Gel immersion endoscopic mucosal resection for small gastric neoplastic lesions: A pilot study.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens.

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.

Oral administration enhances directly mucosal immune system in intestine of olive flounder (Paralichthys olivaceus).

Aquaculture is notably vulnerable to diseases, with Edwardsiella tarda causing significant mortality across various commercially important fish species in both freshwater and marine environments. In the aquaculture industry, sustainable disease control hinges on the effective development of vaccines. Oral vaccines present an appealing approach to immunization in fish due to their ease of antigen administration, reduced stress compared to non-oral delivery methods, and their potential applicability to both small and large finfish species. In mammals, the exposure of mucosal surfaces to antigens results in the secretion of antigen-specific IgA at these locations. Mammals have a common mucosal immune system, in which stimulation of one epithelium can also give rise to specific IgA or IgM responses in other mucosal organs. Mucosal immunoglobulins are particularly important in developing vaccines that provide mucosal immunity. However, it remains unclear whether fish share a common mucosal system. Moreover, neither Peyer's patches nor intestinal lymph nodes were identified. Nevertheless, oral vaccination remains an attractive method for inducing immunity. We investigated whether the activation of the mucosal immune response was induced by direct injection of the antigen. After oral antigen administration, antigen-specific antibody titers increased in the experimental group (E. tarda FKC vaccine). In the challenge experiment, the cumulative survival rate was 72% (E. tarda). This suggests that oral administration of antigens can activate intestinal mucosal immunity in flounders. Additionally, these results help understand the intestinal mucosal immune system of teleost fish. In the future, research on the signaling mechanisms of these genes is expected to provide helpful information for developing vaccine adjuvants.

ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and Inflammation.

BACKGROUND: The pathogenesis of Crohn's disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohn's disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation. METHODS: To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). We first examined trace element abundance in the colonic mucosal epithelium and lumen of homozygous A393T and wild-type (WT) mice to determine if the variant affected metal distribution. We also performed 16S rRNA gene sequencing on colon samples at 2 months, 3-4 months, and 12 months of age, and conducted histological scoring of colon tissue collected from 5-month and 10-month old mice. RESULTS: Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. 16S rRNA gene sequencing of colon samples revealed variant-linked effects on microbiome beta diversity in 2-month-, 3-4-month-, and 12-month-old mice. Histological scoring showed spontaneous intestinal inflammation in 10-month but not in 5-month-old mice. Lastly, predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc-, and cobalt-dependent pathways in A393T mice compared to wild-type controls. CONCLUSION: These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers.

Optimization of endoscopic treatment strategies for R0 resection of rectal neuroendocrine tumors smaller than 10mm.

BACKGROUND: The optimal histologically complete (R0) resection methods of endoscopy for rectal neuroendocrine tumor (NET) ≤ 10 mm remains controversial. We aimed to assess the optimal endoscopic treatments for NETs. METHODS: The retrospective enrolled patients (n = 208) with rectal NETs were divided into 3 subsets according to pathological tumor size: 2 - 3 mm, 4 - 5 mm, and 6 - 10 mm NETs. Factors associated with R0 resection according to different endoscopic treatments (accidental diagnostic biopsy by cold forceps, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)) and tumor size were investigated. All patients underwent follow-up and no local recurrence or metastasis were identified. RESULTS: A total of 208 patients were enrolled. In patients with 2 - 3 mm NETs, the R0 resection rate was 100.0% for biopsy, EMR, and ESD. The R0 resection rate for biopsy of 4 - 5 mm and 6 - 10 mm NETs was 34.3% and 0.0% respectively, which was inferior to the EMR/ESD rate (4 - 5mm: p < 0.001; 6 - 10 mm: p < 0.001: respectively). For patients with ≤ 10 mm NETs, EMR and ESD had a comparable en bloc (p = 0.082) and R0 resection rates (p = 0.651). CONCLUSION: Accidental diagnostic biopsy by cold forceps could be considered as the possible treatment for 2 - 3 mm rectal NETs. And for patients with ≤ 10 mm rectal NETs, both EMR and ESD might be sufficient.

Microbiome-Mucosal Immunity Nexus: Driving Forces in Respiratory Disease Progression.

The importance of the complex interplay between the microbiome and mucosal immunity, particularly within the respiratory tract, has gained significant attention due to its potential implications for the severity and progression of lung diseases. Therefore, this review summarizes the specific interactions through which the respiratory tract-specific microbiome influences mucosal immunity and ultimately impacts respiratory health. Furthermore, we discuss how the microbiome affects mucosal immunity, considering tissue-specific variations, and its capacity in respiratory diseases containing asthma, chronic obstructive pulmonary disease, and lung cancer. Additionally, we investigate the external factors which affect the relationship between respiratory microbiome and mucosal immune responses. By exploring these intricate interactions, this review provides valuable insights into the potential for microbiome-based interventions to modulate mucosal immunity and alleviate the severity of respiratory diseases.

Nasal flap preservation in endoscopic dacryocystorhinostomy for nasolacrimal duct obstruction.

AIM: To compare surgical outcomes between the conventional endoscopic dacryocystorhinostomy (DCR) and a modified endoscopic DCR for the treatment of nasolacrimal duct obstruction (NLDO), and evaluate factors associated with the surgical success rate. METHODS: Medical records of patients who underwent primary DCR surgery between January 2016 and July 2020 at the Otorhinolaryngology Department of Eye and Ear International Hospital, Lebanon were reviewed. RESULTS: The study group consisted of 50 consecutive modified endoscopic DCR and the control group consisted of 138 consecutive conventional endoscopic DCR. The success rates at 1y were 98.0% (49 out of 50) for modified DCR, significantly higher compared to 84.8% (117/138) for the conventional DCR; there was no significant difference in the success rate throughout the years in terms of both surgical techniques. The modified surgery vs traditional [adjusted odds ratio (aOR)=14.96] and having an adjunctive septoplasty surgery vs not (aOR=3.99) were significantly associated with higher odds of success. CONCLUSION: Mucosal flap preservation and apposition shows significant improvement in the surgical success rate. Moreover, there is no statistically significant difference found in terms of complication rate and mean operative time between the conventional and the modified techniques.

Fc-empowered exosomes with superior epithelial layer transmission and lung distribution ability for pulmonary vaccination.

Mucosal vaccines offer potential benefits over parenteral vaccines for they can trigger both systemic immune protection and immune responses at the predominant sites of pathogen infection. However, the defense function of mucosal barrier remains a challenge for vaccines to overcome. Here, we show that surface modification of exosomes with the fragment crystallizable (Fc) part from IgG can deliver the receptor-binding domain (RBD) of SARS-CoV-2 to cross mucosal epithelial layer and permeate into peripheral lung through neonatal Fc receptor (FcRn) mediated transcytosis. The exosomes F-L-R-Exo are generated by genetically engineered dendritic cells, in which a fusion protein Fc-Lamp2b-RBD is expressed and anchored on the membrane. After intratracheally administration, F-L-R-Exo is able to induce a high level of RBD-specific IgG and IgA antibodies in the animals' lungs. Furthermore, potent Th1 immune-biased T cell responses were also observed in both systemic and mucosal immune responses. F-L-R-Exo can protect the mice from SARS-CoV-2 pseudovirus infection after a challenge. These findings hold great promise for the development of a novel respiratory mucosal vaccine approach.

Usefulness of unwinding the colonoscope shaft loop via the universal cord for colorectal endoscopic resections.

The colonoscope shaft loop can be unwound by establishing a loop in the universal cord of the colonoscope to maintain the same endoscopic view during colorectal endoscopic resections.

Battle of the Gases: How Air and Nitrous Oxide Affect Endotracheal Tube Cuff Pressure During General Anesthesia.

Background Endotracheal tube (ETT) cuff pressure changes during general anesthesia. Endotracheal cuff pressure ideally should be maintained between 20 and 30 cm of H2O. Cuff pressure of less than 25 cm of H2O increases the chances of aspiration while pressure of more than 40 cm of H2O causes tracheal mucosa damage. The study aimed to monitor and compare variations of endotracheal cuff pressure during general anesthesia with oxygen-air or oxygen-nitrous oxide. Methods This prospective, randomized, double-blinded, observational study was conducted on 40 patients. After approval from the institutional ethics subcommittee, 40 patients of either gender, aged 18-60 years, belonging to ASA grades I and II, who were undergoing elective surgery under general anesthesia, were enrolled in this study. The patients were randomly divided into two groups, with 20 in each group. In Group A, oxygen-air and Group N, oxygen-nitrous oxide was used as a gaseous mixture in general anesthesia with ETT. The ETT cuff pressure was recorded with the help of a cuff manometer at intervals of five, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after intubation. If pressure was more than 40 cm of H2O, it was reduced to 25-30 cm of H2O. Data were collected and analyzed using methods described in Primer of Biostatistics by Stanton A. Glantz. Quantitative data were analyzed using the Student's t-test. Qualitative data were analyzed using the chi-square test. Results An increase in cuff pressure was noted more in Group N as compared to Group A. The pressure in the endotracheal cuff started to gradually increase after 30-40 minutes in Group N after intubation, while in Group A, there was no significant increase. The average number of times the cuff deflated was 0.2 ± 0.41 in Group A and 1.55 ± 0.51 in Group N, which was highly significant. Conclusion Changes in endotracheal cuff pressure were observed when using different gas mixtures for inflation. Specifically, cuff pressure increased with oxygen and nitrous oxide compared to oxygen with air. This suggests that anesthetic gas composition can impact cuff pressure, potentially affecting tracheal mucosal perfusion and patient safety. Therefore, regular monitoring and adjustment of cuff pressure is crucial, especially when using nitrous oxide, to prevent complications and ensure optimal patient care.

Oxymatrine alleviates NSAID-associated small bowel mucosal injury by regulating MIP-1/CCR1 signalling and gut microbiota.

Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1ß, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. ß diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of Ruminococcus 1, Oscillibacter and Prevotellaceae at the genus level as well as Lactobacillus SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of Allobaculum, Ruminococceos-UCG-005, Ruminococceos-NK4A214 and Clostridium associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.

Efficacy and safety of buccal midazolam for seizures outside the hospital: Real-world clinical experience.

INTRODUCTION: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice. METHODS: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023. RESULTS: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age. CONCLUSIONS: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

[Effect of Modified Xiaoyao Powder on intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease based on "gut-liver axis"].

This study explores the effects and mechanisms of Modified Xiaoyao Powder on the intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease(MAFLD) based on the " gut-liver axis". Sixty male C57BL/6 mice were randomly divided into the normal group, model group, bifidobacterium tetrad tablet group(SQ), and Modified Xiaoyao Powder groups with low,medium and high doses(XL, XM, XH), with 10 mice in each group. All the mice were administrated with a high-fat diet to build the MAFLD model except the normal group and then treated with related drugs for 12 weeks. Body mass, liver wet weight, and liver index were detected. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triacylglycerol(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and lipopolysaccharide(LPS)levels were detected using the biochemical kits. The contents of tumor necrosis factor-α(TNF-α) and interleukin(IL-6) in the liver were tested simultaneously. The morphological changes of the liver and intestine were observed using hematoxylin-eosin(HE) staining and oil red O staining. The goblet cells in the ileum were detected by periodic acid Schiff and alcian blue stain(AB-PAS) staining.The expression of zonula occludens-1(ZO-1), recombinant occludin(occludin), and recombinant claudin 1(claudin-1) in ileum and colon were detected by immunohistochemistry and Western blot. The changes of intestinal flora in mice were analyzed by 16S rRNA gene sequencing. The results showed that compared with the normal group, body weight, liver wet weight and liver index in the model group increased. The contents of TC, TG, ALT, AST, LDL-C, and LPS in the serum of the model group increased, while HDL-C decreased. Meanwhile, the contents of TNF-α and IL-6 in liver tissue increased and liver lipid accumulation increased, indicating successful model induction. Compared with the model group, body weight, liver wet weight, and liver index were decreased in XM,XH groups and SQ group. Serum levels of TC, TG, LDL-C, ALT and AST in XM group and SQ group were significantly decreased,and HDL-C levels were increased. The levels of IL-6, TNF-α in liver tissue and serum LPS in the XL, XM groups and SQ group were significantly decreased. The protein expression of claudin-1, occludin and ZO-1 in XL, XM groups and SQ group were increased. The analysis of intestinal flora showed that compared with the model group, Modified Xiaoyao Powder with a medium dose could significantly improve the richness and diversity of intestinal flora in mice. At the phylum level, the Firmicutes/Bacteroidetes(F/B) ratio decreased; at the genus level, Lactobacillus, Brautella, Bacteroides, and Ackermannia increased, while Prevotella, Desulfovibrio and Turicibacter decreased. The main differential species were Odorbacteraceaeae and Peptostreptococcaceae. In conclusion, Modified Xiaoyao Powder could inhibit inflammation, regulate intestinal flora homeostasis, and promote the repair of the intestinal mucosal barrier in mice with MAFLD.

Constructing the cGAMP-Aluminum Nanoparticles as a Vaccine Adjuvant-Delivery System (VADS) for Developing the Efficient Pulmonary COVID-19 Subunit Vaccines.

The cGAMP-aluminum nanoparticles (CAN) are engineered as a vaccine adjuvant-delivery system to carry mixed RBD (receptor-binding domain) of the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variant for developing bivalent pulmonary coronavirus disease 2019 (COVID-19) vaccines (biRBD-CAN). High phosphophilicity/adsorptivity made intrapulmonary CAN instantly form the pulmonary ingredient-coated CAN (piCAN) to possess biomimetic features enhancing biocompatibility. In vitro biRBD-CAN sparked APCs (antigen-presenting cells) to mature and make extra reactive oxygen species, engendered lysosome escape effects and enhanced proteasome activities. Through activating the intracellular stimulator of interferon genes (STING) and nucleotide-binding domain and leucine-rich repeat and pyrin domain containing proteins 3 (NALP3) inflammasome pathways to exert synergy between cGAMP and AN, biRBD-CAN stimulated APCs to secret cytokines favoring mixed Th1/Th2 immunoresponses. Mice bearing twice intrapulmonary biRBD-CAN produced high levels of mucosal antibodies, the long-lasting systemic antibodies, and potent cytotoxic T lymphocytes which efficiently erased cells displaying cognate epitopes. Notably, biRBD-CAN existed in mouse lungs and different lymph nodes for at least 48 h, unveiling their sustained immunostimulatory activity as the main mechanism underlying the long-lasting immunity and memory. Hamsters bearing twice intrapulmonary biRBD-CAN developed high resistance to pseudoviral challenges performed using different recombinant strains including the ones with distinct SARS-CoV-2-spike mutations. Thus, biRBD-CAN as a broad-spectrum pulmonary COVID-19 vaccine candidate may provide a tool for controlling the emerging SARS-CoV-2 variants.