Hydromassage of macular hole edges for large and persistent full-thickness macular holes.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8.

Barrett's esophagus (BE) belongs to a pathological phenomenon occurring in the esophagus, this paper intended to unveil the underlying function of miR-378a-5p and its target TSPAN8 in BE progression. GEO analysis was conducted to determine differentially expressed genes in BE samples. Non-dysplastic metaplasia BE samples, high-grade dysplastic BE samples and controls were collected from subjects. CP-A and CP-B cells were exposed to bile acids (BA) to mimic gastroesophageal reflux in BE cells. RT-qPCR as well as western blot were applied for verifying expressions of miR-378a-5p, TSPAN8, CDX2 and SOX9. CCK-8, wound scratch together with Transwell assays were exploited for ascertaining cell proliferation, migration as well as invasion. The targeted relationship of miR-378a-5p and TSPAN8 could be verified by correlation analysis, dual-luciferase reporter experiment, and rescue experiments. Through analyzing GSE26886 dataset, we screened the most abundantly expressed gene TSPAN8 in BE samples. miR-378a-5p was reduced whereas TSPAN8 was elevated in CP-A as well as CP-B cells after triggering with BA. Knocking down TSPAN8 could counteract BA-triggered enhancement in BE cell proliferation, migration along with invasion. miR-378a-5p could suppress BE cell proliferation, and migration along with invasion via targeting TSPAN8. In BE, miR-378a-5p targeted TSPAN8 to inhibit BE cell proliferation, and migration along invasion. miR-378a-5p deletion or elevation of TSPAN8 may be key point in regulating CDX2 and SOX9 levels, thereby promoting BE formation.

Detection of Retinal Microvascular Changes with Optical Coherence Tomography Angiography in Patients with Acute Leukemia Without Retinopathy.

INTRODUCTION: Acute leukemia often affects microcirculation perfusion. This study aimed to investigate retinal microvascular changes in patients with acute leukemia without retinopathy during clinical remission using optical coherence tomography angiography (OCTA) and to determine the correlation of these changes with systemic laboratory values. METHODS: Thirty-eight patients in remission from acute leukemia with no retinopathy (NLR group) and 36 age-matched healthy individuals (control group) were included in this cross-sectional study. OCTA parameters, including the central foveal thickness (CFT), foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), foveal density (FD300), and the vessel densities (VDs) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris were analyzed in a 6 × 6 mm2 macular scan. Correlation and multiple linear regression analyses were conducted to identify potential systemic characteristics associated with these OCTA metrics. RESULTS: AI (P = 0.034) and FD300 (P < 0.001) differed significantly between the NLR and control groups. The VD of SCP in the parafovea (P = 0.001) and of DCP in both the parafovea (P = 0.011) and perifovea (P = 0.001) were significantly lower in the NLR group than in the control group. In a multiple linear regression analysis, the reduced VD of the perifoveal DCP was significantly correlated with the increased international normalized ratio (standardized beta [STD ß] = - 0.356; P = 0.047). CONCLUSIONS: Macular microvascular changes can be observed during remission from acute leukemia antecedent to clinically visible retinal lesions. Hematological disturbances may be associated with microvascular impairments in preclinical leukemic retinopathy.

Does COVID-19 affect mental health and substance use in young adults?

BACKGROUND: Mental health has been impacted by COVID-19 throughout the United States and beyond. The mental health and well-being were further affected with excessive substance use during the pandemic. The aim of this research was to explore how the COVID-19 affects the mental health of the young adults (18-24 years) in the South Jersey area. We also examined the association between mental health symptoms in young adults and substance use during the first and second year of the pandemic. METHODS AND MATERIAL: A cross-sectional survey was conducted with (n = 711) 527 participants that included young adults (18-24 years old) across university campus in south jersey and in the community cohorts. Multinomial regression analysis and Chi-squared test were used to explore the association between mental symptoms and substance use. Data were analyzed using Microsoft Excel Spreadsheet for descriptive statistics and Python 3.0 scikit-learn package. RESULTS: The study showed that "Lonely" and "Hopeless" were the top two mental health symptoms. It was observed that the symptoms of "Lonely" and "Hopeless" increased for both males and females. In general, males seemed to be affected more than females in this study for mental health symptoms. For substance use, "Nervous" and "Smoking" showed positive correlation in 2020 and "Hopeless" and "Alcohol" were positively correlated in 2021. CONCLUSIONS: Young adults' mental health symptoms and substance use has been proven to be affected through the pandemic and this research results even though localized will assist the community and educational institutions to plan better support to assist young adults with better health and wellness initiatives.

Unilateral isolated optic nerve infiltration combined with central retinal artery occlusion in a patient with acute myeloid leukemia.

Purpose: To report a case of unilateral isolated optic nerve infiltration combined with central retinal artery occlusion in a patient with acute myeloid leukemia. Observations: A 28-year-old acute myeloid leukemia patient with systemic remission after hematopoietic stem cell transplantation presented with optic nerve infiltration combined with central retinal artery occlusion. Fundus examination showed diffuse papillary swelling with blurred margins and whitening macular with cherry-red spot. CBFß-MYH11 fusion transcript analysis revealed central nervous system relapse of acute myeloid leukemia and optic nerve infiltration. Conclusions and importance: Isolated optic nerve infiltration combined with central retinal artery occlusion is an extremely rare presentation in acute myeloid leukemia. Even in the absence of cytological and radiographic evidence from cerebrospinal fluid, optic nerve infiltration should not be ignored.

Organophosphorus and Iron Catalysis: Good Partners for Hydrometalation of Olefins and Alkynes.

The last decades have seen an impressive development of iron complexes involving organophosphorus ligands applied in homogeneous catalyzed hydrometalation of olefins and alkynes. Two main topics will be covered in this JOCSynopsis: (i) an overview of the achievements in the area of iron-catalyzed hydrophosphination and then (ii) hydrosilylation, hydroborylation, and hydromagnesiation reactions promoted by catalysts based on organophosphorus ligands and iron.

Iron-Catalysed Reductive Amination of Carbonyl Derivatives with ω-Amino Fatty Acids to Access Cyclic Amines.

An efficient method for the reductive amination of carbonyl derivatives with ω-amino fatty acids catalysed by an iron complex Fe(CO)4 (IMes) [IMes=1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] by means of hydrosilylation was developed. A variety of pyrrolidines, piperidines and azepanes were selectively synthesised in moderate-to-excellent yields (36 examples, 47-97 % isolated yield) with a good functional group tolerance.

Iron Catalysis in Reduction and Hydrometalation Reactions.

The last two decades have seen an impressive improvement of the use of iron as a fascinating and valuable alternative transition metal in homogeneous catalysis in terms of sustainability and economy. It was efficiently used in catalytic organic synthetic transformations, which in particular include the reduction of unsaturated bonds. This review summarizes the fast development and the recent advances in selective reductions of olefins, alkynes, carbonyl and carboxylic derivatives, imines, and nitro compounds promoted by iron catalysts. The topical hydrogen-borrowing reactions and hydroboration of unsaturated compounds are also reported. It is hoped that this account not only provides an overview of the state of the art in iron catalysis but also stimulates the development of superior greener catalytic systems in the near future.

Synthesis, in vitro cytotoxicity, and structure-activity relationships (SAR) of multidentate oxidovanadium(iv) complexes as anticancer agents.

Multidentate oxidovanadium(iv) complexes with different geometric configurations [VO(ox)(bpy)(H2O)] 1, [VO(ox)(phen)(H2O)] 2, [VO(ida)(bpy)]·2H2O 3, (phen)[VO(ida)(phen)]·4H2O 4, and (Hphen)[VO(H2O)(nta)]·2H2O 5 [ox = oxalic acid, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, ida = iminodiacetic acid, nta = nitrilotriacetic acid] have been obtained from the reactions of oxidovanadium sulfate or vanadium pentoxide with oxalates, amino-polycarboxylates and N-heterocyclic ligands in neutral solution by the hydrothermal method, and have been fully characterized by elemental, thermogravimetric analyses and single crystal X-ray diffraction, as well as a wide range of spectroscopic techniques such as FT-IR, UV/Vis, NMR, ESI-MS. The anti-tumor properties of oxidovanadium compounds 1-5 were further evaluated in human HepG2 and SMMC-7721 hepatocellular carcinoma cell lines in vitro. The profiles of cytotoxicity, cell cycle distribution, as well as cell apoptosis upon test compound exposure, were determined by MTT and flow cytometry assays. Compound 2 exhibited a much higher anti-tumor activity than others. The IC50 values of 2 were 5.34 ± 0.034 µM and 29.07 ± 0.017 µM in SMMC-7721 and HepG2 cells after 48 h treatment, respectively. Furthermore, compound 2 could significantly arrest the cell cycle in the S and G2/M phases and further induce cell apoptosis in a dose-dependent manner. The structure-activity relationship (SAR) studies revealed that structural elements, for example, metal components, variations of coordination mode, labile water molecules, chelated ligands etc., probably exert an essential cooperative effect on the antitumor activity. In short, these findings not only provide an accessible model system to exploit V-based complexes as potential simple, safe and effective multifunctional antitumor agents, but also open up a rational approach to shed new light on the selection and optimization of ideal drug candidates.

Significantly lengthened telomere in granulosa cells from women with polycystic ovarian syndrome (PCOS).

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. However, its etiology remains poorly understood. Recent studies indicated that telomere length was related to PCOS. However, the association between telomere length and PCOS has only been shown in leucocytes and remained controversial across different studies. To clarify the association between telomere length and PCOS, the current study interrogated telomere length not only in leucocytes, but also in follicular granulosa cells, which is essential for folliculogenesis and steroidogenesis. METHODS: Seventy-five patients with PCOS and 81 controls with mechanical infertility undergoing their first in vitro fertilization cycle were enrolled. Their peripheral blood and granulosa cells were collected on the oocyte retrieval day. Telomere length of both leucocytes in the blood and granulosa cells was assayed by quantitative polymerase chain reaction. RESULTS: No significant difference was found in the leucocyte telomere length between controls and PCOS patients (0.99 ± 0.44 vs. 1.00 ± 0.38, p = 0.93). Interestingly, when comparing telomere length in granulosa cells between controls and PCOS subjects, significantly lengthened telomere length was found in PCOS subjects (1.00 ± 0.37 vs. 1.57±0.67, p < 0.0001). After adjustments for age and body mass index, the p value remained significant (p < 0.0001). CONCLUSIONS: This finding reinforced the association between telomere abnormalities and PCOS. Given the importance of telomere length in cellular proliferation, our findings provided novel insights into the pathophysiology of PCOS that abnormalities in telomere length possibly disturb folliculogenesis and subsequently result in PCOS.

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome.

BACKGROUND: DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS. METHODS: Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR. RESULTS: Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (-443, -431, -403, -371, -331, -120, -49, -5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose-dependent relation. CONCLUSION: Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

A novel functional variant in Wilms' Tumor 1 (WT1) is associated with idiopathic non-obstructive azoospermia.

Idiopathic nonobstructive azoospermia (INOA) is one of the most severe forms of male infertility, yet its pathophysiology remains unclear. WT1 (Wilms' tumor 1) regulates the polarity of Sertoli cells, thereby playing a critical, indirect role in spermatogenesis. Here, we evaluated WT1 gene variation associates with INOA by assessing its promoter and coding regions in 200 patients diagnosed with INOA and 200 proven-fertile men. Three novel variants in the WT1 coding region were detected only in INOA patients, including two synonymous variants and one missense variant, p.Phe435Leu (p.F435L), which was predicted to be deleterious to protein function. The results of dual luciferase reporter showed that the WT1 p.F435L variant decreases transcription of COL4A1 and WNT4 promoters through a dominant-negative effect. Furthermore, chromatin immunoprecipitation assays revealed that COL4A1 and WNT4 promoter is directly bound by wild-type WT1 protein, but not the p.F435L WT1 variant. Thus, we identified a novel functional variant of WT1 functionally associated with INOA. Mol. Reprod. Dev. 84: 222-228, 2017. © 2017 Wiley Periodicals, Inc.

Good quality blastocyst from non-/mono-pronuclear zygote may be used for transfer during IVF.

Although healthy infants have developed from non- and mono-pronuclear zygotes, the transfer of embryos from non- and mono-pronuclear zygotes is not recommended because there are no proper selection criteria. In the present study, we discuss how to select non- and mono-pronuclear embryos with the highest developmental potential at 19-20 hours post-insemination. We found that the percentage of blastocysts with normal chromosome constitution in non-pronuclear zygotes was slightly higher than in mono-pronuclear zygotes. Non- and mono-pronuclear embryos that were at the 4-cell stage on D2 and/or at the 6- to 8-cell stage on D3 had higher incidence rates of blastocysts with normal chromosome constitutions. We also found higher incidences of blastocysts with normal chromosome constitution on D6 than on D5. The results suggest that if high quality non- and mono-pronuclear zygotes develop to the 4-cell stage on D2 and the 6-to 8- cell stages on D3, along with high quality D6 blastocysts, the incidence of blastocysts with normal chromosome constitution is higher.

An anti-let-7 sponge decoys and decays endogenous let-7 functions.

The let-7 family contains 12 members, which share identical seed regions, suggesting that they may target the same mRNAs. It is essential to develop a means that can regulate the functions of all members. Using a DNA synthesis technique, we have generated an anti-let-7 sponge aiming to modulate the function of all members. We found that products of the anti-let-7 construct could bind and inactivate all members of the let-7 family, producing decoy and decay effects. To test the role of the anti-let-7 sponge, we stably expressed the anti-let-7 construct in two types of cells, the breast carcinoma cells MT-1 and the oldest and most commonly used human cervical cancer cell line, HeLa cells. We found that expression of anti-let-7 increased cell survival, invasion and adhesion, which corroborate with known functions of let-7 family members. We further identified a novel target site across all species of the let-7 family in hyaluronan synthase 2 (HAS2). HAS2 overexpression produced similar effects as the anti-let-7 sponge. Silencing HAS2 expression by siRNAs produced opposite effects to anti-let-7 on cell survival and invasion. The ability of anti-let-7 to regulate multiple members of the let-7 family allows us to observe their multiple functions using a single reagent. This approach can be applied to other family members with conserved sequences.

mTOR partly mediates insulin resistance by phosphorylation of insulin receptor substrate-1 on serine(307) residues after burn.

Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4 mg/kg, i.p.) was injected 2 h before euglycemic-hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine³°7, phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-α, insulin and C-peptide were determined before and after euglycemic-hyperinsulinemic glucose clamps. Our data showed that TNF-α, insulin and C-peptide significantly increased in the early stage after burn (P < 0.01). The infused rates of total 10% glucose (GIR, mg/kg min) significantly decreased at 4 days after burn. The level of IRS-1 serine³°7 phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine³°7 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-α, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn.

Binding characteristics between poly(ethylene glycol) and hydrophilic modified ibuprofen in aqueous solution.

The solubility of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), is enhanced by synthesizing ibuprofen ester with a water-soluble polymer, poly(ethylene glycol) (PEG), and the product obtained functions as a nonionic surfactant (IBF-PEG800, IP800). The morphology and aggregation behavior of IP800 micelles and IP800/PEG complexes in aqueous solution are investigated by (1)H NMR technology, dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and fluorescence resonance energy transfer (FRET). The microstructure of IP800 micelles is strongly related to the concentration of IP800. IP800 monomers can form looser micelles at relatively low concentrations and much tighter micelles at high concentrations. And the binding model of PEG with looser IP800 micelles dramatically depends on the molecular weight and concentration of PEG: PEG with lower molecular weight (MW < or = 2000 Da) inserts to the interface of the hydrophilic corona and hydrophobic core of IP800 micelles; PEG with higher molecular weight (MW > 2000 Da) binds to the surface of IP800 micelles, and one long PEG chain (6000 < MW < or = 20000 Da) wraps several IP800 micelles. Besides, the ratio of short chain PEG400 to IP800 micelles of the IP800/PEG complex is about 15:1 at a fixed concentration of IP800 (0.05 mM), and for the long chain PEG20000 it is 1:3-1:4.

Auditing complex concepts in overlapping subsets of SNOMED.

Limited resources and the sheer volume of concepts make auditing a large terminology, such as SNOMED CT, a daunting task. It is essential to devise techniques that can aid an auditor by automatically identifying concepts that deserve attention. A methodology for this purpose based on a previously introduced abstraction network (called the p-area taxonomy) for a SNOMED CT hierarchy is presented. The methodology algorithmically gathers concepts appearing in certain overlapping subsets, defined exclusively with respect to the p-area taxonomy, for review. The results of applying the methodology to SNOMED's Specimen hierarchy are presented. These results are compared against a control sample composed of concepts residing in subsets without the overlaps. With the use of the double bootstrap, the concept group produced by our methodology is shown to yield a statistically significant higher proportion of error discoveries.

Activation of p38 MAPK by reactive oxygen species is essential in a rat model of stress-induced gastric mucosal injury.

Stress ulceration is a common complication in critically ill patients and can result in significant upper gastrointestinal bleeding associated with a high morbidity and mortality. At present, little is known of the molecular mechanisms underlying the incidence of this type of gastric damage. In the present study, we investigated the temporal activation of the redox-sensitive p38 signaling transduction cascade and its roles in a well-defined experimental model of cold immobilization stress-induced gastric ulceration. Exposure of Sprague-Dawley rats to 6 h of cold immobilization stress led to a rapid activation of p38 in the gastric mucosa at as early as 15 min after stress, and this activation was maximal after 1.5 h of stress and still persisted until the end of stress. Selectively blocking p38 by pretreatment with SB 239063, a potent and selective p38 inhibitor, suppressed the stress-promoted TNF-alpha, IL-1beta, and CINC-1 production and then prevented the subsequent neutrophil infiltration, gastric mucosal epithelial necrosis and apoptosis, and the ulcerative lesions formation. Prior administration of the free radical scavengers, tempol and N-acetyl-L-cysteine, abolished the stress induction of p38 activation and the resulting mucosal inflammation and gastric injury. These results demonstrate that reactive oxygen species-mediated p38 activation plays an essential role in the pathogenesis of stress-induced gastric inflammatory damage in the rat model of cold immobilization stress. Our findings suggested that inhibition of p38 activation might be a potential strategy for the prophylaxis and treatment of stress ulceration.

[Role of c-Jun NH (2)-terminal kinase in insulin resistance after burn].

OBJECTIVE: To investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups. RESULTS: The infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn. CONCLUSIONS: The activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.

[Interaction between p38 mitogen-activated protein kinase signal transduction pathway and NF-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma].

OBJECTIVE: To investigate the interaction between p38 mitogen-activated protein kinase signal transduction pathway and nuclear factor (NF)-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma. METHODS: Human monocyte line THP-1 were incubated with serum from eight healthy controls, burn sera, burn sera pretreatment with SB203580, and burn sera pretreatment with pyrrolidine dithiocarbamate (PDTC). After 24 hours incubation with serum, tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels in THP-1 culture supernatants were measured by ELISA. The activities of p38 MAPK and expressions of IkappaBalpha in THP-1 were measured by Western blot analysis. The EMSA method was used to characterize the binding activities of NF-kappaB and activating protein (AP)-1 in THP-1. RESULTS: In comparison with normal controls, burn sera resulted in a significant higher level release of TNF-alpha and IL-1beta in THP-1 [(7.30 +/- 0.84) ng/ml vs (2.20 +/- 0.28) ng/ml, P < 0.05; (2.88 +/- 0.38) ng/ml vs (0.81 +/- 0.14) ng/ml, P < 0.05], which were significantly inhibited by pretreatment with SB203580 or PDTC. Burn sera showed increased activities of p38 MAPK and AP-1 in THP-1 (4728 +/- 582 vs 1291 +/- 163, P < 0.05; 946 +/- 137 vs 361 +/- 40, P < 0.05), which were abolished by pretreatment with SB203580 but not PDTC. The expression of IkappaBalpha in THP-1 incubated with burn sera was significantly decreased than those incubated with control sera (1211 +/- 115 vs 2658 +/- 318, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580. Burn sera also leaded to an increased activity of NF-kappaB in THP-1 (1636 +/- 170 vs 317 +/- 32, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580. CONCLUSIONS: There are no direct interaction between p38 MAPK signal transduction pathway and NF-kappaB/IkappaB pathway. These two pathways, which regulate the production of TNF-alpha and IL-1beta in monocyte following burn trauma, are parallel and independent.