Local hyperthermia mediated by gold nanoparticle-integrated silicone-covered stent: feasibility and tissue response in a rat esophageal model.

BACKGROUND: To assess the feasibility and tissue response of using a gold nanoparticle (AuNP)-integrated silicone-covered self-expandable metal stent (SEMS) for local hyperthermia in a rat esophageal model. METHODS: The study involved 42 Sprague-Dawley rats. Initially, 6 animals were subjected to near-infrared (NIR) laser irradiation (power output from 0.2 to 2.4 W) to assess the in vitro heating characteristics of the AuNP-integrated SEMS immediately after its placement. The surface temperature of the stented esophagus was then measured using an infrared thermal camera before euthanizing the animals. Subsequently, the remaining 36 animals were randomly divided into 4 groups of 9 each. Groups A and B received AuNP-integrated SEMS, while groups C and D received conventional SEMS. On day 14, groups A and C underwent NIR laser irradiation at a power output of 1.6 W for 2 min. By days 15 (3 animals per group) or 28 (6 animals per group), all groups were euthanized for gross, histological, and immunohistochemical analysis. RESULTS: Under NIR laser irradiation, the surface temperature of the stented esophagus quickly increased to a steady-state level. The surface temperature of the stented esophagus increased proportionally with power outputs, being 47.3 ± 1.4 °C (mean ± standard deviation) at 1.6 W. Only group A attained full circumferential heating through all layers, from the epithelium to the muscularis propria, demonstrating marked apoptosis in these layers without noticeable necroptosis. CONCLUSIONS: Local hyperthermia using the AuNP-integrated silicone-covered SEMS was feasible and induced cell death through apoptosis in a rat esophageal model. RELEVANCE STATEMENT: A gold nanoparticle-integrated silicone-covered self-expanding metal stent has been developed to mediate local hyperthermia. This approach holds potential for irreversibly damaging cancer cells, improving the sensitivity of cancer cells to therapies, and triggering systemic anticancer immune responses. KEY POINTS: • A gold nanoparticle-integrated silicone-covered self-expanding metal stent was placed in the rat esophagus. • Upon near-infrared laser irradiation, this stent quickly increased the temperature of the stented esophagus. • Local hyperthermia using this stent was feasible and resulted in cell death through apoptosis.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Mucosal immune responses and protective efficacy elicited by oral administration AMP-ZnONPs-adjuvanted inactivated H9N2 virus in chickens.

The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

A Novel Rat Model to Simulate the Benign Esophageal Stricture Induced by Endoscopic Submucosal Dissection.

Objective: This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD). Materials and Methods: Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery. Results: Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group. Conclusion: A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.

Polysaccharide from Atractylodes macrocephala Koidz Binding with Zinc Oxide Nanoparticles as a Novel Mucosal Immune Adjuvant for H9N2 Inactivated Vaccine.

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine's impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.

Randomized comparison of the four-hook anchor device and hook-wire use for the preoperative localization of pulmonary nodules.

OBJECTIVE: To compare the efficacy and safety of preoperative localization of small pulmonary nodules (SPNs) with 4-hook anchor device and hook-wire before video-assisted thoracoscopic surgery. METHODS: Patients with SPNs scheduled for computed tomography-guided nodule localization before video-assisted thoracoscopic surgery between May 2021 and June 2021 at our center were randomized to either 4-hook anchor group or hook-wire group. The primary end point was intraoperative localization success. RESULTS: After randomization, 28 patients with 34 SPNs were assigned to the 4-hook anchor group and 28 patients with 34 SPNs to the hook-wire group. The operative localization success rate was significantly greater in the 4-hook anchor group than in the hook-wire group (94.1% [32/34] vs 64.7% [22/34]; P = .007). All lesions in the 2 groups were successfully resected under thoracoscopy, but 4 patients in the hook-wire group who required transition from wedge resection to segmentectomy or lobectomy because of unsuccessful localization. Total localization-related complication rate was significantly lower in the 4-hook anchor group than in the hook-wire group (10.3% [3/28] vs 50.0% [14/28]; P = .004). The rate of chest pain requiring analgesia after the localization procedure was significantly lower in the 4-hook anchor group than in the hook-wire group (0 vs 5/28, 17.9%; P = .026). There were no significant differences in localization technical success rate, operative blood loss, hospital stay length and hospital cost between the 2 groups (all P > .05). CONCLUSIONS: The use of the 4-hook anchor device for SPN localization offers advantages over the traditional hook-wire technique.

Chitosan-coated artesunate protects against ulcerative colitis via STAT6-mediated macrophage M2 polarization and intestinal barrier protection.

Oral delivery of chitosan-coated artesunate (CPA) has been proven to be effective at preventing ulcerative colitis (UC) in mice. However, the anti-inflammatory mechanism is not fully understood. STAT6 is a key transcription factor that promotes anti-inflammatory effects by inducing M2 and Th2 dominant phenotypes, therefore we hypothesized STAT6 might play a key role in the process. To prove it, a STAT6 gene knockout macrophage cell line (STAT6-/- RAW264.7, by CRISPR/Cas9 method), and its corresponding Caco-2/RAW264.7 co-culture system combined with the STAT6 inhibitor (AS1517499, AS) in a mouse UC model were established and studied. The results showed that CPA remarkably suppressed the activation of TLR-4/NF-κB pathway and the mRNA levels of proinflammatory cytokines, while increased the IL-10 levels in RAW264.7. This effect of CPA contributed to the protection of the ZO-1 in Caco-2 which was disrupted upon the stimulation to macrophages. Simultaneously, CPA reduced the expression of CD86 but increase the expression of CD206 and p-STAT6 in LPS-stimulated RAW264.7 cells. However, above alterations were not obvious as in STAT6-/- RAW264.7 and its co-culture system, suggesting STAT6 plays a key role. Furthermore, CPA treatment significantly inhibited TLR-4/NF-κB activation, intestinal macrophage M1 polarization and mucosal barrier injury induced by DSS while promoted STAT6 phosphorylation in the UC mouse model, but this effect was also prominently counteracted by AS. Therefore, our data indicate that STAT6 is a major regulator in the balance of M1/M2 polarization, intestinal barrier integrity and then anti-colitis effects of CPA. These findings broaden our understanding of how CPA fights against UC and imply an alternative treatment strategy for UC via this pathway.

The inhibition effect of caffeic acid on NOX/ROS-dependent macrophages M1-like polarization contributes to relieve the LPS-induced mice mastitis.

The mammary gland is an adipose tissue containing not only adipocytes but also epithelial, endothelial, and immune cells. Epithelial cells and macrophages, as the integral components of the immune system, are on the front line of defense against infection. Our preliminary work proved that caffeic acid (CA) can effectively inhibit the inflammatory cascade of bovine mammary epithelial cells (BMEC) induced by lipopolysaccharide (LPS) and maintain cellular integrity and viability. Here, we investigated the therapeutic effect of CA on LPS-induced mice mastitis and explored its regulatory mechanism on macrophage inflammatory response induced by LPS in vitro. Firstly, the mice mastitis model was established by intramammary injection with 10 µg LPS, after which different CA doses (5, 10, 15 mg/kg) were administered. Then, the pathological section, myeloperoxidase (MPO) activity, proinflammatory factors and chemokines releasement, and redox state of mammary tissues were assessed, confirming CA's effectiveness on mice mastitis. In vitro, we validated the therapeutic relevance of CA in relieving LPS-induced RAW264.7 inflammatory and oxidative stress responses. Moreover, we further provided evidence that CA significantly reduced LPS-induced reactive oxygen species (ROS) generation via NADPH oxidase (NOX), which improved the imbalance relationship between nuclear factor kappa-B (NF-κB) and NF-E2 p45-related factor 2 (Nrf2) and led to a marked weakening of M1 polarization. The NOX-ROS signal inhibited by CA weakened the oxidative burst and neutrophil chemotaxis of macrophages, thus alleviating the immune cascade in mammary gland tissue and reducing the LPS-induced inflammatory damage. Collectively, CA would be a potential candidate or antibacterial synergist for curbing mastitis.

Therapeutic effect of a self-made herbal formula on a multi-drug resistant Eimeria tenella isolate infection in broiler chickens.

In-feed prophylactic chemotherapy is widely considered the mainstay of avian coccidiosis control, while serious drug resistance strictly restricts its application. Confronted with the urgent need for an alternative strategy, a traditional Chinese medicine formula (TCMF) was developed. Meanwhile, its potential to iron out complicated clinical coccidiosis was scrutinized in vivo with a field-isolated multi-drug resistant Eimeria tenella (E. tenella) isolate. Birds were inoculated with 5 × 104 sporulated oocysts and administrated with TCMF supplementation in water from 72 h post-infection to the end of the experiment, diclazuril (DIC) was set as a positive control. As a result, TCMF intervention reduced oocyst shedding, cecal lesion and mortality, and enhanced body weight gain. According to the above, anticoccidial index (ACI) was calculated and TCMF exerted a moderate anticoccidial activity. Besides, macroscopic, histopathological, and ultrastructural observations revealed the safeguarding effects of TCMF on E. tenella-induced cecal injury. Following, TCMF treatment presented an obvious inhibition effect on E. tenella caused oxidative stress and inflammatory response. Moreover, TCMF supplementation restored the cecal flora abundance and diversity, reduced the colonization of harmful bacteria, and increased the probiotics abundance. In conclusion, TCMF exhibited a moderate anticoccidial effect along with alleviating E. tenella-induced cecal injury, redox imbalance, and inflammatory response which may be associated with the microflora modulatory effect.

AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression.

A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have established AKIP1's malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression.

The synergy of tea tree oil nano-emulsion and antibiotics against multidrug-resistant bacteria.

AIMS: We determined the synergistic effects of tea tree essential oil nano-emulsion (nanoTTO) and antibiotics against multidrug-resistant (MDR) bacteria in vitro and in vivo. Then, the underlying mechanism of action of nanoTTO was investigated. METHODS AND RESULTS: Minimum inhibitory concentrations and fractional inhibitory concentration index (FICI) were determined. The transepithelial electrical resistance (TEER) and the expression of tight junction (TJ) protein of IPEC-J2 cells were measured to determine the in vitro efficacy of nanoTTO in combination with antibiotics. A mouse intestinal infection model evaluated the in vivo synergistic efficacy. Proteome, adhesion assays, quantitative real-time PCR, and scanning electron microscopy were used to explore the underlying mechanisms. Results showed that nanoTTO was synergistic (FICI ≤ 0.5) or partial synergistic (0.5 < FICI < 1) with antibiotics against MDR Gram-positive and Gram-negative bacteria strains. Moreover, combinations increased the TEER values and the TJ protein expression of IPEC-J2 cells infected with MDR Escherichia coli. The in vivo study showed that the combination of nanoTTO and amoxicillin improved the relative weight gain and maintained the structural integrity of intestinal barriers. Proteome showed that type 1 fimbriae d-mannose specific adhesin of E. coli was downregulated by nanoTTO. Then, nanoTTO reduced bacterial adhesion and invasion and inhibited the mRNA expression of fimC, fimG, and fliC, and disrupted bacterial membranes.

Free Radical and Viral Infection: A Review from the Perspective of Ferroptosis.

Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), play critical roles in various physiological activities such as cell differentiation, apoptosis, and vascular tension when existing in cells at low levels. However, excessive amounts of free radicals are harmful, causing DNA damage, lipid peroxidation, protein degeneration, and abnormal cell death. Certain viral infections induce cells to produce excessive free radicals, which in multiple ways help the virus to replicate, mature, and exit. Iron is a necessary element for many intracellular enzymes, involved in both cellular activities and viral replication. Ferroptosis, a programmed cell death mode distinct from apoptosis, necrosis, and pyroptosis, is characterized by lipid peroxide accumulation and damage to the antioxidant system, affecting many cellular processes. Viral infection commonly manifests as decreased glutathione (GSH) content and down-regulated glutathione peroxidase 4 (GPX4) activity, similar to ferroptosis. Recent studies have suggested a possible relationship among free radicals, viral infections and ferroptosis. This review aims to elucidate the molecular mechanism linking free radicals and ferroptosis during viral infections and provide a new theoretical basis for studying viral pathogenesis and control.

Infigratinib, a Selective Fibroblast Growth Factor Receptor Inhibitor, Suppresses Stent-Induced Tissue Hyperplasia in a Rat Esophageal Model.

PURPOSE: Stent-induced tissue hyperplasia remains a challenge for the application of self-expanding metal stents in the management of esophageal stricture. This study aimed to evaluate the efficacy of infigratinib, which is a selective fibroblast growth factor receptor inhibitor, in the prevention of stent-induced tissue hyperplasia in a rat esophageal model. METHODS: Twenty-four male Sprague-Dawley rats underwent esophageal stent placement and were randomized to receive 1 ml of vehicle, 5 mg/kg infigratinib in 1 ml of vehicle, or 10 mg/kg infigratinib in 1 ml of vehicle via naso-gastric tube once daily for 28 days. Follow-up fluoroscopy was performed on postoperative day 28, and the stented esophageal tissues were harvested for histological and immunofluorescence examinations. RESULTS: All rats survived until euthanasia on postoperative day 28 without procedure-related adverse events. The incidence of stent migration was 12.5%, 12.5% and 25% in the control group, the 5 mg/kg infigratinib group and, the 10 mg/kg infigratinib group, respectively. The percentage of granulation tissue area, the submucosal fibrosis thickness, the number of epithelial layers, the degree of inflammatory cell infiltration, the degree of collagen deposition, the number of fibroblast growth factor receptor 1 (FGFR1)-expressing myofibroblasts, and the number of proliferating myofibroblasts were all significantly lower in both infigratinib groups than in the control group (P < 0.05) but were not significantly different between the two infigratinib groups (P > 0.05). CONCLUSIONS: Infigratinib significantly suppresses stent-induced tissue hyperplasia by inhibiting FGFR1-mediated myofibroblast proliferation and profibrotic activities in a rat esophageal model.

MicroRNAs reshape the immunity of insects in response to bacterial infection.

The interaction between bacteria and insects can significantly impact a wide range of different areas because bacteria and insects are widely distributed around the globe. The bacterial-insect interactions have the potential to directly affect human health since insects are vectors for disease transmission, and their interactions can also have economic consequences. In addition, they have been linked to high mortality rates in economically important insects, resulting in substantial economic losses. MicroRNAs (miRNAs) are types of non-coding RNAs involved in regulating gene expression post-transcriptionally. The length of miRNAs ranges from 19 to 22 nucleotides. MiRNAs, in addition to their ability to exhibit dynamic expression patterns, have a diverse range of targets. This enables them to govern various physiological activities in insects, like innate immune responses. Increasing evidence suggests that miRNAs have a crucial biological role in bacterial infection by influencing immune responses and other mechanisms for resistance. This review focuses on some of the most recent and exciting discoveries made in recent years, including the correlation between the dysregulation of miRNA expression in the context of bacterial infection and the progression of the infection. Furthermore, it describes how they profoundly impact the immune responses of the host by targeting the Toll, IMD, and JNK signaling pathways. It also emphasizes the biological function of miRNAs in regulating immune responses in insects. Finally, it also discusses current knowledge gaps about the function of miRNAs in insect immunity, in addition to areas that require more research in the future.

Caffeic acid, but not ferulic acid, inhibits macrophage pyroptosis by directly blocking gasdermin D activation.

Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro-inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well-known antioxidant and anti-inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin-induced canonical and cytosolic lipopolysaccharide (LPS)-induced non-canonical pyroptosis and alleviates LPS-induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS-challenged mice and blocked proinflammatory cytokine secretion. The anti-pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis-associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N-GSDMD pore construction and less cellular content release. In LPS-induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin-1ß and tumor necrosis factor-α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis-associated disease.

Eugenol alleviates Salmonella Typhimurium-infected cecal injury by modulating cecal flora and tight junctions accompanied by suppressing inflammation.

BACKGROUND: Salmonella enterica serovar Typhimurium (ST) mainly exists in poultry and poultry related products, which are common sources of human salmonellosis. So, ST is an important zoonotic pathogen that threatens public health and safety. Eugenol has been noted for its antibacterial and anti-inflammatory properties, and it is expected to develop into an antibacterial therapy in vivo. METHODS: Herein, the effects of eugenol against ST infection in terms of intestinal flora, cecal tight junction, and cecal inflammation in broilers was evaluated in this study. RESULTS: The results showed that oral eugenol pretreatment obviously relieved the histopathological changes and ultrastructural injury of cecum caused by ST infection. Further analysis found that eugenol lessened the number of ST in the cecum, restrained Proteobacteria and Ruminococcus, and kept the ratio of Firmicutes to Bacteroidetes (F/B), improved the relative abundance of Alistipes compared to the infection control. Moreover, eugenol sustained the expression of ZO-1, claudin-1, and occluding tight junction proteins, reduced the mRNA levels of myeloid differentiation factor 88 (MyD88), toll-like receptor-4 (TLR4) and inducible nitric oxide synthesis (iNOS), suppressed the phosphorylation of p65 and IκBα in the NF-κB signaling pathway, as well as the mRNA levels of TNF-α, IL-1ß, IL-2, and IL-18 in the cecum tissue. CONCLUSION: Taken together, eugenol could protect broilers against ST infection via maintaining intestinal flora, tight junctions involved in mucosal barrier function, then accordingly limiting the excessive inflammation, finally contributed to improving relative weight gains and survival rates of broilers.

Modified Patent Hemostasis Strategy Based on the Platelet Counts for Transradial Access Chemoembolization in Patients with Hepatocellular Carcinoma: A Prospective Single-Center Study.

Objective: This study aimed to investigate the shortest compression time to achieve hemostasis and the optimal hemostasis strategy in patients treated with transradial access chemoembolization (TRA-TACE). Methods: From October 2019 to October 2021, 119 consecutive patients with hepatocellular carcinoma (HCC) who underwent 134 sessions of TRA-TACE were included in this prospective single-center study. The compression time was measured by decompressing the device for 30 min, and thereafter, every 10 min after the procedure until complete hemostasis was achieved. Results: Technical success was achieved for all TRA procedures. None of the patients experienced major TRA-related adverse events. Minor adverse events occurred in 7.5% of the patients. The mean compression time was 31.8 ± 5.0 min. Factors that may impact hemostasis were analyzed by univariate and multivariate analyses, and a platelet count < 100×109 /L (p = 0.016, odds ratio = 3.942) was found to be an independent factor that could predict the failure to achieve hemostasis within 30 min. For patients with a platelet count < 100×109 /L, the compression time required to achieve hemostasis was 60 min. For patients with a platelet count ≥ 100×109 /L, the compression time required to achieve hemostasis was 40 min. Conclusion: To achieve hemostasis in patients with HCC treated with TRA-TACE, compression for 60 min is sufficient for those with a platelet count < 100×109 /L, and compression for 40 min is sufficient for those with a platelet count ≥ 100×109 /L.

The Prevalence of Plasmid-Mediated Colistin Resistance Gene mcr-1 and Different Transferability and Fitness of mcr-1-Bearing IncX4 Plasmids in Escherichia coli from Pigeons.

The prevalence of colistin-resistant bacteria limited the usage of colistin in the treatment of clinical multidrug-resistant Gram-negative bacterial infections. Here, we aimed to investigate the prevalence and molecular characterization of mcr-1-carrying isolates from pigeons close to humans following the ban on the use of colistin as an animal feed additive in China. Methods, including PCR, antimicrobial susceptibility testing, conjugation experiments, plasmid replicon typing, genome sequencing, bioinformatics analysis, measurement of growth curves, competition experiments, and plasmid stability assays were used to identify and characterize mcr-1-positive isolates. In total, 45 mcr-1-positive E. coli isolates were acquired from 100 fecal samples, and MICs of colistin ranged from 4 to 8 mg/L. The prevalence of mcr-1-positive E. coli isolates from pigeons was mainly mediated by IncX4 plasmids (39/45), including transferable mcr-1-bearing IncX4 plasmids with fitness advantage in 21 isolates, and nontransferable mcr-1-bearing IncX4 plasmids with fitness disadvantage in 18 isolates. There is a similar structure among the 6 mcr-1-bearing nontransferable IncX4 plasmids and 10 mcr-1-bearing transferable IncX4 plasmids in 16 E. coli isolates that have been sequenced. Plasmid transferability evaluation indicated that the same IncX4 plasmid has different transferability in different E. coli isolates. In conclusion, this study demonstrates that pigeons could act as potential reservoirs for the spread of mcr-1-positive E. coli in China. Transferability of IncX4 plasmids may be influenced by host chromosome in the same bacterial species. Additional research on the factors influencing the transferability of IncX4 plasmids in different bacterial hosts is required to help combat antimicrobial resistance. IMPORTANCE The emergence of plasmid-mediated colistin resistance gene mcr-1 incurs great concerns. Since the close proximity of pigeons with humans, it is significant to understand the prevalence and molecular characterization of mcr-1-positive isolates in pigeons, to provide a rationale for controlling its spread. Here, we found that the prevalence of mcr-1-positive E. coli from pigeons was mainly mediated by IncX4 plasmids. However, different transferability and fitness of mcr-1-bearing IncX4 plasmids in E. coli were observed, which demonstrated that transferability of IncX4 plasmids could be affected not only by genes on plasmids, but also by chromosomal factors in the same bacterial species. Our finding provided a new insight on studying the factors influencing the transferability of plasmids.

Tea tree oil nanoliposomes: optimization, characterization, and antibacterial activity against Escherichia coli in vitro and in vivo.

The purpose of this study was to formulate tee tree oil nanoliposomes (TTONL) and evaluate its characterization and antibacterial activity. TTONL was prepared by thin film hydration and sonication technique, and the preparation conditions were optimized by Box-behnken response surface method. The characterization (morphology, size, zeta potential, and stability) and antibacterial activity of TTONL against Escherichia coli (E. coli) in vitro and in vivo were evaluated. The optimal preparation conditions for TTONL: lecithin to cholesterol mass ratio of 3.7:1, TTO concentration of 0.5%, and pH of the hydration medium of 7.4, which resulted in a TTONL encapsulation rate of 80.31 ± 0.56%. TTONL was nearly spherical in shape and uniform in size, and the average particle size was 227.8 ± 25.3 nm with negative charge. The specific disappearance of the TTO peak in the infrared spectrum suggested the successful preparation of TTONL, which showed high stability at 4°C within 35 d. The result of MIC test found that the nanoliposomes improved antibacterial activity of TTO against various E. coli strains. TTONL exposure in vitro caused different degrees of structural damage to the E. coli. TTONL by oral administration alleviated the clinical symptoms and intestinal lesion of chickens induced with E. coli challenge. Furthermore, TTONL treatment remarkably lowered the mRNA expression of NLRP3 and NF-κB (p65) in the duodenum and cecum of E. coli-infected chickens. In conclusion, the prepared TTONL had good stability and slow-release property with dose-dependent inhibition and killing effects on different strains of E. coli, and exerted a preventive role against chicken colibacillosis through inhibition.

Moringa oleifera leaf polysaccharide alleviates experimental colitis by inhibiting inflammation and maintaining intestinal barrier.

The characteristic of ulcerative colitis (UC) is extensive colonic mucosal inflammation. Moringa oleifera (M. oleifera) is a medicine food homology plant, and the polysaccharide from M. oleifera leaves (MOLP) exhibits antioxidant and anti-inflammatory activity. The aim of this study to investigate the potential effect of MOLP on UC in a mouse model as well as the underlying mechanism. Dextran sulfate sodium (DSS) 4% in drinking water was given for 7 days to mice with UC, at the same time, MOLP (25, 50, and 100 mg/kg/day) was intragastric administered once daily during the experiment. Structural analysis revealed that MOLP had an average molecular weight (Mw) of 182,989 kDa and consisted of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galactose uronic acid, glucuronic acid, glucose uronic acid and mannose uronic acid, with a percentage ratio of 1.64, 18.81, 12.04, 25.90, 17.57, 12.01, 3.51, 5.28, 0.55, 1.27, and 1.43%, respectively. In addition, the features of MOLP were identified by Fourier-transform infrared (FT-IR) and spectra, X-ray diffraction (XRD). The results showed that MOLP exhibited protective efficacy against UC by alleviating colonic pathological alterations, decreasing goblet cells, crypt destruction, and infiltration of inflammatory cells caused by DSS. Furthermore, MOLP notably repressed the loss of zonula occludens-1 (ZO-1) and occludin proteins in mucosal layer, as well as up-regulating the mRNA expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-γ (PPAR-γ), whereas down-regulating the activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB) signaling pathway and the production of pro-inflammatory cytokines. Therefore, these results will help understand the protective action procedure of MOLP against UC, thereby providing significance for the development of MOLP.