analysis further revealed that the defecation frequency and serum 5-HT were positively correlated with Turicibacter and butyrate. In conclusion, PRS is the best fiber source for promoting gut motility, which was associated with increased levels of 5-HT under specific bacteria Turicibacter and butyrate stimulation, thereby relieving constipation. Our findings provide a reference for dietary fiber selection to improve intestinal motility in late pregnant mothers.

Effects of Moderate to High Static Magnetic Fields on Reproduction.

With the wide application of magnetic resonance imaging in hospitals and permanent magnets in household items, people have increased exposure to various types of static magnetic fields (SMFs) with moderate and high intensities, which has caused a considerable amount of public concern. Studies have shown that some aspects of gametogenesis and early embryonic development can be significantly affected by SMFs, while others have shown no effects. This review summarizes the experimental results of moderate to high-intensity SMFs (1 mT-16.7 T) on the reproductive development of different model animals, and we find that the effects of SMFs are variable depending on experimental conditions. In general, the effects of inhomogeneous SMFs seem to be more significant compared to that of homogeneous SMFs, which is likely due to magnetic forces generated by the magnetic field gradient. Moreover, some electromagnetic fields may have induced bioeffects because of nonnegligible gradient and heat effect, which are much reduced in superconducting magnets. We hope this review can provide a starting point for more in-depth analysis of various SMFs on reproduction, which is indispensable for evaluating the safety and potential applications of SMFs on living organisms in the future. © 2022 Bioelectromagnetics Society.

Dissecting the single-cell transcriptomeunderlying chronic liver injury.

Chronic liver disease (CLD) is currently a major health problem worldwide, which is accompanied by chronic liver injury and lack of clinically effective treatment; however, systematic characterization of chronic liver injury procedures at single-cell resolution is lacking. In the present study, we established chronic liver injury mouse models and conducted single-cell RNA sequencing (scRNA-seq), including choline-deficient, ethionine-supplemented (CDE) and 3,5-diethoxycarbonyl 1,4-dihydrocollidinen (DDC) mouse models. We captured in total 16,389 high-quality cells and identified 12 main cell types in scRNA-seq data. Macrophages and endothelial cells are the largest cell populations in our dataset. Transcriptional trajectory analysis revealed different expression patterns of cells between CDE and DDC models and identified potential liver injury markers, such as Ets1, Gda, Itgam, and Sparc. Differential analysis identified 25 and 152 differentially expressed genes in CDE and DDC macrophages, respectively. In addition, 413 genes were detected to exclusively express in specific pseudotime states of macrophages. These genes were found to participate in immune-related biological processes. Further cell-cell communication analysis found extensive receding of cell-cell interactions between different cell types in the liver injury process, especially in the DDC model. Our study characterized the single-cell transcriptional landscape in the process of chronic liver injury, promoting the understanding of the underlying molecular mechanisms and providing candidate clinical strategy for effective intervention of chronic liver diseases.

Moderate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS-Mediated Oxidative Stress.

Metastasis is the leading cause of cancer patient death, which is closely correlated with reactive oxygen species (ROS) levels. It is well known that the effects of ROS on tumors are diverse, depending on ROS concentration and cell type. We found that ovarian cancer cells have significantly lower levels of ROS than normal ovarian cells. Moreover, increased ROS levels in ovarian cancer cells can substantially inhibit their migration and invasion ability. Furthermore, the results show that moderate static magnetic field (SMF) can inhibit ovarian cancer cell migration, invasion, and stemness in a ROS-dependent manner. RNA sequencing results confirm that SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells. Consistently, the expressions of stemness-related genes were significantly decreased, including hyaluronan receptor (CD44), SRY-box transcription factor 2 (Sox2), and cell myc proto-oncogene protein (C-myc). Furthermore, moderate SMFs provided by a superconducting magnet and permanent magnet have good biosafety and can both inhibit ovarian cancer metastasis in mice. Therefore, our study demonstrates the effects of SMFs on oxidative stress and metastasis in the ovarian cancer cells, which reveals the potential of applying SMF as a physical method in cancer therapy in the future.

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.

BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.

Maternal galactooligosaccharides supplementation programmed immune defense, microbial colonization and intestinal development in piglets.

The benefits of galactooligosaccharides (GOS) in neonates have been confirmed. However, the effects of nutritional programming by maternal GOS intervention on microbial colonization and intestinal development in the offspring remain unclear. In the present study, late gestational sows were fed with GOS (10 g d-1 added into the diet) or not until parturition, and the performances, immune status, microbiota composition and intestinal barriers in their piglets on day 21 were compared. GOS supplementation in pregnant sows improved their litter characteristics and the growth performance of their piglets during the neonatal stage (day 21), and elevated the plasma IgA levels in both sows and their piglets (P < 0.05). GOS intervention enriched fecal Alloprevotella and Ruminoclostridium_1 in gestational sows and vertically increased fecal Alloprevotella and Ruminococcaceae in their piglets (P < 0.05). Moreover, maternal GOS intervention increased fecal acetate (P < 0.05) and improved the intestinal barriers of their piglets by upregulating intestinal tight junctions (Occludin, Claudin-1, ZO-1), the goblet cell number and Mucin-2 (P < 0.05), which correlated positively with the colonized microbiota (P < 0.05). In summary, GOS supplementation for sows during late gestation nutritionally programmed maternal specific microbes and IgA of their offspring. This neonatal programming showed positive potential in promoting the intestinal barriers, immune defense, and growth performance of the piglets. Our findings provide evidence for maternal nutritional programming in neonates and insights for future application of GOS in maternal-neonatal nutrition.