Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

BACKGROUND

Post-ERCP pancreatitis (PEP) remains the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). Rectal indomethacin is one of the recommended medications given to prevent pancreatitis in high-risk patients undergoing ERCP.

This study aims to evaluate the effectiveness of diclofenac in preventing PEP, to compare its different routes of administration, and to determine the severity of pancreatitis in patients who develop PEP.

Databases from PubMed, ScienceDirect and COCHRANE Library were searched for randomized controlled trials (RCTs) comparing diclofenac with placebo in the prevention of PEPup to August 2020. Risk ratio at 95% Confidence Intervals (CI) were calculated to evaluate the incidence of the interested outcomes.

Eleven RCTs with a total population of 2,012 were reviewed in this study. Diclofenac was associated with a significant reduction in overall risk of PEP compared with patients with placebo (RR = 0.59; 95%, 0.47 0.74; P < 0.000001), with a mild heterogeneity (P = 0.05; I2 = 41%). Subgroup analyses showed that rectal diclofenac was the superior choice to significantly reduce the overall incidence of PEP(RR = 0.34; 95%, 0.23-0.51; P < 0.000001).

Rectal diclofenac significantly reduces the risk of PEPand therefore, should be recommended as routine for clinical use in adult patients who will undergo ERCP.

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Antirheumatic Agents/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.
Humans ; Drug Delivery Systems ; Administration, Cutaneous ; Pharmaceutical Preparations ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Needles

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.
Plant Extracts/pharmacology* ; Asteraceae ; Triterpenes ; Sesquiterpenes/pharmacology* ; Anti-Inflammatory Agents ; Phytochemicals/pharmacology*

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.
Animals ; Mice ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/pharmacology* ; Interleukin-1beta/genetics* ; Mice, Inbred C57BL

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC₅₀ value of 8.77 μmol·L^-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.
Tripterygium/chemistry* ; Esters/pharmacology* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/chemistry* ; Nitric Oxide/analysis* ; Sesquiterpenes/chemistry* ; Molecular Structure

Aims: This study was aimed to investigate the anti-inflammatory and anti-rheumatoid effects of the Bacillus amyloliquefaciens derived surfactin. Methodology and results: Crude and biosurfactant extracts were analyzed using thin-layer chromatography to determine the presence of biosurfactant. Both extracts were evaluated for their inhibitory effects against the acetylcholinesterase and 5-lipoxygenase enzymes. Human synovial cells were induced with TNF-α and IL-1β. The percentages of the cell viability for both normal and induced cells were determined with an MTT assay. Results showed that surfactin was detected in the biosurfactant extract and demonstrated higher inhibitory effects compared to the crude extract against both inhibitory enzymes acetylcholinesterse (IC50=30.60 μg/mL) and lipoxygenase (IC50=110.10 μg/mL). Both crudes showed no cytotoxic effects at the highest concentration used (50 μg/mL) against normal human synovial cells but showed active reactions against the induced cells. The anti-proliferative effects of biosurfactant and crude extracts were in dose-dependent manner. Conclusion, significance and impact of study Notably, surfactin obtained from B. amyloliquefaciens has shown an inhibitory effect against pro-inflammatory enzymes and cell viability of the induced rheumatoid arthritis cell line. These results highlighted the therapeutic potential of surfactin application as an anti-inflammatory agent for arthritis treatment. Further study is needed to elucidate the mechanisms underlying the anti-inflammatory effect of surfactin.
Bacillus amyloliquefaciens ; Surface-Active Agents ; Anti-Inflammatory Agents ; Rheumatoid Factor

To develop antimicrobials against Staphylococcus aureus by high throughput screening of drug library. The type of this study is experimental research. The clinical isolates of S. aureus were collected from the sputum samples of respiratory inpatient department of the Third Xiangya Hospital of Central South University. The anti-planktonic cells growth inhibition activity of FDA-approved drugs library (including 1 573 molecules) was assessed by building a planktonic cells screening platform; The biofilm inhibitory effect of the FDA-approved drugs was detected by building a biofilm screening platform combined with crystal violet staining; Minimal inhibitory concentrations of the selected hits were determined by broth microdilution assay. Finally, the cytotoxicity of the selected hits was detected by CCK-8 assay. The results showed that 218 hits were exhibited effective growth inhibitory effects against S. aureus by setting the concentrations of the molecules in the FDA-approved library to 100 μmol/L. These selected molecules are mainly anti-infective drugs, accounting for 118 hits; Followed by anti-cancer drugs, anti-inflammatory/-immune drugs, neurological drugs, cardiovascular drugs, endocrine drugs, and metabolic disease drugs, which accounts for 40, 19, 12, 9, 8, and 3 hits; Other unclassified drugs accounts for 9 hits. The top 10 hits exhibiting anti-planktonic cells activity against S. aureus were mainly including antitumor drugs, followed by neurological drugs and unclassified drugs like vitamin K3 with the inhibition rate of 99.65%-100%. Similarly, the top 10 hits showing biofilm inhibitory effects against S. aureus were also mainly including antitumor drugs, followed by neurological drugs and anti-inflammatory/-immune drugs with the inhibition rate of 50.22%-92.95%. The minimal inhibitory concentration (MIC) of the 51 hits by second round screening was determined by micro-dilution assay, which mainly include the antitumor drugs, cardiovascular drugs, endocrine drugs, anti-inflammatory/-immune drugs, metabolic disease drugs, neurological drugs and other unclassified drugs accounted for 22, 5, 3, 9, 2, 5 and 5 hits, respectively, with the MICs of 1.56-50 μmol/L, 6.25-25 μmol/L, 6.25-25 μmol/L, 0.2-50 μmol/L, 25-50 μmol/L, 1.56-50 μmol/L and 0.1-12.5 μmol/L, respectively. In conclusion, the minimum inhibitory concentrations of small molecules screened through high-throughput assay are at the level of micromolar with strong drug development potential and high modifiability. The high effective anti-planktonic cells and anti-biofilm activity by these molecules are expected to provide new ideas for the development of new antimicrobials against S. aureus.
Humans ; Staphylococcus aureus ; Anti-Bacterial Agents/pharmacology* ; High-Throughput Screening Assays ; Staphylococcal Infections ; Anti-Infective Agents/pharmacology* ; Microbial Sensitivity Tests ; Biofilms ; Antineoplastic Agents/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Cardiovascular Agents/pharmacology* ; Metabolic Diseases