An integrative pharmacology-based study on the efficacy and mechanism of essential oil of Chaihu Guizhi Decoction on influenza A virus induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND 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.

Effect of inflammatory factors on myocardial infarction.

BACKGROUND: Cohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear. METHODS AND RESULTS: By utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.00-1.17; p = 0.04). C-reactive protein levels correlated positively with MI. No associations were observed with IL-1 beta, IL-6, IL-18, procalcitonin, TNF-α, total white cell count, or neutrophil percentage of white cells. Neutrophil count and C-reactive protein were inversely associated with lactate dehydrogenase: neutrophil cell count (OR 0.95; 95% CI, 0.93-0.98; p < 0.01) and C-reactive protein (OR 0.96; 95% CI, 0.92-1.00; p = 0.02). No associations of MI with myoglobin, troponin I, and creatine kinase-MB levels were found. CONCLUSIONS: This two-sample MR analysis revealed a causal positive association of MI with neutrophil count, C-reactive protein level, and the myocardial injury marker lactate dehydrogenase. These results indicate that monitoring C-reactive protein and neutrophil counts may be useful in management of MI patients.

Immune cells mediate the causal pathway linking circulating complements to cancer: A Mendelian randomization study.

BACKGROUND: The role of complement in cancer remains controversial. Whether immune cells and inflammatory factors mediate the pathway from complement to cancer has not been fully elucidated. METHODS: We conducted bidirectional Mendelian randomization (MR) analysis to explore the causal association between complement components and cancer. Meta-analysis was conducted to enhance the robustness of the results. We further explored the mediation roles of immune cells and inflammatory factors in these associations. RESULTS: Our study identified causal associations between 11 complement components and 12 types of cancer. Furthermore, we identified five immune cells as potential mediators: BAFF-R on IgD + CD38- naive B cell mediated 7.434% of the increased risk for liver cancer from C3; CD4 on CD39 + activated CD4 regulatory T cell mediated 12.384% of the increased risk for biliary tract cancer from CD93; CD25 + + CD45RA + CD4 not regulatory T cell and Basophil %CD33dim HLA DR- CD66b- mediated 7.721% and 7.986% of the increased risk of colorectal cancer from MASP1, respectively; CD45RA on resting CD4 regulatory T cell mediated 11.444% of the increased risk of skin cancer from MASP1. CONCLUSION: This study revealed the causal relationships between complement components and certain cancers, with five immune cells as potential mediators.

Clinical Efficacy and Mechanistic Insights of Anshen Dingzhi Prescription on Breast Cancer-Related PTSD Through Network Pharmacology and Molecular Docking.

Anshen Dingzhi prescription (ADP) is a classic prescription of traditional Chinese medicine, which has been used in the treatment of neuropsychiatric diseases. However, its treatment of breast cancer-related post-traumatic stress disorder (BC-PTSD) lacks clinical research evidence and its mechanism is not clear. The present study investigated the efficacy and action mechanism of ADP against BC-PTSD. The results of the clinical trial showed that after 4 weeks of treatment, both groups showed reduced post-traumatic stress disorder checklist-civilian version (PCL-C), Pittsburgh sleep quality index (PSQI), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores, and increased functional assessment of cancer therapy-breast (FACT-B) scores. The serum cortisol (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels were decreased and brain-derived neurotrophic factor (BDNF) level were increased, and the improvement of serum TNF-α, IL-1ß, and BDNF in treatment group was better than that of the control group. The overall treatment efficacy in the treatment group (43.90%) was superior to that in the control group (23.81%), and the overall incidence of adverse effects was lower than that in the control group. The results of network analysis and molecular docking showed that ADP blood components could act on IL1B, TNF, and BDNF. ADP contributes to the treatment of BC-PTSD symptoms, with a mechanism possibly related to its regulatory effect on TNF-α, IL-1ß, and BDNF levels.Trial registration: Chinese Clinical Trial Registry, http://www.chictr.org.cn,ChiCTR2300077801.

Clinical Effect of Norepinephrine Combined with Esmolol Treatment in Patients with Septic Shock and Its Impact on Prognosis.

Objective: To unveil the influence of norepinephrine (NE) combined with esmolol treatment on cardiac function, hemodynamics, inflammatory factor levels, and prognosis in patients with septic shock. Methods: Ninety-six patients with septic shock admitted to our hospital from January 2021 to June 2023 were retrospectively analyzed and divided into the control and observation groups according to the different treatment methods. The control group was treated with standard anti-infection and fluid resuscitation, followed by NE administration [with an infusion rate of 0.1-0.5 µg/(kg-min)]. The observation group was treated with esmolol [starting pumping rate of 50 µg/(kg-min) and adjusting the pumping rate according to the target heart rate] in combination with the control group. Changes in hemodynamic parameters, including heart rate, mean arterial pressure, central venous pressure, cardiac index, stroke volume index, and systemic vascular resistance index, were monitored by pulse-indicating continuous cardiac output monitors before treatment (T0), 24h after treatment (T1), and 72h after treatment (T2); changes in cardiac function before and after 72h of treatment, indicators of inflammatory factors before and after treatment, and indicators of oxygenation metabolism were assessed; and adverse drug reactions during treatment were recorded in both groups. Results: NE combined with esmolol treatment improved the efficacy of patients with septic shock; was beneficial for the enhancement of blood perfusion in patients; improved the patient's cardiac function, reduced myocardial injury, and suppressed the inflammatory response in patients; improved the oxygenation metabolism and the prognosis of patients; did not significantly increase the adverse drug reactions of patients and had a better safety profile. Conclusion: NE combined with esmolol treatment can improve the efficacy of patients with septic shock, improve their cardiac function and hemodynamic indices, reduce myocardial injury and inflammatory response, and have a better safety profile, which is conducive to improving patient prognosis and reducing mortality.

Aldosterone promotes calcification of vascular smooth muscle cells in mice through the AIF-1/Wnt/ß-catenin signaling pathway.

OBJECTIVE: This study aimed to investigate the impact of aldosterone on calcification in murine vascular smooth muscle cells (VSMCs) via the allograft inflammatory factor-1 (AIF-1)/Wnt/ß-catenin signaling pathway. METHODS: Mouse VSMCs were cultured in vitro, and calcification was induced by treatment with 100 nM aldosterone. The level of calcification in mouse VSMCs was evaluated using colorimetric assays to assess ALP activity and qRT-PCR to identify the expression of calcification-related markers, such as Runx2, α-SMA, OCN, and ALP mRNA. Western blot analysis was performed to determine the protein expression levels associated with the Wnt/ß-catenin pathway (LRP6, p-LRP6, GSK3ß, p-GSK3ß, ß-catenin) and AIF-1. Plasmid transfection techniques were utilized to either knock down or overexpress AIF-1, and the subsequent alterations in these markers were observed. RESULTS: (1) Compared to the control group, the aldosterone treatment group with exhibited a significant increase in ALP. Concurrently, Runx2, OCN, and ALP mRNA levels increased, as did LRP6, p-LRP6, GSK3ß, p-GSK3ß, ß-catenin, and AIF-1 protein levels. Additionally, a significant decrease in the expression of α-SMA mRNA was observed (P < 0.05). (2) The aldosterone + oe-AIF-1 group showed significant increases in ALP activity compared to the aldosterone + oe-NC group, whereas the aldosterone + sh-AIF-1 group showed significant decreases (P < 0.05). (3) The aldosterone + oe-AIF-1 group exhibited significantly upregulated expression of AIF-1, p-LRP6/LRP6, p-GSK3ß/GSK3ß, and ß-catenin proteins relative to the aldosterone + oe-NC group (P < 0.05). This was concurrent with increased mRNA expression of Runx2, OCN, and ALP, and decreased α-SMA mRNA expression (P < 0.05). CONCLUSION: Aldosterone affects the calcification process in mouse VSMCs, and the activation of the AIF-1/Wnt/ß-catenin signaling pathway is the mechanism behind its action.

The causality between smoking and intervertebral disc degeneration mediated by IL-1ß secreted by macrophage: A Mendelian randomization study.

There is still a lack of high-level evidence regarding the causal relationship between smoking and intervertebral disc degenerative diseases. This study utilized data from genome wide analysis studies and conducted two-sample Mendelian randomization analyses across multiple heterogeneous datasets. We evaluated the causal relationships between smoking behavior, serum inflammatory factors, serum chemokines, and intervertebral disc degeneration. Sensitivity analysis was performed to examine data heterogeneity and the pleiotropy of causal effects. The results indicated that smokers were liable to develop intervertebral disc degeneration (OR 1.770; 95 % CI, 1.519-2.064; p = 2.992 × 10-13), and long-term smoking behavior increased the risk of intervertebral disc degeneration (OR 1.715; 95 % CI 1.475-1.994; P = 2.220 × 10-12). Additionally, a causal relationship was confirmed between serum IL-1ß level and intervertebral disc degeneration (OR 1.087; 95 % CI, 1.023-1.154; p = 0.007). The "smoking index" representing lifelong smoking habit was also found to be causally related to serum MCP-3 level(ß = 0.292; SE = 0.093; p = 0.002). All of the causality mentioned above remained stable in sensitivity tests. Based on the analysis results and fundamental medicine theories around macrophage-induced inflammation in degenerative intervertebral discs, we have constructed a new mechanism that long-term smoking could induce an increase in serum MCP-3 level, promoting the gathering and activation of monocyte macrophages. Furthermore, the recruited macrophages led to an increase in local IL-1ß within the intervertebral disc, ultimately exacerbating the process of intervertebral disc degeneration. What we have found is expected to accelerate the development of prevention and treatment of intervertebral disc degeneration.

Studies on the Preparation of a Microemulsion Formulation of Matricaria Recutita Essential Oil and the Treatment of 2,4-Dinitro-Chlorobenzene- Induced Eczema in Mice by Inhibiting Inflammation.

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. CONCLUSION: The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

Exosomal Drug Delivery Systems: A Novel Therapy Targeting PD-1 in Septic-ALI.

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-1ß 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. CONCLUSION: In both in vitro and in vivo settings, MEP demonstrates superior therapeutic efficacy compared to individual components in the context of septic-ALI.

Role and mechanism of Lactobacillus casei in the modulation of alcohol preference in mice.

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. CONCLUSION: 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.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway.

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. AIM: 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-1ß, 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-1ß, 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-1ß, 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). CONCLUSION: 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.

Pathogenicity characteristics of different subgenotype pseudorabies virus in newborn piglets.

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.

Effects of parecoxib sodium on early cognitive impairment and inflammation levels in burned rats.

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-100ß. 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-100ß 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.

[Research progress of type 2 inflammation-related tissue remodeling in nasal polyps].

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.

The Therapeutic Potential of Lactobacillus crispatus for Chronic Endometritis: A Comprehensive Clinical Trial and Experimental Investigation.

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/ß-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.

Endothelial Cell Dysfunction Due to Molecules Secreted by Macrophages in Sepsis.

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.

LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes.

Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the interaction of lincRNA-p21/AIF-1/CMPK2/NLRP3 via exosomes in urate nephropathy. This study evaluated the effect of lincRNA-p21/AIF-1/CMPK2/NLRP3 using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. In clinical research section, the level of lincRNA-p21/AIF-1 in exosomes of urine in patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the level of exosomes, inflammation, autophagy, and apoptosis was increased in HK2 cells induced by urate. Additionally, the expression of lincRNA-p21, AIF-1, CMPK2, and NLRP3 was upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors regulated the level of inflammation, autophagy, and apoptosis in HK2 cells. In conclusion, the pathway of lincRNA-p21/AIF-1/CMPK2/NLRP3 contributed to inflammation, autophagy, and apoptosis of human renal tubular epithelial cell induced by urate via exosomes. Additionally, the specific exosomes in urine might serve as novel biomarkers for urate nephropathy.

Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1ß in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.

Antidepressant advantage of Chaihushugan san in female mice: A novel signaling mechanism in hippocampus.

ETHNOPHARMACOLOGICAL RELEVANCY: Chaihushugan san (CSS), a classic formula for soothing the liver and relieving depression, has been identified to produce rapid antidepressant-like effects in female mice. However, the gender predominance and underlying mechanisms of CSS's antidepressant remain unclear. AIM OF THE STUDY: In this study, we focused on unraveling the gender predominance of CSS in antidepressant and the specific neuronal mechanisms that mediate this predominance. METHODS AND MATERIALS: Tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT) were used to evaluate depressive phenotypes or antidepressant-like effects of CSS in female and male chronic unpredictable mild stress (CUMS) mice model. RNA-sequencing was used to screen specific target for CSS antidepressant gender dominance. RT-PCR and elisa were used to detect the expressions of specific molecule, hormones, and inflammatory factors in the hippocampus. hippocampal viral overactivation and pharmacological blockade were used to detect the correlation between CSS antidepressant gender dominance and related targets. RESULTS: In the present study, both female and male mice displayed depressive phenotypes including significant increasing immobility time in TST and reducing sucrose preference ratio in SPT after exposing CUMS for 3 weeks. However, acute administration of CSS (2, 4 g/kg) improved the depressive phenotypes only in female mice or not male mice at 2 h later. Moreover, the expressions of TC2N were increased only in female mice after exposing CUMS for 3 weeks, which were also reversed by CSS after a single administration 2 h later, but no alterations in male mice. The hippocampal expressions of estrogen receptor ß (Erß), pro-inflammatory factors (IL-1ß and TNF-α) and anti-inflammatory factors (IL-10, TGF-ß and IL-1Rα) were all abnormal in female CUMS mice model, which were all normalized by CSS. Furthermore, overactivation of hippocampal TC2N by AAV-TC2N+/+ blocked the antidepressant-like effects of CSS and the up-regulation of hippocampal Erß in female mice. However, inhibition of Erß blunted the antidepressant-like effects of CSS and CSS's suppression of pro-inflammatory factors (IL-1ß and TNF-α), which had no any effect on hippocampal TC2N and anti-inflammatory factors (IL-10 and TGF-ß). CONCLUSIONS: The study revealed that CSS had antidepressant superiority in female mice depending on inhibiting hippocampal TC2N and then activating Erß, further inhibiting the release of pro-inflammatory factors to produce antidepressant effects, which provided a basis for the guidance of CSS in clinical application, new ideas and targets for the development of drugs for depression with gender differences.

Clinical therapeutic effect of self-prescribed Sanhanchushi Tongbi on lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) commonly occurs during spinal surgery; LDH is on the increase in younger patients and is classified as "paralysis" and "back pain." Sanhanchushi Tongbi (SPST) is a customized prescription. It disperses cold, relieves pain, removes cold from the meridians and viscera, and treats neuropathic pain. However, few studies have investigated its mechanism of pain relief. AIM: To observe the clinical therapeutic effects on LDH treated with self-prescribed SPST. METHODS: A total of 211 patients with LDH syndrome were divided into two groups: 107 patients in the control group were treated with conventional massage combined with traction, and 104 patients in the observation group were treated with a combination of the control regimen and self-prescribed oral SPST. The patients were treated for 4 wk. Indices of traditional Chinese medicine (TCM) syndrome score and serum inflammatory factor levels were measured. RESULTS: After therapy, the TCM syndrome score in the observation group was significantly lower than that in the control group (P < 0.05). The main symptoms, clinical signs, daily activities, and Japanese Orthopedic Association scores in the observation group were significantly higher than those in the control group after therapy (P < 0.05). The levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein were lower in the observation group than in the control group (P < 0.05). In the observation group, superoxide dismutase levels were significantly higher, whereas malondialdehyde levels were significantly lower, compared with the control group (P < 0.05). The overall efficacy rate in the observation group was 96.15%, which was substantially higher than that in the control group (88.79%; P < 0.05). CONCLUSION: Self-prescribed SPST can reduce the levels of inflammatory and pain-causing factors as well as lumbar pain in patients with LDH.