ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

OBJECTIVE: To preliminarily investigate the effect of buccal acupuncture therapy on ameliorating postoperative pain and enhancing recovery quality among patients undergoing radical resection of gastrointestinal cancers. METHODS: Fifty-two participants were randomized at a 1:1 ratio to either the buccal acupuncture or the control group. The acupuncture protocol entailed targeting 5 predetermined acupoints [CA-2 (Upper jiao), CA-3 (Middle jiao), CA-4 (Lower jiao), CA-6 (back), and CA-7 (waist) and two adjustable acupoints [CA-1 (head) and CA-8 (sacrum)] on each side of the face. The outcomes included the Numeric Rating Scale (NRS) scores for each day within 7 days postoperatively, 15-Item Quality of Recovery Scale (QoR-15) scores, analgesics consumption during and after surgery, incidences of postoperative nausea and vomiting, and perioperative levels of interleukin-6 and glucose. Adverse events related to acupuncture were recorded. RESULTS: Of the initial 52 participants, 46 completed the study and were included in the analysis. Findings indicated that the buccal acupuncture group experienced significantly reduced resting NRS scores in post-anesthesia care unit and throughout the postoperative phase (P=0.001 and P=0.003, respectively), along with enhanced QoR-15 scores on the 3rd postoperative day (P=0.008), compared to the control group. No notable differences were identified in the remaining indicators (P>0.05). CONCLUSION Buccal acupuncture therapy demonstrated significant effectiveness in reducing postoperative pain and improving recovery quality for patients undergoing radical resection of gastrointestinal cancers, presenting a viable intervention without associated adverse outcomes. (Trial registration No. ChiCTR2200060441).
Humans ; Male ; Pilot Projects ; Female ; Acupuncture Therapy/methods* ; Pain, Postoperative/therapy* ; Middle Aged ; Gastrointestinal Neoplasms/surgery* ; Aged ; Acupuncture Points ; Adult

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Intricate and complex interactions between tumor cells and tumor microenvironment(TME)are essential driving factors in tumor development and metastasis.In recent years,modulation of TME to reverse tumor progression has garnered significant attention as a therapeutic strategy.For precise and targeted tumor treatment,there is an urgent need for accurate and effective TME tar-get molecules and relevant prediction model.Fibronectin,a protein with multiple domains in extracellular matrix(ECM),plays a cru-cial role in physiological and pathological processes.Particularly,Fibronectin extra domain B(FN-EDB)in fibronectin is pivotal in regulating interaction between ECM and cells.During active tissue remodeling processes,especially in angiogenesis,FN-EDB expres-sion tends to increase.Studies have indicated that FN-EDB is involved in regulating various key aspects of tumorigenesis,including promoting tumor cell invasion and metastasis,influencing development of immune evasion mechanisms,enhancing tumor angiogene-sis,and contributing to development of chemoresistance.Therefore,targeting FN-EDB as a potential therapeutic target for cancer treat-ment and developing relevant therapeutic drugs hold significant importance and promising clinical prospects.This article reviews roles of FN-EDB in TME in recent years and research progress on tumor immunotherapy targeting this molecule,with aim of providing new insights and strategies for cancer treatment.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.