Single-Atom Cu Nanozyme-Loaded Bone Scaffolds for Ferroptosis-Synergized Mild Photothermal Therapy in Osteosarcoma Treatment.

The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress-induced heat shock proteins (HSP). This study reports a new type of single-atom Cu nanozyme-loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca2+ , P5+ , Si4+ , and Cu2+ ). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.

Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis.

BACKGROUND: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma. Once at the sarcolemma, CD36 not only increases lipid uptake but also interacts with inflammatory receptor TLR4 (Toll-like receptor 4), together resulting in lipid-induced insulin resistance, inflammation, fibrosis, and cardiac dysfunction. Strategies inducing v-ATPase reassembly, that is, to achieve CD36 reinternalization, may correct these maladaptive alterations. For this, we used NAD+ (nicotinamide adenine dinucleotide)-precursor nicotinamide mononucleotide (NMN), inducing v-ATPase reassembly by stimulating glycolytic enzymes to bind to v-ATPase. METHODS: Rats/mice on cardiomyopathy-inducing high-fat diets were supplemented with NMN and for comparison with a cocktail of lysine/leucine/arginine (mTORC1 [mechanistic target of rapamycin complex 1]-mediated v-ATPase reassembly). We used the following methods: RNA sequencing, mRNA/protein expression analysis, immunofluorescence microscopy, (co)immunoprecipitation/proximity ligation assay (v-ATPase assembly), myocellular uptake of [3H]chloroquine (endosomal pH), and [14C]palmitate, targeted lipidomics, and echocardiography. To confirm the involvement of v-ATPase in the beneficial effects of both supplementations, mTORC1/v-ATPase inhibitors (rapamycin/bafilomycin A1) were administered. Additionally, 2 heart-specific v-ATPase-knockout mouse models (subunits V1G1/V0d2) were subjected to these measurements. Mechanisms were confirmed in pharmacologically/genetically manipulated cardiomyocyte models of lipid overload. RESULTS: NMN successfully preserved endosomal acidification during myocardial lipid overload by maintaining v-ATPase activity and subsequently prevented CD36-mediated lipid accumulation, CD36-TLR4 interaction toward inflammation, fibrosis, cardiac dysfunction, and whole-body insulin resistance. Lipidomics revealed C18:1-enriched diacylglycerols as lipid class prominently increased by high-fat diet and subsequently reversed/preserved by lysine/leucine/arginine/NMN treatment. Studies with mTORC1/v-ATPase inhibitors and heart-specific v-ATPase-knockout mice further confirmed the pivotal roles of v-ATPase in these beneficial actions. CONCLUSION: NMN preserves heart function during lipid overload by preventing v-ATPase disassembly.

Ferrous-sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows.

Pregnancy is a dynamic state involving rapid physiological changes in metabolism, affecting the health and development of the offspring. During pregnancy, the placenta constitutes a physical and immunological barrier to provide fetal nutrition through the maternal blood and prevent the exposure of the fetus to dangerous signals. Metabolic changes in the plasma, the fecal microbiota profile, and functional regulation in the placenta were studied in sows supplied with a ferrous-sucrose complex (FeSuc) from late gestation to parturition. The results revealed that maternal FeSuc supplementation enhanced arginine and proline metabolism, glutathione metabolism, with increased glutamic acid, beta-D-glucosamine, L-proline, 1-butylamine, and succinic acid and reduced sphingosine and chenodeoxycholic acid sulfate levels in the plasma. Moreover, significantly increased abundances of Christensenellaceae_R-7_group, Prevotellaceae_NK3B31_group, and Lachnospiraceae_NK4B4_group were detected in the feces of sows from the FeSuc group (P < 0.05). Spearman's correlation analysis indicated that Prevotellaceae_NK3B31_group abundances were positively correlated with glutamic acid, indoxyl sulfate, acetyl-DL-leucine, and beta-D-glucosamine, while Christensenellaceae_R-7_group was positively correlated with beta-D-glucosamine. Furthermore, maternal FeSuc supplementation significantly increased neonatal glucose (P < 0.01) and iron (P < 0.01) in the neonatal serum, significantly increased IL-10 and TGF-ß1 levels in the neonatal liver (P < 0.01) and jejunum (P < 0.05), promoted the transcription of immune molecules in the placenta, and significantly increased the protein expressions of EGF (P < 0.05), PI3K (P < 0.01), p-PI3K (P < 0.001), p-AKT (P < 0.01), and glucose transporter 1 (GLUT1) (P < 0.001) in the placenta. The current study demonstrated that FeSuc supplementation regulated maternal metabolism processes by altering the fecal microbial composition and improved neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows.

Enhanced glutathione production protects against zearalenone-induced oxidative stress and ferroptosis in female reproductive system.

Zearalenone (ZEN, a widespread fusarium mycotoxin) causes evoked oxidative stress in reproductive system, but little is known about whether this is involved in ferroptosis. Melatonin, a well-known antioxidant, has demonstrated unique anti-antioxidant properties in several studies. Here, this study was aimed to investigate whether ZEN-induced oxidative stress in female pig's reproductive system was involved in ferroptosis, and melatonin was then supplemented to protect against ZEN-induced abnormalities in vitro cell models [human granulosa cell (KGN) and mouse endometrial stromal cell (mEC)] and in vivo mouse model. According to the results from female pig's reproductive organs, ZEN-induced abnormalities in vulvar swelling, inflammatory invasion and pathological mitochondria, were closely linked with evoked oxidative stress. Using RNA-seq analysis, we further revealed that ZEN-induced reproductive toxicity was due to activated ferroptosis. Mechanistically, by using in vitro cell models (KGN and mEC) and in vivo mouse model, we observed that ZEN exposure resulted in oxidative stress and ferroptosis in a glutathione-dependent manner. Notably, these ZEN-induced abnormalities above were alleviated by melatonin supplementation through enhanced productions of glutathione peroxidase 4 and glutathione. Herein, the present results suggest that potential strategies to improve glutathione production protect against ZEN-induced reproductive toxicity, including oxidative stress and ferroptosis.

Stepwise co-fermented traditional Chinese medicine byproducts improve antioxidant and anti-inflammatory effects in a piglet model.

BACKGROUND: Lianhua Qingwen capsule is a traditional Chinese medicine (TCM) formula having antiviral and anti-inflammatory activities. During capsule production, a large amount of byproducts will be yielded and disposed of as waste by burying. Resourceful utilization of these kinds of TCM byproducts as feed additives through stage-based co-fermentation using enzyme and probiotics could reduce environmental stress and resource shortage. The in vitro characterization and the supplementary effects of fermented TCM byproducts (FTCM) for weaned piglets (initial body weight: 7.23 ± 0.33 kg; dose: basal diet + 300 mg kg-1 FTCM) were investigated. RESULTS: Higher reducing sugar content, total flavonoid content, flavonoid compounds (e.g. tectoridin, tricetin, flavone, apigenin, naringenin) and total antioxidant activity were determined in the FTCM compared to spontaneously fermented and unfermented materials. Supplementation of the FTCM to piglets did not significantly affect the feed intake, body weight gain and feed/gain ratio, but significantly decreased a proinflammatory cytokine, IL-8, and increased intestinal total antioxidant activity (TAC) and superoxide dismutase (SOD) activity. Moreover, FTCM supplementation increased α-diversity of the colonic microbiota accompanied with increased abundance of Prevotella genus and Treponema berlinense species. Correlation analysis indicates that T. berlinense is responsible for the decreased IL-8 level and enhanced intestinal TAC and SOD activities which might be mediated by a homoserine lactone molecule (3-oxo-C14). CONCLUSION: Overall, the stepwise co-fermentation enriched bioactive compounds within the TCM byproducts and their dietary supplementation did not generate any side effect on growth performance but displayed beneficial effects on enrichment of potential probiotic T. berlinense and relevant functions. © 2023 Society of Chemical Industry.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

[Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine].

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Development and characteristics of auricular fumigation moxibustion combined with heat-sensitive moxibustion device. / è€³ç†ç¸è”åˆçƒ­æ•ç¸è£ ç½®çš„ç ”åˆ¶ä¸Žç‰¹ç‚¹.

A moxibustion device with the functions of auricular fumigation moxibustion and heat-sensitive moxibustion is designed. The smoke of the ignited moxa stick is used for the fumigation moxibustion at the external auditory canal, while the heat generated works on Dazhui (GV 14) for heat-sensitive moxibustion. The device consists of five parts, i.e. combustion chamber, smoke pipe, smoke processing chamber, power module and connector. It solves the limitations such as unpleasant experience in treatment, unfavorable temperature control, easy scalding and excessive manual dependence induced by usual fumigation moxibustion and during heat-sensitive moxibustion. This moxibustion device may improve the safety and convenience when delivering the treatment with fumigation moxibustion and heat-sensitive moxibustion, as well as the work efficiency of medical staff.

In vitro antibacterial effects of Broussonetia papyrifera leaf extract and its anti-colitis in DSS-treated mice.

Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Nutrient content and resorption efficiency of leaves of broad-leaved trees along altitudes in Wuyi Mountains, China.

To reveal the variation of leaf nutrient utilization strategies with altitude gradient in subtropical mountain broadleaved trees, 44 species of broadleaved trees at different altitudes (1400, 1600 and 1800 m) in Wuyi Mountains were selected to measure nutrient content, stoichiometric ratio, and nutrient resorption efficiency of green and senescent leaves, and analyzed their allometric growth relationships. The results showed that nitrogen (N) and phosphorus (P) contents in green leaves were significantly higher than those in senescent leaves, which increased with the increases of altitude. The average values of phosphorus resorption efficiency (PRE) and nitrogen resorption efficiency (NRE) were 48.3% and 34.9%, respectively. PRE was significantly higher than NRE. There was no significant difference in nutrient resorption efficiency with altitude. NRE had positive isokinetic growth with and mature leaf N content at low altitude (1400 m) and negative allometry growth with senescent leaf N content at high altitude (1800 m). PRE and N and P contents of senescent leaves had negative isokinetic growth at low altitude (1400 m) and negative allometry growth at high altitudes (1600 and 1800 m). PRE-NRE allometric growth index was 0.95 at each altitude. The nutrient contents of green and senescent leaves increased with the increases of altitude, but altitude did not affect nutrient resorption efficiency. Plants preferred to re-absorbed P from senescent leaves. Nutrient resorption efficiency of leaves at high altitude affected the nutrient status of senescent leaves.

Research progress on drug delivery systems for curcumin in the treatment of gastrointestinal tumors.

Curcumin is a natural compound with a diketone structure, which can control the growth, metastasis, recurrence, neovascularization, invasion, and drug resistance of gastrointestinal tumors by inhibiting nuclear factor κB, overexpression of tumor cells, vascular endothelial growth factor, etc. However, due to the low bioavailability of curcumin formulation, it did not fully exert its pharmacological effects, and its application and development in the treatment of various malignant tumors are still limited. This review summarizes the research on drug delivery systems of curcumin combating digestive tract tumors in order to further reduce the toxic side effects of curcumin-containing drugs and fully exert their pharmacological activities, and improve their bioavailability and clinical value.

Effects of Maternal Dietary Enteromorpha prolifera Polysaccharide Iron Supplement on Mineral Elements and Iron Level of Neonatal Piglets.

Iron plays a key role in maternal health during pregnancy and fetal growth. Enteromorpha polysaccharide-iron (EP-Fe) as an organic iron chelate may improve the iron transmission of mother and offspring, ameliorate the poor pregnancy outcomes of sows, and alleviate the growth restriction of piglets caused by iron deficiency. This study aimed to evaluate the effects of maternal dietary supplementation with EP-Fe on reproductive performance and placental iron transmission of sows, as well as growth performance of piglets. Sixty pregnant sows at the 95th day of gestation were randomly divided into control group and EP-Fe group (EP-Fe, 139 mg kg-1). Blood samples of sows and neonatal piglets, colostrum, and tissue samples were collected on the day of delivery. The animal experiment ended at the 21st day of post-delivery. Results showed that maternal dietary EP-Fe increased colostrum iron (P < 0.05) of sows, as well as final litter weight (P < 0.05) and average daily weight of piglets (P < 0.05) during days 1-21 of lactation, as well as iron and manganese content in umbilical cord blood (P < 0.05) and hepatic iron of neonatal piglets (P < 0.01), and decreased fecal iron (P < 0.001), serum calcium (P < 0.05), phosphorus (P < 0.05), and zinc (P < 0.01) in the parturient sow. RT-qPCR results showed that Fpn1 and Zip14 in placenta, as well as TfR1 and Zip14 in duodenum of neonatal piglets, were activated by maternal EP-Fe supplement. These findings suggest that maternal dietary EP-Fe could increase iron storage of neonatal piglets via improving placental iron transport and iron secretion in colostrum, thus enhancing the growth performance of sucking piglets.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

[Progress of the application research of modern acupuncture anesthesia in perioperative period of thoracic surgery].

Modern acupuncture anesthesia is the application of acupuncture-related therapies to optimize the perioperative management which is based on the combined acupuncture-medicine anesthesia technology, and building a perioperative acupuncture anesthesia accelerated rehabilitation system. Based on the thoracic surgery, this paper analyzes and summarizes the application effects of modern acupuncture anesthesia, focusing on preoperative anxiety relief and advanced analgesia； reduce the dosage of anesthetics, stable respiration and hemodynamics, anti-stress and organ protection during surgery； postoperative analgesia, prevention of nausea, vomiting and cognitive impairment, improvement of gastrointestinal function, prevention of cognitive impairment, and enhancement of immunity. It is anticipated that this review may provide a basis for the further promotion and application of modern acupuncture anesthesia in clinical practice.

Ameliorative effects of silybin against avermectin-triggered carp spleen mitochondrial dysfunction and apoptosis through inhibition of PERK-ATF4-CHOP signaling pathway.

The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice.

Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation-exposed populations and patients who received radiotherapy.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. METHODS: Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. RESULTS: A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. CONCLUSION: In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.