Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

The Glycine soja cytochrome P450 gene GsCYP82C4 confers alkaline tolerance by promoting reactive oxygen species scavenging.

Recent studies have demonstrated the crucial role of Cytochrome P450 enzymes (CYPs) in the production of secondary metabolites, phytohormones and antioxidants in plants. However, their functional characterization specifically under alkaline stress remains elusive. CYP82C4 was the key gene screened from a family of wild soybean CYPs in our previous studies. The aim of this present study was to clone the Glycine soja GsCYP82C4 gene and characterize its functions in Arabidopsis and Glycine max. The results showed that the GsCYP82C4 gene displayed a high expression in different plant tissues at mature stages compared to young stages. Further, higher temporal expression of the GsCYP82C4 gene was noted at 6, 12 and 24 h time points after alkali treatment in leaves compared to roots. In addition, overexpression of GsCYP82C4 improved alkaline stress tolerance in Arabidopsis via increased root lengths and fresh biomass and strengthened the antioxidant defense system via a reduction in superoxide radicals in transgenic lines compared to wild type (WT) and atcyp82c4 mutants. Further, the expression levels of stress-related marker genes were up-regulated in GsCYP82C4 OX lines under alkali stress. The functional analysis of GsCYP82C4 overexpression in soybean displayed better hairy root growth, increased fresh weight, higher antioxidant enzyme activities and reduced lipid peroxidation rates in OX lines compared to the soybean WT (K599) line. In total, our study displayed positive roles of GsCYP82C4 overexpression in both Arabidopsis and Glycine max to alleviate alkaline stress via altering expression abundance of stress responsive genes, stronger roots, higher antioxidant enzyme activities as well as reduced rates of lipid peroxidation and superoxide radicals.

Cytoplasmic localization of SETDB1­induced Warburg effect via c­MYC­LDHA axis enhances migration and invasion in breast carcinoma.

SET domain bifurcated 1 (SETDB1), a pivotal histone lysine methyltransferase, is transported to the cytoplasm via a chromosome region maintenance 1 (CMR1)­dependent pathway, contributing to non­histone methylation. However, the function and underlying mechanism of cytoplasmic SETDB1 in breast cancer remain elusive. In the present study, immunohistochemistry revealed that elevated cytoplasmic SETDB1 was correlated with lymph node metastasis and more aggressive breast cancer subtypes. Functionally, wound healing and Transwell assays showed that cytoplasmic SETDB1 is key for cell migration and invasion, as well as induction of epithelial­mesenchymal transition (EMT), which was reversed by leptomycin B (LMB, a CMR1 inhibitor) treatment. Furthermore, RNA­seq and metabolite detection revealed that cytoplasmic SETDB1 was associated with metabolism pathway and elevated levels of metabolites involved in the Warburg effect, including glucose, pyruvate, lactate and ATP. Immunoblotting and reverse transcription­quantitative PCR verified that elevation of cytoplasmic SETDB1 contributed to elevation of c­MYC expression and subsequent upregulation of lactate dehydrogenase A (LDHA) expression. Notably, gain­ and loss­of­function approaches revealed that LDHA overexpression in T47D cells enhanced migration and invasion by inducing EMT, while its depletion in SETDB1­overexpressing MCF7 cells reversed SETDB1­induced migration and invasion, as well as the Warburg effect and EMT. In conclusion, subcellular localization of cytoplasmic SETDB1 may be a pivotal factor in breast cancer progression. The present study offers valuable insight into the novel functions and mechanisms of cytoplasmic SETDB1.

Overexpression of cucumber CYP82D47 enhances resistance to powdery mildew and Fusarium oxysporum f. sp. cucumerinum.

Cytochrome P450s are a large family of protein-encoding genes in plant genomes, many of which have not yet been comprehensively characterized. Here, a novel P450 gene, CYP82D47, was isolated and functionally characterized from cucumber (Cucumis sativus L.). Quantitative real-time reverse-transcription polymerase chain reaction analysis revealed that CYP82D47 expression was triggered by salicylic acid (SA) and ethephon (ETH). Expression analysis revealed a correlation between CYP82D47 transcript levels and plant defense responses against powdery mildew (PM) and Fusarium oxysporum f. sp. cucumerinum (Foc). Although no significant differences were observed in disease resistance between CYP82D47-RNAi and wild-type cucumber, overexpression (OE) of CYP82D47 enhanced PM and Foc resistance in cucumber. Furthermore, the expression levels of SA-related genes (PR1, PR2, PR4, and PR5) increased in CYP82D47-overexpressing plants 7 days post fungal inoculation. The levels of ETH-related genes (EIN3 and EBF2) were similarly upregulated. The observed enhanced resistance was associated with the upregulation of SA/ETH-signaling-dependent defense genes. These findings indicate the crucial role of CYP82D47 in pathogen defense in cucumber. CYP82D47-overexpressing cucumber plants exhibited heightened susceptibility to both diseases. The study results offer important insights that could aid in the development of disease-resistant cucumber cultivars and elucidate the molecular mechanisms associated with the functions of CYP82D47.

A comprehensive study of oxidative stress-related effects on the prognosis and drug therapy of cervical cancer.

BACKGROUND: Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS-related genes in CC. METHODS: The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS-related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS-related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single-sample GSEA (ssGSEA) techniques. RESULTS: The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS-related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high- and low-risk groups, with the low-risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group. CONCLUSIONS: A new model was constructed based on eight OS-related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

The recovery of the microbial community after plaque removal depends on periodontal health status.

Plaque accumulation and microbial community changes are important causes of periodontal disease. Cleaned plaque microorganisms will reattach to form biofilms, but the recovery and outcome of plaque microbial communities in different periodontal health states remain unknown. In this study, we tracked the biofilm remodeling process in 206 dental plaque samples from 40 healthy periodontal, gingivitis and periodontitis volunteers at 6 time points before and after supragingival scaling. We found that microbial communities of different periodontal states changed asynchronously during the process, and the more severe the periodontal disease condition, the more lagged the recovery of plaque microorganisms to their original state after cleaning; this reflected a higher degree of plaque development in periodontitis samples. The plaque index and bleeding index were significantly correlated with plaque recovery, especially the recovery of bacteria such as Abiotrophia and Capnocytophaga. Meanwhile, we found that the microbial community structure of different periodontal health states was most similar at the Day 3 after plaque cleaning, and the communities gradually differentiated and developed in different directions. Abiotrophia and other bacteria might play an important role in determining the development trend of plaque biofilms. The discovery of specific time points and bacteria was of great value in clarifying the pathogenesis of periodontal disease and in seeking targets for prevention and treatment.

DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway.

CDK4/6 are important regulators of cell cycle and their inhibitors have been approved as anti-cancer drugs. Here, we report a STING-dependent anti-tumor immune mechanism responsible for tumor suppression by CDK4/6 blockade. Clinical datasets show that in human tissues, CDK4 and CDK6 are over-expressed and their expressions are negatively correlated with patients' overall survival and T cell infiltration. Deletion of Cdk4 or Cdk6 in tumor cells significantly reduce tumor growth. Mechanistically, we find that Cdk4 or Cdk6 deficiency contributes to an increased level of endogenous DNA damage, which triggers the cGAS-STING signaling pathway to activate type I interferon response. Knockout of Sting is sufficient to reverse and partially reverse the anti-tumor effect of Cdk4 and Cdk6 deficiency respectively. Therefore, our findings suggest that CDK4/6 inhibitors may enhance anti-tumor immunity through the STING-dependent type I interferon response.

Derepressing of STAT3 and USP7 contributes to resistance of DLBCL to EZH2 inhibition.

Diffuse large B-cell lymphoma is the most common subtype of lymphoma, representing ∼25 % of non-Hodgkin lymphoid malignancies. EZH2 is highly expressed in Diffuse large B-cell lymphoma and ∼22 % of patients contain EZH2 mutations. EZH2 have been studied as a potential therapeutic target for a decade, but efficient inhibition of EZH2 did not robustly kill lymphoma cells. Here, we found that EZH2 mediates repression of oncogenic genes STAT3 and USP7 in Diffuse large B-cell lymphoma cells. Inhibition of EZH2 leads to upregulation of STAT3 and USP7 at both RNA and protein levels. Along with USP7 upregulation, MDM2 is upregulated and its ubiquitylation substrate, Tumor suppressor P53, is downregulated. Upregulation of STAT3 and downregulation of p53 can strength cell proliferation and prevent cells from apoptosis, which suggests resistance mechanisms by which cells survive EZH2 inhibition-induced cell death. Short-course co-inhibition of USP7 and EZH2 showed increased apoptosis and cell proliferation prevention with the concentration as low as 0.08 µM. In STAT3 and USP7 depleted cells, EZH2 inhibition shows superior efficacy of apoptosis, and in EZH2 depleted cells, USP7 inhibition also shows superior efficacy of apoptosis. Thus, our findings suggest a new precision therapy by combinational inhibition of EZH2 with STAT3 or USP7 for Diffuse large B-cell lymphoma.

UDP-glycosyltransferase gene SlUGT73C1 from Solanum lycopersicum regulates salt and drought tolerance in Arabidopsis thaliana L.

Among abiotic stresses, plants are the most vulnerable to salt and drought stresses. These stresses affect plant growth and development. Glycosyltransferases are involved in the responses of plants to abiotic stresses. In this study, a UDP-glycosyltransferase gene (SlUGT73C1) from Solanum lycopersicum was isolated and identified, which exhibited induction under salt or drought stress. The full length of SlUGT73C1 was 1485 bp, encoding 494 amino acids. Stress-related cis-acting elements were present in the promoter sequence of SlUGT73C1, such as ARE, LTR, and GC motifs. Compared with the wild-type plants, Arabidopsis thaliana overexpressing SlUGT73C1 exhibited increased seed germination rate and SOD and POD activities, decreased MDA content, and increased expression levels of osmotic stress regulators genes, rate-limiting enzymes genes in the proline synthesis pathway, Na+/K+ reverse transporter genes, and rate-limiting genes in the ABA biosynthesis pathway under salt or drought stress. These results indicated that SlUGT73C1 plays an important role in regulating salt and drought tolerance in plants.

GsPKS24, a calcineurin B-like protein-interacting protein kinase gene from Glycine soja, positively regulates tolerance to pH stress and ABA signal transduction.

SOS2-like protein kinases (PKS/CIPK) family genes are known to be involved in various abiotic stresses in plants. Even though, its functions have been well characterized under salt and drought stresses. The roles of PKS genes associated with alkaline stress response are not fully established yet. In this study, we identified 56 PKS family genes which could be mainly classified into three groups in wild soybean (Glycine soja). PKS family genes transcript profiles revealed different expression patterns under alkali stress. Furthermore, we confirmed the regulatory roles of GsPKS24 in response to NaHCO3, pH and ABA treatments. Overexpression of GsPKS24 enhanced plant tolerance to pH stress in Arabidopsis and soybean hairy roots but conferred suppressed pH tolerance in Arabidopsis atpks mutant. Additionally, Overexpression of GsPKS24 decreased the ABA sensitivity compared to Arabidopsis atpks mutant which displayed more sensitivity towards ABA. Moreover, upregulated expression of stress responsive and ABA signal-related genes were detected in GsPKS24 overexpression lines. In conclusion, we identified the wild soybean PKS family genes, and explored the roles of GsPKS24 in positive response to pH stress tolerance, and in alleviation of ABA sensitivity.

Corrigendum: Advancements in understanding the molecular and immune mechanisms of Bartonella pathogenicity.

[This corrects the article DOI: 10.3389/fmicb.2023.1196700.].

Strigolactone signaling gene from soybean GmMAX2a enhances the drought and salt-alkaline resistance in Arabidopsis via regulating transcriptional profiles of stress-related genes.

Strigolactone (SL) is a new plant hormone, which not only plays an important role in stimulating seed germination, plant branching, and regulating root development, but also plays an important role in the response of plants to abiotic stresses. In this study, the full-length cDNA of a soybean SL signal transduction gene (GmMAX2a) was isolated, cloned and revealed an important role in abiotic stress responses. Tissue-specific expression analysis by qRT-PCR indicated that GmMAX2a was expressed in all tissues of soybean, but highest expression was detected in seedling stems. Moreover, upregulation of GmMAX2a transcript expression under salt, alkali, and drought conditions were noted at different time points in soybean leaves compared to roots. Additionally, histochemical GUS staining studies revealed the deep staining in PGmMAX2a: GUS transgenic lines compared to WT indicating active involvement of GmMAX2a promoter region to stress responses. To further investigate the function of GmMAX2a gene in transgenic Arabidopsis, Petri-plate experiments were performed and GmMAX2a OX lines appeared with longer roots and improved fresh biomass compared to WT plants to NaCl, NaHCO3, and mannitol supplementation. Furthermore, the expression of several stress-related genes such as RD29B, SOS1, NXH1, AtRD22, KIN1, COR15A, RD29A, COR47, H+-APase, NADP-ME, NCED3, and P5CS were significantly high in GmMAX2a OX plants after stress treatment compared to WT plants. In conclusion, GmMAX2a improves soybean tolerance towards abiotic stresses (salt, alkali, and drought). Hence, GmMAX2a can be considered a candidate gene for transgenic breeding against various abiotic stresses in plants.

Advancements in understanding the molecular and immune mechanisms of Bartonella pathogenicity.

Bartonellae are considered to be emerging opportunistic pathogens. The bacteria are transmitted by blood-sucking arthropods, and their hosts are a wide range of mammals including humans. After a protective barrier breach in mammals, Bartonella colonizes endothelial cells (ECs), enters the bloodstream, and infects erythrocytes. Current research primarily focuses on investigating the interaction between Bartonella and ECs and erythrocytes, with recent attention also paid to immune-related aspects. Various molecules related to Bartonella's pathogenicity have been identified. The present review aims to provide a comprehensive overview of the newly described molecular and immune responses associated with Bartonella's pathogenicity.

Synergistic effects of combined treatment of 1,2-dichloroethane and high-dose ethanol on liver damage in mice and the related mechanisms.

Our previous studies have shown that the metabolism of 1,2-dichloroethane (1,2-DCE) mediated by CYP2E1 could result in oxidative damage in the liver of mice. In the current study, we further investigated the effects of combined treatment with 1,2-DCE and high dose ethanol on liver and the mechanisms since both of them can be metabolized by CYP2E1 in the liver. There are several novel findings in the current study. First, combined treatment of mice with 1,2-DCE and high-dose ethanol could synergistically upregulate both protein and mRNA levels of CYP2E1, which might aggravate liver damage through CYP2E1-mediated oxidative stress. Second, the combined treatment could also synergistically trigger NLRP3 inflammasome activation and inflammatory responses in the liver. Third, the combined treatment synergistically upregulated the antioxidant defence systems in response to oxidative stress, however the compensatory mechanisms of antioxidant defence systems appeared to be insufficient to protect liver damage in the mice. Finally, the upregulated CYP2E1 expression was confirmed by using its specific inhibitor to play the crucial roles in liver damage in the mice during the combined treatment.

SLs signal transduction gene CsMAX2 of cucumber positively regulated to salt, drought and ABA stress in Arabidopsis thaliana L.

Recent studies have demonstrated that strigolactones (SLs) participate in the regulation of stress adaptation, however, the mechanisms remain elusive. MAX2 (MORE AXILLARY GROWTH2) is the key gene in the signal transduction pathway of SLs. This study aimed to clone and functionally characterize the CsMAX2 gene of cucumber in Arabidopsis. The results showed that the expression levels of the CsMAX2 gene changed significantly after salt, drought, and ABA stresses in cucumber. Moreover, the overexpression of CsMAX2 promoted stress tolerance and increased the germination rate and root length of Arabidopsis thaliana. Meanwhile, the content of chlorophyll increased and malondialdehyde decreased in CsMAX2 OE lines under salt and drought stresses. Additionally, the expression levels of stress-related marker genes, especially AREB1 and COR15A, were significantly upregulated under salt stress, while the expression levels of all genes were upregulated under drought stress, except ABI4 and ABI5 genes. The level of NCED3 continued to rise under both salt and drought stresses. In addition, D10 and D27 gene expression level also showed a continuous increase under ABA stress. The result suggested the interaction between SL and ABA in the process of adapting to stress. Overall, CsMAX2 could positively regulate salt, drought, and ABA stress resistance, and this process correlated with ABA transduction.

Sodium Butyrate Ameliorates Fluorosis-Induced Neurotoxicity by Regulating Hippocampal Glycolysis In Vivo.

Fluorosis can induce neurotoxicity. Sodium butyrate (SB), a histone deacetylase inhibitor, has important research potential in correcting glucose metabolism disorders and is widely used in a variety of neurological diseases and metabolic diseases, but it is not yet known whether it plays a role in combating fluoride-induced neurotoxicity. This study aims to evaluate the effect of SB on fluoride neurotoxicity and the possible associated mechanisms. The results of HE staining and Morris water maze showed that, in mice exposed to 100 mg/L fluoride for 3 months, the hippocampal cells arranged in loosely with large cell gaps and diminished in number. One thousand milligram per kilogram per day SB treatment improved fluoride-induced neuronal cell damage and spatial learning memory impairment. Western blot results showed that the abundance of malate dehydrogenase 2 (MDH2) and pyruvate dehydrogenase (PDH) in the hippocampus of fluorosis mice was increased, the abundance of pyruvate kinase M (PKM), lactate dehydrogenase (LDH), hexokinase (HK), phosphatidylinositol 3-kinase (PI3K), phosphorylated Akt (P-AKT), and hypoxia-inducible factor 1α (HIF-1α) was inhibited, and the content of lactate and ATP was decreased. SB treatment reversed the decreased glycolysis in the hippocampus of fluorosis mice. These results suggested that SB could ameliorate fluorosis-induced neurotoxicity, which might be linked with its function in regulating glycolysis as well as inhibition of the PI3K/AKT/HIF-1α pathway. Sodium butyrate ameliorates fluorosis-induced neurotoxicity by regulating hippocampal glycolysis in vivo (created with MedPeer (www.medpeer.cn)).

Genome-wide identification and characterization of NHL gene family in response to alkaline stress, ABA and MEJA treatments in wild soybean (Glycine soja).

Background: NDR1/HIN1-like (NHL) family genes are known to be involved in pathogen induced plant responses to biotic stress. Even though the NHL family genes have been identified and characterized in plant defense responses in some plants, the roles of these genes associated with the plant abiotic stress tolerance in wild soybean is not fully established yet, especially in response to alkaline stress. Methods: We identified the potential NHL family genes by using the Hidden Markov model and wild soybean genome. The maximum-likelihood phylogenetic tree and conserved motifs were generated by using the MEME online server and MEGA 7.0 software, respectively. Furthermore, the syntenic analysis was generated with Circos-0.69. Then we used the PlantCARE online software to predict and analyze the regulatory cis-acting elements in promoter regions. Hierarchical clustering trees was generated using TM4: MeV4.9 software. Additionally, the expression levels of NHL family genes under alkaline stress, ABA and MEJA treatment were identified by qRT-PCR. Results: In this study, we identified 59 potential NHL family genes in wild soybean. We identified that wild soybean NHL family genes could be mainly classified into five groups as well as exist with conserved motifs. Syntenic analysis of NHL family genes revealed genes location on 18 chromosomes and presence of 65 pairs of duplication genes. Moreover, NHL family genes consisted of a variety of putative hormone-related and abiotic stress responsive elements, where numbers of methyl jasmonate (MeJA) and abscisic acid (ABA) responsive elements were significantly larger than other elements. We confirmed the regulatory roles of NHL family genes in response to alkaline stress, ABA and MEJA treatment. In conclusion, we identified and provided valuable information on the wild soybean NHL family genes, and established a foundation to further explore the potential roles of NHL family genes in crosstalk with MeJA or ABA signal transduction mechanisms under alkaline stress.

Pb Transfer Preference of Arbuscular Mycorrhizal Fungus Rhizophagus irregularis in Morus alba under Different Light Intensities.

Arbuscular mycorrhizal (AM) fungi can improve the lead (Pb) tolerance of host plants and accumulate intensive Pb in mycorrhizal roots. However, the detailed contribution of AM fungal extraradical hyphae to the plants' Pb uptake remains unknown. In this study, mulberry (Morus alba) colonized by the AM fungus (Rhizophagus irregularis) with light treatments were linked by fungal extraradical hyphae using a three-compartment system (pot test), and their differences in responding to Pb application were compared. Shading inhibited mulberry photosynthesis and the growth of mulberry. In this study, Pb application did not affect the colonization of R. irregularis when symbiosis had already formed as the root was not exposed to Pb during the colonization and formation of the AM fungal hyphae network. The R. irregularis preferred to transfer more Pb to the unshaded mulberry than to the shaded mulberry, a condition capable of providing more C supply for fungal survival than to low-light mulberry. The Pb transferred through the mycorrhizal pathway to mulberry had low mobility and might be compartmented in the root by R. irregularis until exceeding a threshold. The relatively high expressions of MaABCG16 with high Pb concentrations in plants suggest that MaABCG16 might play an important role in Pb translocation.

Comparison of protective effects of alprostadil with Salvia miltiorrhiza against myocardial ischemia-reperfusion injury in rats.

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.