BACKGROUND: The cytokine storm triggered by sepsis can lead to the development of acute lung injury (ALI). Human umbilical cord Mesenchymal stem cells derived exosomes (HucMSCs-EXOs) have been demonstrated to possess immunosuppressive and anti-inflammatory properties. Programmed cell death receptor 1 (PD-1) plays a crucial role in maintaining the inflammatory immune homeostasis. The aim of this study is to investigate the synergistic therapeutic effect of EXOs loaded with anti-PD-1 peptide on septic-ALI.
METHODS: This study prepares a novel EXOs-based drug, named MEP, by engineering modification of HucMSCs-EXOs, which are non-immunogenic extracellular vesicles, loaded with anti-PD-1 peptide. The therapeutic effect and potential mechanism of MEP on septic-ALI are elucidated through in vivo and in vitro experiments, providing experimental evidence for the treatment of septic acute lung injury with MEP.
RESULTS: We found that, compared to individual components (anti-PD-1 peptide or EXOs), MEP treatment can more effectively improve the lung injury index of septic-ALI mice, significantly reduce the expression levels of inflammatory markers CRP and PCT, as well as pro-inflammatory cytokines TNF-α and IL-1β in serum, decrease lung cell apoptosis, and significantly increase the expression of anti-inflammatory cytokine IL-10 and CD68+ macrophages. In vitro, MEP co-culture promotes the proliferation of CD206+ macrophages, increases the M2/M1 macrophage ratio, and attenuates the inflammatory response. GEO data analysis and qRT-PCR validation show that MEP reduces the expression of inflammasome-related genes and M1 macrophage marker iNOS.
CONCLUSIONS: In both in vitro and in vivo settings, MEP demonstrates superior therapeutic efficacy compared to individual components in the context of septic-ALI.

BACKGROUND: Eczema, an inflammatory skin disease causing intense itching, is a function of a range of internal and external factors, impacting individuals of all ages and leading to economic loss. Inflammation is the most important manifestation of eczema, and Matricaria recutita essential oil (MREO) extracted from Matricaria recutita possesses excellent antibacterial and anti-inflammatory properties.
METHODS: In this study, Matricaria recutita microemulsions were prepared by the trans-phase emulsification method and their stability was determined by evaluating the relevant indexes. Establishment of 2,4-dinitro-chlorobenzene-induced AD model in mice. Detection of serum indexes of IL-6, IL-17, and TNF-α, and on pathological tissue sections, the HE staining, toluidine blue staining, immunohistochemistry, and observation were performed.
RESULTS: The study obtained optimal conditions for the preparation of microemulsion formulations of Matricaria recutita. Through quality evaluation, it was found that the microemulsion increased stability, reduced irritation, and retained anti-inflammatory activity and therapeutic effects on eczema compared to Matricaria recutita essential oil (MREO). Studies have demonstrated that microemulsion formulations of Matricaria recutita and Matricaria recutita significantly down regulate the proinflammatory factors TNF-α, IL-17, and IL-6. It was shown by hematoxylin-eosin (HE) staining that both Matricaria recutita essential oil (MREO) and Matricaria recutita microemulsion (MRME) improved the inflammatory status of eczematous skin tissues in mice. The number of mast cells expressed in the tissues was decreased in the surface-treated group, as shown by toluidine blue staining. Additionally, the number of mast cells expressed in the tissues in the surface-treated group was reduced, as demonstrated by immunohistochemistry. Furthermore, immunohistochemistry revealed that MREO and MRME have immunomodulatory effects on the tissues.
CONCLUSIONS: The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

Sepsis is recognized as a syndrome of systemic inflammatory reaction induced by dysregulation of the body\'s immunity against infection. The multiple organ dysfunction associated with sepsis is a serious threat to the patient\'s life. Endothelial cell dysfunction has been extensively studied in sepsis. However, the role of macrophages in sepsis is not well understood and the intrinsic link between the two cells has not been elucidated. Macrophages are first-line cells of the immune response, whereas endothelial cells are a class of cells that are highly altered in function and morphology. In sepsis, various cytokines secreted by macrophages and endothelial cell dysfunction are inextricably linked. Therefore, investigating how macrophages affect endothelial cells could offer a theoretical foundation for the treatment of sepsis. This review links molecules (TNF-α, CCL2, ROS, VEGF, MMP-9, and NO) secreted by macrophages under inflammatory conditions to endothelial cell dysfunction (adhesion, permeability, and coagulability), refining the pathophysiologic mechanisms of sepsis. At the same time, multiple approaches (a variety of miRNA and medicines) regulating macrophage polarization are also summarized, providing new insights into reversing endothelial cell dysfunction and improving the outcome of sepsis treatment.

Chronic rhinosinusitis with nasal polyps is a common chronic inflammatory disease with significant tissue remodeling, but the mechanism of remodeling remains unclear. Studies have shown that Type（T） 2 inflammatory network plays a crucial role in tissue remodeling and nasal polyp formation. Clinical trials have been carried out for several biological targets, and a number of potential therapeutic targets have received increasing attention. This paper will summarize the research progress of T2 inflammatory response involved in nasal polyp tissue remodeling to provide ideas for further exploring the mechanism of nasal polyp tissue remodeling.
摘要：慢性鼻窦炎伴鼻息肉是常见的慢性炎性疾病，伴有明显的组织重塑，其重塑机制尚不明确。研究发现T2型炎症网络在组织重塑及鼻息肉形成过程中发挥至关重要的作用，并已针对多个生物靶点开展临床试验，还有若干潜在的治疗靶点受到越来越多的关注。本文将归纳总结T2型炎症反应参与鼻息肉组织重塑的研究进展，以期为进一步探究鼻息肉组织重塑的发生机制提供思路。.

BACKGROUND: Prolonged alcohol consumption may lead to gastrointestinal tract dysfunction and cause abnormalities in the associated nervous system activity, thereby increasing the body\'s craving for alcohol. Lactobacillus casei is a probiotic that has been shown to reduce the incidence of alcohol-related diseases. However, it is unclear whether Lactobacillus casei can delay the development of alcohol dependence.
METHODS: The chronic intermittent active drinking method was used to establish a mouse alcohol dependence model. The mice were randomly divided into 4 treatment groups, as follows: (1) Control group: two bottles of distilled water alternately, 0.2 mL/d saline gavage. (2) Alcohol group: alternating water and alcohol, 0.2 mL/d saline gavage. (3) Low group: alternating water and alcohol, 0.2 mL/d 1 × 108CFU of Lactobacillus casei by gavage. (4) High group: alternating water and alcohol, 0.2 mL/d 1 × 109CFU of Lactobacillus casei by gavage. The daily water consumption (mL), alcohol consumption (mL) and body weight of each mouse were recorded. After that, pathological changes in the intestines, brain tissues and serum of the experimental animals were detected, while changes in the intestinal flora of the mice were analysed by 16S rRNA sequencing.
RESULTS: The Lactobacillus casei intervention did not produce a significant effect on body weight in alcohol-exposed mice (P>0.05), but significantly reduced alcohol preference in alcohol-exposed mice (P<0.05). Subsequent analyses showed that Lactobacillus casei significantly ameliorated intestinal, brain tissue, and systemic inflammatory responses in alcohol-exposed mice (P<0.05). 16S rRNA sequencing showed that alcohol-exposed mice treated with Lactobacillus casei exhibited a richer composition of intestinal microorganisms, such as f__Rikenellaceae, g__Alistipes_A_871400, and g__Bacteroides_H genera showed relative enrichment in the High group.
CONCLUSIONS: By showing that Lactobacillus casei slows down alcohol preference and alleviates gut and brain tissue inflammation in alcohol-exposed mice, our findings provide a possible strategy: Lactobacillus casei may be able to serve as a potential target for the prevention and treatment of alcohol dependence.

Chronic endometritis (CE) is common in patients with infertility, and it is challenging to treat with antibiotics as bacteria often acquire resistance to the antibiotics, which leads to frequent recurrence of the condition. Probiotics, especially Lactobacillus species, are known for their usefulness in treating reproductive infections. This study evaluated Lactobacillus crispatus chen 01 (L. crispatus chen 01) isolated from healthy women who were 22-30 years old and married with children. In vitro experiments showed that L. crispatus chen 01 inhibited pathogens and reduced inflammation in CE mice by downregulating inflammatory proteins (TLR, MyD88, and p65/p-p65; L + Abx vs M, P < 0.01), improving histopathological features, and inhibiting bacterial growth. It also regulated endometrial processes, such as enhancing embryo implantation (BMP2 and Wnt4, L + Abx vs M, P < 0.01) via the Wnt/β-catenin pathway, leading to increased pregnancy rates (L + Abx vs M, 100% vs 0%) in mice. In clinical trials, L. crispatus chen 01 improved progesterone levels (P = 0.0038), pregnancy rates (C vs Abx + L. c, 76.19% vs 87.18%), and pathological changes in CE patients. The findings from this study identify the administration of L. crispatus chen 01 as a promising intervention for CE that could improve pregnancy rates.

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.

To study the effect of parecoxib sodium in alleviating inflammation in burned rats and restoring cognitive function in burned rats. 30 SPF grade SD rats were randomly divided into 6 groups: (1) Blank control group (Group C). (2) Sham surgery group (Group Sham). (3) Second-degree burn model (Group B). (4) Low-dose (1 mg/kg/d) parecoxib sodium (Group L+B). (5) Medium-dose (10 mg/kg/d) parecoxib sodium (Group M+B). (6) High-dose (20 mg/kg/d) parecoxib sodium (Group H+B). ELISA measures inflammatory factor IL-2, IL-6, TNF-α and IFN-γ, cognitive function factor NSE, cortisol and S-100β. Combined with water maze and dark avoidance experiments to further verify the recovery of cognitive function in rats. The contents of IL-2, TNF-α and IL-6 in Group M+B were significantly lower than those in Group Sham (P<0.05), and the content of IFN-γ was significantly lower than that in Group Sham (P<0.05). The cognitive markers NSE, S-100β and cortisol levels in Group M+B were significantly higher than those in Group Sham at 2h, 1d, 5d and 10d after operation (P<0.05). In the Group M+B dark-avoidance experiment, the number of probes and errors were not significantly different than those in Group Sham and Group C (P>0.05), and the number of times Group M+B found a platform in the water maze experiment and crossed the platform was second only to Group B and Group C. Parecoxib sodium can effectively reduce inflammation in burn rats and promote cognitive recovery in burn rats, and the optimal dose of parecoxib sodium for burn rats is 10 mg/kg.

BACKGROUND: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia.
OBJECTIVE: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO.
METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR.
RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 μg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment.
CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear.
OBJECTIVE: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.
METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N\'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1β, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3.
RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1β, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1β, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both).
CONCLUSIONS: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.