MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Potential correlation of oral flora with pemphigus vulgaris - A case control study.

Background/purpose: Oral flora is related to various immune-related diseases. Herein we explored the characteristics of oral flora in patients with pemphigus vulgaris (PV) and analyzed the correlation between oral flora and PV. Materials and methods: Twenty-two untreated patients with PV and 12 healthy controls (HC) were included in this case-control study. The characteristics of salivary microbiome were assessed by high-throughput sequencing using the 16S rRNA Illumina MiSeq approach, and differences between the PV and HC groups were determined. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was applied to screen key metabolic pathways and preliminarily explore potential mechanisms underlying PV occurrence and development. Results: The abundance of oral flora in the PV group was significantly lower than that in the HC group, and there were characteristic changes. The relative abundance of Prevotella and Agrobacterium in the PV group was significantly higher than that in the HC group (P < 0.05) and that of Neisseria, Lautropia, and Fusobacterium was significantly lower (P < 0.05). There was a linear correlation between Prevotella and serum Dsg3 level in PV. KEGG pathway analyses indicated significant differences in nine metabolic pathways between the PV and HC groups (P < 0.05), namely carbohydrate metabolism, digestive system, neurodegenerative disease, glycan biosynthesis and metabolism, drug resistance: antimicrobial, infectious disease: viral, circulatory system, excretory system, and nervous system. Conclusion: The oral flora of patients with PV presented characteristic changes, and several metabolic pathways were affected, including N-glycan biosynthesis and metabolism. Prevotella spp. appear to require the most attention in PV. We believe that oral flora dysbacteriosis contributes to PV occurrence and development.

Brucellosis complicated by myelofibrosis: report of five cases and review of literature.

Myelofibrosis is a myeloproliferative tumor, that can be secondary to malignant hematologic or inflammatory diseases, such as chronic myeloid leukemia, polycythemia vera, primary thrombocythemia, multiple myeloma, disseminated tuberculosis, or vasculitis. However, few cases of brucellosis-associated myelofibrosis have been reported. Moreover, due to the rarity of this phenomenon, it is often overlooked by clinicians, resulting in misdiagnosis and mismanagement. Thus, brucellosis should be considered as a possible cause of myelofibrosis. In the present study, we report five cases of brucellosis, of which three had myelofibrosis. In addition, to further determine the potential link between brucellosis and myelofibrosis, we retrospectively analyzed the levels of various cytokines by collecting the clinicopathologic data of patients and using immunohistochemical staining. We found that brucellosis patients with myelofibrosis had elevated levels of cytokines such as interferon (IFN)-γ, interleukin (IL)-1ß, basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), suggesting that the regulation of cytokines may play a central role in the development of myelofibrosis in patients with brucellosis.

[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) causes high morbidity and mortality in infants, but no effective preventive or therapeutic agents have been developed to combat BPD. In this study, we assessed the expression of MALAT1 and ALOX5 in peripheral blood mononuclear cells from BPD neonates, hyperoxia-induced rat models and lung epithelial cell lines. Interestingly, we found upregulated expression of MALAT1 and ALOX5 in the experimental groups, along with upregulated expression of proinflammatory cytokines. According to bioinformatics prediction, MALAT1 and ALOX5 simultaneously bind to miR-188-3p, which was downregulated in the experimental groups above. Silencing MALAT1 or ALOX5 and overexpressing miR-188-3p inhibited apoptosis and promoted the proliferation of hyperoxia-treated A549 cells. Suppressing MALAT1 or overexpressing miR-188-3p increased the expression levels of miR-188-3p but decreased the expression levels of ALOX5. Moreover, RNA immunoprecipitation (RIP) and luciferase assays showed that MALAT1 directly targeted miR-188-3p to regulate ALOX5 expression in BPD neonates. Collectively, our study demonstrates that MALAT1 regulates ALOX5 expression by binding to miR-188-3p, providing novel insights into potential therapeutics for BPD treatment.

Sequential 2.5 mg letrozole/FSH therapy is more effective for promoting pregnancy in infertile women with PCOS: a pragmatic randomized controlled trial.

Study question: In infertile women with polycystic ovary syndrome (PCOS), is the sequential use of letrozole 2.5 mg/follicle stimulating hormone(FSH) more effective than letrozole 5 mg/FSH in stimulating ovulation and promoting pregnancy? Research design and methods: The study was designed as a prospective, single-center, randomized, controlled pragmatic clinical trial. 220 infertile women between the ages of 20 and 40, who matched the Rotterdam criteria for PCOS and had no other identified reasons for infertility were enrolled from April 2023 to July 2023.The participants were randomly assigned to two groups in a 1:1 ratio. One group received 2.5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110), while the other group received 5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110). The duration of FSH treatment varied depending on the follicular development stage. Each participant underwent one to three treatment cycles until achieving pregnancy.The primary outcome was the cumulative pregnancy rate of all the participants. Secondary outcomes included characteristics and clinical pregnancy rates of all the intervention cycles. Results: For all 220 participants, the sequential letrozole 2.5 mg/FSH treatment group had a significantly higher cumulative pregnancy rate compared to the letrozole 5 mg/FSH treatment group (72.7% versus 59.1%, RR (95%CI) = 1.23 (1.02, 1.49), P-value = 0.033). For all 468 intervention cycles, letrozole 2.5 mg/FSH group had a significantly higher clinical pregnancy rate than the letrozole 5 mg/FSH group (36.2% versus 26.3%, P-value = 0.021), no statistically significant differences were observed in ovulation rates or adverse effects. Conclusions: The data indicate that the sequential letrozole 2.5mg/FSH protocol may be more effective than the sequential letrozole 5mg/FSH protocol for promoting pregnancy in infertile women with PCOS. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2300069638.

[Isoquinoline alkaloids from two species of Thalictrum genus plants].

The chemical constituents from the roots of Thalictrum cultratum and T. baicalense were investigated. By various isolation methods, such as silica gel, aluminium oxide, ODS, and Sephadex LH-20 column chromatographies, and semi-preparative HPLC, 11 simple isoquinoline alkaloids were isolated from the ethanol extract of the roots of these two plants, including a new compound, named dehydrothalflavine(1), and ten known ones(2-11): N-methylcorydaline(2), N-methylthalidaldine(3), thaliflavine(4), oxyhydrastinine(5), noroxyhydrastinine(6), dimethoxyisoquinolone(7), thalactamine(8), dehydronoroxyhydrastinine(9), 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline(10), and isopicnarrhine(11). Their structures were elucidated on the basis of HR-ESI-MS and 1 D and 2 D NMR techniques. Compound 1 was a new isoquinoline alkaloid. Compound 11 was obtained from Tha-lictrum plant for the first time. All compounds did not show cytotoxic activities against HL-60, U937, HCT116, Caco-2, and HepG2 cancer cell lines.

Skimmianine as a novel therapeutic agent suppresses proliferation and migration of human esophageal squamous cell carcinoma via blocking the activation of ERK1/2.

Esophageal squamous cell carcinoma (ESCC), one of the main histopathological subtypes of esophageal cancer (EC), is characterized by high morbidity and mortality. Clinical treatment for ESCC lacks specific molecular targets and effective therapeutic drugs. Skimmianine (SK), one of the natural fluroquinolone alkaloids, is widely present in Rutaceae family plants. Here, we mainly used CCK-8 assay, clone formation, flow cytometry analysis, wound-healing assay, Transwell assay, western blot, quantitative real-time PCR (qRT-PCR), molecular docking analysis, tumor xenograft assay, and immunohistochemistry (IHC) staining to investigate the potential anti-tumor effect of SK on ESCC. We demonstrated that SK inhibited the proliferation of TE-1 and Eca109 cells via inducing the G0/G1 phase cell cycle arrest, prevented the migration and invasion of tumor cells via regulating epithelial-mesenchymal transition (EMT) in vitro. In addition, SK obviously suppressed the growth of xenografted Eca109 tumors in nude mice. The anti-tumor mechanism of SK could be blocking the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Our basic research suggests that SK can be a potential therapeutic agent for ESCC.

[Pollution Characteristics and Health Risk Assessment of Perfluorinated Compounds in PM2.5 in Zhejiang Province].

As typical new pollutants, perfluorinated compounds (PFCs) have been widely concerned by environmental workers in recent years. This study was carried out to investigate the pollution characteristics of perfluorinated compounds in atmospheric particulate matter (PM2.5) in Zhejiang Province. The chemical extraction of PM2.5 was performed using the accelerated solvent extraction (ASE) method with mixed dichloromethane and acetone (2:1). The chemical analysis was implemented by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that the daily average concentration of the sum of 12 PFCs (Σ12 PFCs) ranged from 131.63 pg·m-3 to 578.53 pg·m-3, which was slightly higher in winter compared to that in autumn. The concentrations of perfluorosulfonic acids (PFSAs) were much lower than those of perfluorocarboxylic acids (PFCAs). PFOS was the primary contaminant among PFASs, with an average concentration of 12.90 pg·m-3. The content of PFCAs exhibited a trend of PFOA>PFHxA>PFHpA, and the detection rate of long-chain PFCs was much lower than that of short-chain PFCs. The hysplit-4 model was used to calculate the QZ air mass transport trajectory. The results indicated that the backward trajectory of this point was significantly different along time, and the source of air mass rarely affected the concentration. The forward trajectory confirmed that PFCs can be transmitted over long distances in the atmosphere in a short time. The correlation coefficient between PFUdA and PFTeDA was evaluated to be 0.68, and that between PFHxS and PFOS was 0.66, suggesting the same sources of these chemicals. The content of PFCs was positively correlated with PM2.5, indicating that people might suffer from higher health risks on haze days. The risk quotient estimation implied no health risk of PFCs in PM2.5 in Zhejiang Province.

Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

Effect and Safety of Tongyan Spray () on Hyoid Motion in Patients with Dysphagia after Ischemic Stroke.

OBJECTIVE: To observe the effects and safety of Tongyan Spray () on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia. METHODS: Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment. RESULTS: Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P<0.05). There were no obvious adverse reactions observed in oral mucosa in both groups during the whole study. CONCLUSION: Tongyan Spray was an effective and safe medicine for improving swallowing function in patients with ischemic post-stroke dysphagia.

Promotion of Bronchopulmonary Dysplasia Progression Using Circular RNA circabcc4 via Facilitating PLA2G6 Expression by Sequestering miR-663a.

Circular RNA (circRNA) has been increasingly proven as a new type of promising therapeutic RNA molecule in a variety of human diseases. However, the role of circRNA in bronchopulmonary dysplasia (BPD) has not yet been elucidated. Here, a new circRNA circABCC4 was identified from the Agilent circRNA chip as a differentially expressed circRNA in BPD. The relationship between circABCC4 level and BPD clinicopathological characteristics was analyzed. The function of circABCC4 was evaluated by performing CCK-8 and apoptosis analysis in vitro and BPD model analysis in vivo. RNA immunoprecipitation (RIP), luciferase reporter and rescue experiments were used to elucidate the interaction between circABCC4 and miR-663a. Luciferase reporter assay and rescue experiments were used to elucidate the interaction between PLA2G6 and miR-663a. CircABCC4 and PLA2G6 levels were increased, while miR-663a levels were decreased in the BPD group, compared to the control group. MiR-663a inhibited apoptosis by repressing PLA2G6 expression, while circABCC4 enhanced the apoptosis and inhibited the proliferation of A549 cells by sponging miR-663a and increasing PLA2G6 expression. In conclusion, circABCC4 promotes the evolving of BPD by spongening miR-663a and up-regulating PLA2G6 expression, which makes circABCC4 an ideal molecular target for early diagnosis and intervention of BPD.

Lipoxin A4 attenuates hyperoxia­induced lung epithelial cell injury via the upregulation of heme oxygenase­1 and inhibition of proinflammatory cytokines.

The present study examined whether lipoxin A4 (LXA4) increases the expression of HO­1, and inhibits the production of interleukin 6 (IL­6) and monocyte chemotactic protein 1 (MCP­1) in LXA4­induced protection during hyperoxia­induced injury in murine lung epithelial cells (MLE­12) and what signal pathway may participate in the actions of LXA4 inhibiting IL­6 and MCP­1. MLE­12 cells were exposed to air or hyperoxia with or without pretreatment with LXA4, Zinc protoporphyrin IX (ZnPP­IX), IL­6, anti­IL­6, MCP­1, anti­MCP­1, inhibitors of p38 mitogen­activated protein kinase (p38 MAPK), protein kinase B (Akt) and extracellular signal­regulated kinase 1/2 (ERK1/2) signaling pathways. The cell survival rates, cell viability, apoptosis rates, expression of superoxide dismutase (SOD), heme oxygenase­1 (HO­1), IL­6 and MCP­1, and the activations of p38 MAPK, ERK1/2 and Akt were measured. LXA4 significantly increased the cell survival rates, cell viability, SOD levels and HO­1 expression, reduced the apoptosis rates, and inhibited the MCP­1 and IL­6 levels induced by hyperoxia in cells. ZnPP­IX, an inhibitor of HO­1, blocked LXA4­induced protection on cell viability in cells exposed to hyperoxia. Anti­IL­6 and anti­MCP­1 improved the cell viability of cells exposed to hyperoxia. Inhibition of p38 MAPK and ERK1/2 blocked the expression of MCP­1 and IL­6 induced by hyperoxia. LXA4 inhibited the activation of p38 MAPK and ERK1/2 induced by hyperoxia, and increased the activation of the Akt signaling pathway, which was inhibited by hyperoxia. Therefore, LXA4 attenuated hyperoxia­induced injury in MLE­12 cells via the upregulation of HO­1 expression. The protection of LXA4 in hyperoxia­induced cell injury may be associated with the downregulation IL­6 and MCP­1 levels via the inhibition of the p38 MAPK and ERK1/2 signaling pathways.

Atomically Precise Gold-Levonorgestrel Nanocluster as a Radiosensitizer for Enhanced Cancer Therapy.

Gold nanoclusters have become promising radiosensitizers due to their ultrasmall size and robust ability to adsorb, scatter, and re-emit radiation. However, most of the previously reported gold nanocluster radiosensitizers do not have a precise atomic structure, causing difficulties in understanding the structure-activity relationship. In this study, a structurally defined gold-levonorgestrel nanocluster consisting of Au8(C21H27O2)8 (Au8NC) with bright luminescence (58.7% quantum yield) and satisfactory biocompatibility was demonstrated as a nanoradiosensitizer. When the Au8NCs were irradiated with X-rays, they produced reactive oxygen species (ROS), resulting in irreversible cell apoptosis. As indicated by in vivo tumor formation experiments, tumorigenicity was significantly suppressed after one radiotherapy treatment with the Au8NCs. In addition, compared with tumors treated with X-rays (4 Gy) alone, tumors treated with the nanosensitizer exhibited an inhibition rate of 74.2%. This study contributes to the development of atomically precise gold nanoclusters as efficient radiosensitizers.

Combination of Preoperative D-Dimer and Platelet Distribution width Predicts Postoperative Deep Venous Thrombosis in Patients with Cervical Carcinoma

Background: Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Platelet distribution width (PDW), a platelet index, indicates variation in platelet size. We aimed to investigate whether the combination of D-dimer and PDW could have a better performance in predicting DVT in patients with cervical carcinoma. Materials and Methods: In 198 consecutive cervical carcinoma patients without preoperative DVT, preoperative D-dimer and PDW levels were measured. Compression ultrasonography was performed in all cervical carcinoma patients before surgery, as well as one month, three months, six months, and 12 months. Results: During a median period of 12 months, 17 of the 198 patients (8.6 %) developed DVT. PDW levels were reduced and D-dimer levels were increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealed that both PDW and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.628 (95% CI: 0.556 to 0.695, p=0.142) when D-dimer was used alone, whereas it increased to 0.777 (95% CI: 0.712 to 0.833, p<0.011) with the addition of PDW. Incorporation of PDW into the D-dimer model significantly improved the predictive value. Conclusions: The combination of preoperative D-dimer and PDW improves the predictive power of postoperative DVT risk in patients with cervical carcinoma.

Motor imagery training induces changes in brain neural networks in stroke patients.

Motor imagery is the mental representation of an action without overt movement or muscle activation. However, the effects of motor imagery on stroke-induced hand dysfunction and brain neural networks are still unknown. We conducted a randomized controlled trial in the China Rehabilitation Research Center. Twenty stroke patients, including 13 males and 7 females, 32-51 years old, were recruited and randomly assigned to the traditional rehabilitation treatment group (PP group, n = 10) or the motor imagery training combined with traditional rehabilitation treatment group (MP group, n = 10). All patients received rehabilitation training once a day, 45 minutes per session, five times per week, for 4 consecutive weeks. In the MP group, motor imagery training was performed for 45 minutes after traditional rehabilitation training, daily. Action Research Arm Test and the Fugl-Meyer Assessment of the upper extremity were used to evaluate hand functions before and after treatment. Transcranial magnetic stimulation was used to analyze motor evoked potentials in the affected extremity. Diffusion tensor imaging was used to assess changes in brain neural networks. Compared with the PP group, the MP group showed better recovery of hand function, higher amplitude of the motor evoked potential in the abductor pollicis brevis, greater fractional anisotropy of the right dorsal pathway, and an increase in the fractional anisotropy of the bilateral dorsal pathway. Our findings indicate that 4 weeks of motor imagery training combined with traditional rehabilitation treatment improves hand function in stroke patients by enhancing the dorsal pathway. This trial has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-OCH-12002238).

Lipoxin A4 Attenuates Bronchopulmonary Dysplasia via Upregulation of Let-7c and Downregulation of TGF-ß1 Signaling Pathway.

Transforming growth factor-ß (TGF-ß) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF-ß antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF-ß antibodies, and let-7c mimic/anti-microRNA transfections. Treatment with 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies both attenuated the mice alveolar simplification induced by hyperoxia. Hyperoxia treatment significantly altered pulmonary basal mRNA and protein expressions of several important extracellular matrix (ECM) and ECM remodeling proteins including fibronectin, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), elastin, tenascin C, collagen I, and matrix metalloproteinase-1 (MMP-1). 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies suppressed the mRNA and protein expressions of TGF-ß1 and TGF-ßR1 but not TGF-ßR2 in the lungs exposed to hyperoxia. Treatment with LXA4 and anti-TGF-ß antibodies alleviated hyperoxia-induced injury of the NIH/3T3 cells identified by morphologic observation and flow cytometry, and expressions of ECM, ECM remodeling proteins, and TGF-ß1 signaling pathway, but reversed by transfection with let-7c anti-miRNA. LXA4 upregulated the let-7c expression in MLE-12 cells, transfection with let-7c anti-miRNA, inhibited the LXA4-induced let-7c expression in MLE-12 cells exposed to hyperoxia and reduced the relative luciferase activity of let-7c binding with let-7c binding sites of the TGF-ßR1 3' UTR. Treatment with 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies significantly improved histology, ECM, and ECM remodeling proteins in the lungs isolated from the murine BPD model induced by hyperoxia. The LXA4-imparted protective effects on hyperoxia-induced lung injury are mediated by upregulation of let-7c and inhibition of TGF-ß1 and subsequent downregulation of TGF-ß1 signaling pathway.

Interferon-α-induced CD100 on naïve CD8+ T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction.

Objectives We investigated the effects of CD100 on naïve CD8+ T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8+ T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8+ T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays. Results HCV infection reduced CD100 expression on CD8+ T cells, whereas IFN-α treatment significantly increased CD100 expression on naïve CD8+ T cells. The increased CD100 interacted with the CD72 receptor and enhanced PBMC cytokine secretion (IFN-γ and tumour necrosis factor-α) and cytotoxicity. Conclusions IFN-α-induced CD100 on naïve CD8+ T cells promotes PBMC cytokine secretion and cytotoxicity through CD100-CD72 signalling during HCV infection.

[Investigating mechanism of toxicity reduction by combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata on terms of proteins self-assembly].

The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.