Case of Congenital Hemolytic Anemia with ATP11C and ANK1 Variants.

A male infant of Han descent, with a G1P1 mother and gestational age of 40+4 weeks, was born via cesarean section owing to his mother having pregnancy complications, including premature rupture of membranes, chorioamnionitis, and gestational diabetes. On the first day after birth, routine blood examination showed that his total red blood cells count was 2.32 × 1012/L, hemoglobin count was 77 g/L, and C-reactive protein count was 48.99 mg/L. After receiving an anti-infection treatment for 10 days and two blood transfusions (100 mL in total), he was discharged from a neonatal intensive care unit (NICU). Accessory examinations showed that reticulocytes in the peripheral blood were significantly increased, the morphology of red blood cells was normal, and all hemolysis-related examinations were normal; bone marrow examinations showed that the proliferation of the red blood cell system was low and serum ferritin and vitamin B12 levels were elevated. Because of the unexplained hemolysis, a whole-exome sequencing examination was performed. The results showed a hemizygous variant of the ATP11C gene (c.3136a>t/p ile 1046phe) and a frame-shift variant of the ANK1 gene (c.937del/pala313 leufs*19). After a six-month follow-up, the serum ferritin and vitamin B12 levels had gradually decreased to normal levels, and hemoglobin and reticulocyte values were 97 g/L and 7.17%, respectively, in the peripheral blood. No splenomegaly was found in physical examination.

Gut microbiota alterations in children and their relationship with primary immune thrombocytopenia.

Introduction: Gut microbiota reportedly play a critical role in some autoimmune diseases by maintaining immune homeostasis. Only a few studies have examined the correlation between gut microbiota and the onset of primary immune thrombocytopenia (ITP), especially in children. The purpose of this study was to investigate changes in the composition and diversity of the fecal microbiota of children with ITP, as well as the correlation between such microbiota and the onset of ITP. Methods: Twenty-five children newly diagnosed with ITP and 16 healthy volunteers (controls) were selected for the study. Fresh stool samples were collected to identify changes in the composition and diversity of gut microbiota as well as for potential correlation analysis. Results: In ITP patients, the phyla that were most frequently encountered were Firmicutes (54.3%), followed by Actinobacteria (19.79%), Bacteriodetes (16.06%), and Proteobacteria (8.75%). The phyla that were predominantly found in the controls were, Firmicutes (45.84%), Actinobacteria (40.15%), Bacteriodetes (3.42%), and Proteobacteria (10.23%). Compared with those of the controls, the proportions of Firmicutes and Bacteriodetes in the gut microbiota of ITP patients were increased while the proportions of Actinobacteria and Proteobacteria were decreased. Furthermore, gut microbiota in ITP patients varied by age group, showed specific changes in diversity, and were correlated with antiplatelet antibodies. IgG levels were significantly positively correlated with Bacteroides (P<0.01). Conclusions: The gut microbiota of children with ITP are imbalanced, as shown by the increase in Bacteroidetes, which was positively correlated with IgG. Thus gut microbiota may contribute to ITP pathogenesis via IgG. Clinical Trial Registration: The clinical trial were registered and approved by the Institutional Review Committee of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University. Ethics number KY-2023-106-01.

Purification and structural analysis of a novel polysaccharide from Rehmannia Radix Praeparata.

In this paper, the purification, structure, and antioxidant activity of Rehmannia Radix Praeparata polysaccharide (RRPP) were studied. The RRPP was separated using DEAE-52 cellulose and Sephadex G-100. The RRPP consisted of xylose, glucose, rhamnose, galactose, and mannose in ratios of 10.64:5.58:3.52:1.39:1.0. No protein was detected in the RRPP fraction, and the molecular weight of RRPP was about 1.75 × 106 Da. The basic skeleton information was obtained using periodic acid oxidation-Smith degradation, and RRPP contained 1→, 1 → 2, 1 → 3, 1 → 4, 1 → 2,6, 1 → 4,6 or 1 → 6, 1 → 2,3, 1 → 2,3,4, and other glycosidic bonds. Fourier transform infrared spectroscopy also showed that RRPP has both α- and ß-glycosidic bonds. The in vitro antioxidant activity test showed that RRPP could potentialize scavenging effect on ABTS+· and its scavenging rate was 91.3%.

Predicting the efficacy of glucocorticoids in pediatric primary immune thrombocytopenia using plasma proteomics.

Objective: Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics. Methods: A four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method. Results: 47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers. Conclusion: This study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.

Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS/ERK/JNK pathway.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a frequent complication of diabetes mellitus (DM), with limited therapy at present. This study aimed to explore the role and mechanism of Ganoderma lucidum polysaccharide (GLP) on DMED. Methods: DMED was induced in the experimental rats [male 12-week-old Sprague-Dawley (SD) rats] by treatment with streptozotocin (60 mg/kg) and apomorphine (APO). Next, rats in the GLP low dose (GLP-L)/GLP high dose (GLP-H) groups were treated with GLP (100 or 400 mg/kg/d, respectively) for 8 weeks. Subsequently, erectile function was assessed by APO and electrostimulation of the cavernous nerve (CN). Serum or penile testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cyclic guanosine monophosphate (cGMP) contents were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress indicators in the corpus cavernosum (CC) were measured by corresponding kits, and histological changes in the CC were observed by hematoxylin-eosin (HE) and Masson staining. Additionally, the apoptosis index, caspase-3, caspase-9, and eNOS expression, and mitochondrial membrane potential (MMP) were also detected. Furthermore, quantitative polymerase chain reaction (qPCR) and western blot assays were conducted to determine the NOS, TGF-ß1 mRNA expression, ERK1/2, eNOS, JNK phosphorylation, and arginase II protein expression. Results: The erectile function test revealed that erectile dysfunction (ED) was alleviated in the DMED rats following treatment with GLP. Moreover, GLP upregulated the T and cGMP content, improved the oxidative stress and histological injuries of CC, and also inhibited the apoptosis and MMP loss of penile tissues in DMED rats. Furthermore, GLP treatment enhanced the mRNA expression of NOS and TGF-ß1 and suppressed the phosphorylation of ERK1/2, eNOS, and JNK, as well as the protein expression of arginase II in DMED rats. Conclusions: GLP ameliorated DMED by repairing the CC pathological damage and upregulating NOS expression and ERK/JNK phosphorylation, indicating that GLP may be a candidate drug for DMED therapy.

The prognostic effect on childhood acute lymphoblastic leukemia of CD34+CD38- expressed in leukemia cells.

OBJECTIVE: Acute lymphoblastic leukemia is the most common malignant disease in children. CD34 and CD38 are expressed in both normal and leukemia cells, but studies of their prognostic associations in childhood acute lymphoblastic leukemia are limited. The aim of this study was to investigate the prognostic effect of CD34 + CD38- leukemia cells in this childhood cancer. METHODS: From January 2014 to January 2019, children with newly diagnosed acute lymphoblastic leukemia were included in this study and followed up until July 2020. The participants were divided into CD34+ and CD34- groups according to CD34 expression level at diagnosis, and the CD34+ group was further divided into CD34 + CD38- and CD34 + CD38+ subgroups based on CD38 expression level. We tracked clinical biological features, therapeutic outcomes, and other patient data for comparisons. RESULTS: The OS and EFS did not differ significantly between the CD34+ and CD34- groups (both P > 0.05). CD34+CD38- group and CD34+CD38+ group were further compared. OS differed significantly between these two groups (χ2 = 3.89, P = 0.048), as did the recurrence rate (χ2 = 5.04, P = 0.025), but EFS did not (χ2 = 1.45, P > 0.05). Survival analysis in patients with recurrence showed a significantly higher OS for the CD34 + CD38+ group compared with the CD34 + CD38- group (χ2 = 5.08, P = 0.024). The CD34+CD38- group and CD34+CD38+ group were matched for propensity scores. When recurrence was compared in the two groups after matching, the difference was statistically significant (P < 0.001). CONCLUSION: CD34+ and CD34- expression does not differ by prognosis in children with acute lymphoblastic leukemia, but CD34 + CD38- may indicate a poor prognosis.

Fractional Exhaled Nitric Oxide (FeNO) Integrating Airway Hyperresponsiveness (AHR) Examination Promotes Etiologic Diagnosis and Treatment for Children with Chronic Cough.

BACKGROUND Chronic cough is the main reason why parents seek medical treatment for their children. This study aimed to evaluate changes in airway function and inflammation levels and associated values in diagnosing and treating chronic cough. MATERIAL AND METHODS This study involved 118 children with chronic cough, including 45 cough-variant asthma (CVA) patients, 53 upper-airway cough syndrome (UACS) patients, and 20 post-infection cough (PIC) patients. Chronic cough was diagnosed as described by guidelines of the American College of Chest Physicians for evaluating chronic cough. Pulmonary ventilation function and airway hyperresponsiveness (AHR) were evaluated. Fractional exhaled nitric oxide (FeNO) levels and eosinophilic airway inflammation were measured. Eosinophil (EOS) count in sputum was also examined. CVA patients were treated with inhaled glucocorticoids, which have anti-inflammatory effects. RESULTS FeNO and sputum EOS levels were higher in CVA patients compared with UACS and PIC patients (P<0.05). CVA patients demonstrated significantly higher small airway indexes, including 25% forced expiratory flow (FEF), 50% FEF, and 75% FEF, compared with UACS and PIC patients (P<0.05). FeNO level was positively correlated with EOS in sputum (r=0.468, P=0.0001) and cough symptom scores (r=0.402, P<0.05). FeNO, EOS, and cough symptoms were significantly improved in CVA patients after glucocorticoid treatment. AHR was improved in all chronic cough patients after treatment. Cough-relief CVA patients demonstrated significantly higher FeNO levels compared with those without cough relief (P<0.05). CONCLUSIONS FeNO integrating pulmonary function and AHR examination can improve etiologic diagnosis and treatment for chronic cough in children.

SPAG6 promotes cell proliferation and inhibits apoptosis through the PTEN/PI3K/AKT pathway in Burkitt lymphoma.

The main purpose of the present study was to elucidate the role of sperm­associated antigen 6 (SPAG6) in the occurrence and development of Burkitt lymphoma (BL) and explore the underlying molecular mechanisms. A correlation was observed between the expression of SPAG6 and the prognosis of patients with lymphoma using The Cancer Genome Atlas (TCGA) database analysis. It was demonstrated that the levels of SPAG6 in BL cells were higher compared with that in IM­9 cells by reverse transcription­PCR and western blot assays. Moreover, silencing of SPAG6 significantly decreased proliferation and increased apoptosis of Daudi and Raji cells, whereas SPAG6 overexpression exerted the opposite effects on CA46 and NAMALWA cells. When investigating the possible mechanism, it was first observed that the level of phosphatase and tensin homolog (PTEN) protein was significantly increased, while that of phosphorylated (p­)AKT protein was markedly reduced in the SPAG6­knockdown group compared with the blank control group in Daudi and Raji cells by western blot analysis. It was further ascertained whether the phosphoinositide 3­kinase (PI3K)/PTEN/protein kinase B (AKT) pathway mediates the effects of SPAG6 on cell proliferation and apoptosis, and the results demonstrated that silencing of SPAG6 suppressed the viability of Daudi and Raji cells, whereas PTEN knockdown using siRNA or SF1670 (a specific PTEN inhibitor) reversed the inhibitory effect on cell proliferation and the promoting effect on cell apoptosis induced by SPAG6 depletion in vitro as well as in vivo. These data revealed that SPAG6 may promote the proliferation and inhibit the apoptosis of BL cells via the PTEN/PI3K/AKT pathway. The results of the present study suggest that SPAG6 may play a key role in the progression of BL and may be of value as a predictive prognostic biomarker in patients with BL.

Risk Factors for Relapse of Childhood B Cell Acute Lymphoblastic Leukemia.

BACKGROUND B cell acute lymphoblastic leukemia (B-ALL) is the most common type of ALL. This study aimed to explore risk factors for relapse of childhood B-ALL. MATERIAL AND METHODS Total of 102 pediatric B-ALL patients were included in this study. B-ALL patients were divided into a relapse group and a non-relapse group. Chemotherapy-induced agranulocytosis time, fusion gene, and minimal residual disease (MRD) were assessed. White blood cell (WBC) count in peripheral blood and risk stratification were evaluated in newly-diagnosed patients. Kaplan-Meier plots were used to evaluate the correlation between risk factors and relapse rates. Multivariate analysis was performed with Cox proportional hazard model to estimate relative risk (RR), 95% confidence interval (95% CI), and hazard ratio (HR). Finally, 99 cases of B-ALL were included in this study. RESULTS There were significant differences between the relapse group and the non-relapse group in age (p=0.004), chemotherapy-induced agranulocytopenia (p=0.001), WBC count in peripheral blood of newly diagnosed patients (p=0.016), risk stratification (p=0.000), and MRD at 12th week (p=0.007). Age over 10 years, high-risk stratification, long period of agranulocytopenia, higher WBC counts, and MRD more than 10⁻4 were correlated with higher B-ALL relapse rate (p<0.05). Multivariate analysis showed significantly higher relapse rates for age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻4, with RR (95% CI) of 4.001 (1.005-15.930), 4.964 (1.050-23.456), and 4.646 (1.383-15.614), respectively. CONCLUSIONS Agranulocytopenia ≤7 days, peripheral blood WBC >100×109/L, and MRD at 33rd day >10⁻4 were associated with B-ALL relapse. Age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻4 were independent risk factors for relapse.

[Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis].

OBJECTIVE: To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. METHODS: Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. RESULTS: The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). CONCLUSION: The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

LncRNA SOX2 overlapping transcript acts as a miRNA sponge to promote the proliferation and invasion of Ewing's sarcoma.

Long non-coding RNAs (lncRNAs) function as critical regulator in human cancers. However, the biological regulatory mechanisms of lncRNAs in Ewing's sarcoma are still elusive. This study tries to investigate the clinical significance and pathological role of lncRNA SOX2 overlapping transcript (SOX2OT) in Ewing's sarcoma progression. SOX2OT was identified to be up-regulated in Ewing's sarcoma tissue and cells. In vitro, SOX2OT knockdown suppressed Ewing's sarcoma cells proliferation and invasion, and triggered apoptosis. In vivo xenograft assays, SOX2OT knockdown significantly inhibited Ewing's sarcoma growth. With the help of bioinformatics analysis and luciferase assay, SOX2OT was validated to harbor miR-363, acting as miRNA sponge or competing endogenous RNA (ceRNA). Furthermore, FOXP4 was validated to be the target protein of miR-363. Western blot and RT-PCR confirmed that SOX2OT was positively correlated with FOXP4 protein via sponging miR-363, forming a negative cascade regulation. In conclusion, our study realizes that SOX2OT acted as oncogene in the tumorigenesis of Ewing's sarcoma, suggesting the SOX2OT/miR-363/FOXP4 pathway in Ewing's sarcoma.

Fractional Exhaled Nitric Oxide (FeNO) Combined with Pulmonary Function Parameters Shows Increased Sensitivity and Specificity for the Diagnosis of Cough Variant Asthma in Children.

BACKGROUND Cough variant asthma in children presents with a dry nonproductive cough. This study aimed to investigate the diagnostic value of fractional exhaled nitric oxide (FeNO) combined with small airway functional parameters in cough variant asthma. MATERIAL AND METHODS Children with asthma (n=136) were divided into a cough variant asthma (CVA) group (n=57; mean age, 8.03±2.1 years) and a non-cough variant asthma (nCVA) group (n=79; mean age, 8.61±1.7 years). In both groups, FeNO and other pulmonary function parameters were measured including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF), forced expiratory flow (FEF), and maximum expiratory flow at 25%, 50%, and 75% expired volume (MEF25, MEF50, and MEF75). Receiver-operating characteristic (ROC) curve analysis compared the sensitivity and specificity between the diagnostic parameters. RESULTS The FeNO values were significantly increased in the CVA group compared with the nCVA group (Z=6.890, p<0.001). The MMEF, MEF25, MEF50, and MEF75 values were significantly lower in the CVA group compared with the nCVA group (p=0.000, p=0.014, p=0.000, and p=0.000, respectively). The FeNO values were negatively correlated with MEF25, MEF50, and MMEF (ρ=-0.334, ρ=-0.257 and ρ=-0.276, respectively). FeNO was significantly more efficient diagnosing cough variant asthma comparing with pulmonary parameters (p<0.05), and was most sensitive and specific when combined with MMEF/MEF50 compared with single diagnostic parameters (p<0.05). CONCLUSIONS FeNO combined with pulmonary function parameters of MMEF/MEF50 showed increased sensitivity and specificity for the diagnosis of cough variant asthma.

Retracted: Long Noncoding RNA SOX2OT Accelerates the Carcinogenesis of Wilms' Tumor Through ceRNA Through miR-363/FOXP4 Axis.

REFERENCES: ATCC. www.lgcstandards-atcc.org/Products/All/CRL-1441.aspx?geo_country=it Memorial Sloan Kettering Cancer Cancer. https://www.mskcc.org/research-advantage/support/technology/tangiblematerial/sk-nep-1-human-ewing-sarcoma-cell-line.

Juglanin suppresses fibrosis and inflammation response caused by LPS in acute lung injury.

Acute lung injury in children is a complication showing devastating disorders linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for acute lung injury. Juglanin is a natural product mainly isolated from green walnut husks of Juglans mandshurica, which isconsidered as the functional composition among a series of compounds. It exhibited effective role in various diseases by inhibiting inflammation response. In our study, the protective effects and anti-inflammatory activity of juglanin were investigated in mice and lung cells treated by lipopolysaccharide (LPS) to reveal the possible mechanism by which juglanin attenuates acute lung injury. The mice were separated into four groups. The mouse model was established with 15 mg/kg LPS injection. Juglanin dramatically reduced the inflammation of cell infiltration. Compared to mice only treated with LPS, LPS-treated mice in the presence of juglanin developed less lung fibrosis with lower levels of α-smooth muscle-actin (α-SMA), collagen type I, collagen type III, and transforming growth factor-ß1 (TGF-ß1). Additionally, juglanin markedly downregulated inflammatory cytokine secretion and phosphorylated nuclear factor-κB (NF-κB) expression via inhibiting IKKα/IκBα signaling pathway. Our results indicate that juglanin has a protective role in LPS-triggered acute lung injury via suppression of fibrosis and inflammation response by NF-κB signaling pathways inactivation. Thus, juglanin may be a potential candidate as dietary supplement for acute lung injury for children in future.

Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Ιnhibition by ST1926.

Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been well developed and investigated in clinical trials for many diseases. The aim of our study was to explore the role of ST1926 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to reveal the possible molecular mechanism. Mice were treated with LPS to induce acute lung injury followed by ST1926 administration. After LPS induction, mice administered with ST1926 showed lower inflammation infiltration in bronchoalveolar lavage (BAL) fluid, and pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-18, IL-6 and tumor necrosis factor-α (TNF-α) in serum and lung tissue samples obtained from mice. In addition, western blot assays suggested that ST1926 suppressed nuclear factor-κB (NF-κB), inhibitor-κB kinase-α (IκBα) and IκB kinase (IKKα), as well as Toll-like receptor 4 (TLR4) induced by LPS. In addition, reactive oxygen species (ROS) stimulated by LPS was also suppressed for ST1926 through inhibiting p38 and extracellular receptor kinase (ERK) signaling pathway. Taken together, the data here indicated that ST1926 may be of potential value in treating acute lung injury through inflammation and ROS suppression via inactivating TLR4/NF-κB and p38/ERK1/2 signaling pathways.

Benefits of urethroplasty for managing urethral amyloidosis: A case report.

Urethral amyloidosis is a rare condition in which eosinophilic amyloid proteins are deposited in the urethra. Only a small number of reports on urethral amyloidosis have been published. Increased interest has been associated with this disease due to its clinical similarities with urothelial carcinoma. A biopsy of the lesion and a histological examination are essential for the correct diagnosis. Conservative management has been suggested by various urologists as the optimal treatment approach for urethral amyloidosis; however, recurrence and urethral stricture are common, and typically further treatment is required. Urethroplasty has been used in a limited number of urethral amyloidosis cases, with beneficial short-term outcomes; however, long-term follow-up data are lacking. The present case report describes the cases of 2 patients with urethral amyloidosis who underwent urethroplasty without recurrence or progression for >2 years. These findings indicate that urethroplasty is beneficial for the long-term management of urethral amyloidosis.

Decreased expression of microRNA-122 is associated with an unfavorable prognosis in childhood acute myeloid leukemia and function analysis indicates a therapeutic potential.

MicroRNA (miR)-122 functions as a tumor suppressor in various human cancers. However, its involvement in childhood acute myeloid leukemia (AML) remains unknown. In this study, quantitative real-time PCR assay demonstrated that miR-122 expression in bone marrow specimens from AML children were significantly lower than that in non-malignant controls (P<0.001). Statistically, AML children with low miR-122 expression more frequently had large white blood cell count (P=0.022), French-American-British classification subtype M7 (P<0.001), unfavorable cytogenetics (P=0.002) and day 7 response to the treatment (P=0.036), short relapse-free (P=0.001) and overall (P=0.008) survivals than those with high expression. Multivariate analysis also determined that miR-122 expression was an independent prognostic factor for both relapse-free and overall survivals. Functionally, the enforced expression of miR-122 in AML cell lines efficiently suppressed cell proliferation and reduced the ratio of S-phase cells in vitro (all P<0.05). In conclusion, the abnormal expression of miR-122 may be a marker of the aggressive progression in childhood AML. Importantly, its downregulation may serve as a prognostic factor to predict poor outcome. Our study also reveal that miR-122 may function as a tumor suppressor in childhood AML, highlighting a new therapeutic strategy for this malignancy.

MicroRNA-183 promotes cell proliferation via regulating programmed cell death 6 in pediatric acute myeloid leukemia.

PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). METHODS: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined. RESULTS: miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 (P = 0.01) and unfavorable karyotypes (P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines. CONCLUSION: Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy.

Bakkenolide A inhibits leukemia by regulation of HDAC3 and PI3K/Akt-related signaling pathways.

Leukemia has been the third type of cancer killing many people across the world. Bakkenolide A (Bak), extracted from Petasites tricholobus, has been suggested to against cancer and display protective effects on inflammatory cytokines formation. And increasing evidences suggest that histone deacetylase 3 (HDAC3) plays vital roles in cancer formation and persistence via cell death, apoptosis and inflammation. But the function of Bakkenolide A in regulating leukemia is not understood yet, particularly via HDAC3. Here, we found that HDAC3 is up-regulated in clinical samples of leukemia compared with adjacent normal tissues. Then the expression of HDAC3 was knocked down via RNA interference in K562 cells. And inhibition of HDAC3 expression is able to improve leukemia invasion, migration and proliferation. Further, we also found HDAC3 bound to IκBα, affecting subsequent inflammation response. Moreover, Bakkenolide A was found to inhibit inflammation, induce apoptosis and cell death in leukemia cells via PI3K-regulated signaling pathway, down-regulating IKKs expression and suppressing in proinflammatory cytokines of IL-1ß, IL-18 and TNF-α. Up-regulation of Caspase3/7 was observed in cells of HDAC3-knockdown and Bakkenolide A treatment, inducing leukemia cell apoptosis. Also, the expression of Akt and GSK were activated by HDAC3-knockdown and Bakkenolide A-treatment. Thus, these results indicated that Bakkenolide A-mediated HDAC3 sensitization in leukemia cells seem to be associated with activation of effector IKKs, Akt/GSK, and caspases through induction of the PI3K pathway, leading to inflammation, cell death, and apoptosis.

Shenfu injection attenuates neonatal hypoxic-ischemic brain damage in rat.

Perinatal hypoxia-ischemia remains the most important cause of brain injury in the newborn. However, there is still no effective cure for neonatal hypoxic-ischemic brain damage (HIBD). In the present study, we aimed to examine the neuroprotective effects of Shenfu injection (SFI) on HIBD of neonatal rat. Sprague-Dawley rats were divided randomly into three groups (n = 8): S group: the rats were sham operated; C group: the rats were operated for HIBD modeling and received intraperitoneal injection of saline; SFI group: the rats were operated for HIBD modeling and received intraperitoneal injection of SFI (10 ml/kg days) for 7 days. Flow cytometry analysis showed that apoptosis rate of neuron in hippocampal CAI region in SFI group was significantly less than in NC group at 3 and 7 days after HI insult (P < 0.05). Immunohistochemical staining demonstrated that Bcl-2 expression was markedly higher while Bax expression was significantly lower in SFI group than in the C group at 24, 72 h and 7 days after HI insult (P < 0.05). Our findings suggest that SFI exhibits neuroprotective effects for neonatal hypoxic-ischemic brain injury by preventing neuron apoptosis and has potential to be used in the clinical for the treatment of perinatal hypoxia-ischemia.