Oxysophocarpine suppresses TRAF6 level to ameliorate oxidative stress and inflammatory factors secretion in mice with dextran sulphate sodium (DSS) induced-ulcerative colitis.

PURPOSE: Ulcerative colitis is an inflammation-related disease with a high recurrence risk. Oxysophocarpine (OSC) is a traditional Chinese medicine isolated from legumes and exerts vital functions on many human diseases. However, the OSC's role in ulcerative colitis has not been fully elucidated. This research aimed to investigate the OSC's impact on ulcerative colitis and its mechanisms. METHODS: A mouse model of ulcerative colitis was induced by dextran sulphate sodium (DSS). The effect of OSC on ulcerative colitis was examined using Disease Activity Index detection, hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA). Meanwhile, the mechanism of OSC in ulcerative colitis was assessed by immunohistochemistry assay, Western blot, HE staining, and ELISA. RESULTS: For the OSC's function in ulcerative colitis, OSC increased the mice weight, decreased Disease Activity Index scores, and alleviated colitis cell infiltration and epithelial cell destruction in DSS-induced ulcerative colitis. Also, OSC mitigated oxidative stress (decreased PGE2, MPO levels, and increased SOD levels) and inflammation (decreased IL-6, TNF-α and IL-1ß levels) in DSS-induced ulcerative colitis. For the OSC's mechanism in ulcerative colitis, OSC inhibited the level of tumor necrosis factor receptor-associated Factor 6 (TRAF6) and the phosphorylation of nuclear factor-κB (NF-κB). TRAF6 overexpression abolished the effect of OSC on DSS-induced colon injury and its associated oxidative stress and inflammatory properties in ulcerative colitis. CONCLUSION: OSC decreased the TRAF6 level to reduce oxidative stress and inflammatory factors secretion in mice with DSS induced-ulcerative colitis.

Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes.

Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin-residing microbes are undefined. Here, we developed a one-step fluorogenic substrate, S-B, for specific detection of bacterial CDase activity and inhibitor screening. We identified a non-hydrolyzable substrate mimic, C6, as the best hit. Based on C6, we designed a photoaffinity probe, JX-1, which efficiently detects bacterial CDases. Using JX-1, we identified endogenous low-abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S-B and JX-1, we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing.

Studies on competitive adsorption characteristics of bisphenol A and 17α-ethinylestradiol on thermoplastic polyurethane by site energy distribution theory.

Compound pollution of microplastics and estrogens is a growing ecotoxicological problem in aquatic environments. The adsorption isothermal properties of bisphenol A (BPA) and 17α-ethinyl estradiol (EE2) on polyamide (TPU) in monosolute and bisolute systems were studied. Under the same adsorption concentration (1-4 mg L-1), EE2 had a greater adsorption capacity than BPA in the monsolute system. Compared to the energy distribution features of the adsorption sites of EE2 and BPA, the BPA adsorption sites were located in the higher energy area and were more evenly distributed than those of EE2, while the quantity of BPA adsorption sites was less than that of EE2. In the bisolute system, the average site energy, site energy inhomogeneity, and adsorption site numbers of BPA increased by 1.674, -17.166, and 16.793%, respectively. In comparison, the average site energy, site energy inhomogeneity, and adsorption sites numbers of EE2 increased by 2.267, 4.416, and 8.585%, respectively. The results showed that BPA and EE2 had a cooperative effect on the competitive adsorption of TPU. XPS analysis showed that BPA and EE2 had electron transfer on TPU, although the chemisorption effects and hydrogen bonds between BPA and TPU were more significant. Comparing the changes in the relative functional group content of TPU in monosolute and bisolute systems, BPA and EE2 were synergistically absorbed on TPU. This study can provide a theoretical reference for the study of competitive adsorption between coexisting organic pollutants.

[Correlation between Expression of CD47 Molecule in Patients with Newly Diagnosed Adult Acute Myeloid Leukemia and Clinical Prognosis].

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34+, CD38+, CD123+ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION: The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.

Effect of Alpina oxyphylla extract on streptozotocin-induced kidney injure via regulating TGF-ß1 and MyD88.

BACKGROUND: Abnormal renal metabolism is closely related to the development of chronic kidney disease. It is well known that renal inflammation plays an important role in the occurrence and development of tubulointerstitial damage in the renal tubules. The purpose of the experiment was to observe the bioactivity of Alpina oxyphylla extract (AOE) on renal injury in diabetic nephropathy (DN) rats induced by streptozotocin (STZ). METHODS: Thirty male Wistar rats were randomly divided into five group (n = 6): (1) intact control (non-diabetic, ND); (2) intact diabetic (STZ), (3) diabetic rats treated with gliclazide 5 mg/kg (STZ-gli), (4) diabetic rats treated with AOE 400 mg/kg (AOE 400), (5) diabetic rats treated with AOE 800 mg/kg (AOE 800). The diabetic nephropathy rat model was established by single intraperitoneal injected 50 mg/kg STZ. Fasting blood glucose (FBG) and body weight was observed at 1、3、6 weeks. After 6 weeks, the renal function parameters of five groups and 24 h urinary protein were detected. Expression of transforming growth factor-beta1 (TGF-ß1) and myeloid differentiation factor 88 (MyD88) were assessed by Western Blot. RESULTS: The STZ group showed hyperglycemia, proteinuria, renal function damage, and the levels of 24 h urinary protein, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and interleukin-6 (IL-6) in the STZ group increased significantly compared with the ND group. The expression of TGF-ß1 in STZ group was increase (p < 0.01), and the expression of MyD88 was significantly lower than in ND group (p < 0.05). The treatment of DN rats with AOE attenuated DN-associated in the serum biochemical index and the expression of TGF-ß1. CONCLUSIONS: AOE can effectively protect kidney tissues of diabetic nephropathy, and probably through regulating level of TGF-ß1/MyD88.

Aluminum-induced "mixed" cell death in mice cerebral tissue and potential intervention.

The brain is one of organs vulnerable to aluminum insult. Aluminum toxicity is involved in neurobehavioral deficit, neuronal cell dysfunction, and death. The aim of this study are as follows: (1) to evaluate the repairing efficiency of Necrostatin-1 (Nec-1), a cell death inhibitor, and Z-VAD-FMK, a pan-caspase inhibitor, on Al-induced neurobehavioral deficit and neuronal cell death, in order to evidence the cell death inducing ability of aluminum, and (2) to primarily explore the possibility of treating neuronal cell loss-related disease, such as Alzheimer's disease, with Nec-1 and Z-VAD in Al-induced dementia animal model. We found Nec-1 and Z-VAD-FMK alone or in combination could reduce aluminum-induced learning and memory impairment in mice. Pathohistological results indicated that Nec-1 and Z-VAD-FMK can decrease Al-induced neuronal death cell. In addition, some cell death-associated proteins in cell death signal pathway were inhibited by Nec-1 and Z-VAD-FMK in Al-exposed mice. In conclusions, Nec-1 and Z-VAD-FMK can repair the injury of learning and memory induced by aluminum in mice. Furthermore, Nec-1 was more obvious to repair the injury of learning and memory function compared with Z-VAD-FMK. Nec-1 and Z-VAD-FMK can repair the Al-induced morphological injury of cell and reduce the amounts of dead cell, and repairing effects were more significant at higher doses. The effect of Nec-1 was stronger than Z-VAD-FMK, though their mechanism was different. The combination of them had the strongest effect. Our study evidenced Al-induced neuronal necroptosis and apoptosis existing in animal model and suggested potential therapeutic effects of Nec-1 and Z-VAD-FMK on neuronal cell death in neurodegenerative diseases.

Brønsted Base-Switched Selective Mono- and Dithiolation of Benzamides via Copper Catalysis.

A versatile protocol for the direct thiolation of an inert sp2 C-H bond is presented via a catalytic amount of copper catalysis, by switching related Brønsted bases and regulating the reaction time, and the corresponding mono- and dithiolation products can be obtained selectively in moderate to good yields. The reaction exhibits a relatively broad substrate scope and a good functional group tolerance, even with different heterocyclic amides and alkyl thiols.

Synthesis, structure, and anion binding of functional oxacalix[4]arenes.

Oxacalix[4]arenes obtained from the highly efficient, one-pot SNAr reaction were post-macrocyclization functionalized through the reduction of nitro groups and hydrolysis of the ester groups to obtain several derivatives of desired solubility. The difficulties in basic hydrolysis of ester groups were overcome via developing an acid hydrolysis method for tert-butyl ester derivatives of this class. The synthesis of symmetrical oxacalix[4]arenes from an unsymmetrically substituted precursor was also explored via a multiple step fragment coupling approach. Compounds 17 & 18 adopted 1,3-alternate conformations in the solid state as most oxacalix[4]arenes did, and a chair (zigzag) conformation was revealed for tetraamido oxacalix[4]arene (6a) by X-ray single crystal analysis. The tetraureido oxacalixarene (7) showed strong association towards various anions such as F-, Cl-, Br-, I-, Ac-, and HSO4- with a 1 : 1 stoichiometry as revealed by 1H NMR analysis and UV-vis measurements.

Synthesis of α-arylthioacetones using TEMPO as the C3 synthon via a reaction cascade of sequential oxidation, skeletal rearrangement and C-S bond formation.

Here, we present an unprecedented pathway to α-sulfenylated carbonyl compounds from commercially available thiols and universally employed TEMPO and its analogues, which act as C3 synthons through skeletal rearrangement under simple and metal-free conditions. Mechanism studies suggest that this reaction involves a consecutive radical oxidation and cation coupling process. TEMPO analogues and thiols serve as oxidants and reductive reagents, respectively, along the radical process, while in the coupling process, the former ones afford C3 synthons to couple with related sulfur sources.

Retinoblastoma Binding Protein 5 Correlates with the Progression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy tumors with insidious onset, rapid development and metastasis, and poor prognosis. Therefore, it is necessary to understand molecular mechanisms of HCC and identify clinically useful biomarkers for it. This study aimed to investigate the role of retinoblastoma binding protein 5 (RBBP5) in HCC. The expression level of RBBP5 was examined by immunohistochemistry and western blot. The effect of RBBP5 on cell cycle, proliferation, apoptosis, and drug sensitivity was analyzed. RBBP5 was significantly upregulated in HCC tissues and cells. High RBBP5 expression was significantly associated with elevated level of AFP, advanced TNM stage, high Ki-67 expression, larger tumor size, and poor prognosis. Knockdown of RBBP5 significantly inhibited proliferation of HCC cells through cell cycle arrest. In addition, inhibition of RBBP5 increased the sensitivity of HCC cells to doxorubicin. In conclusion, our findings suggest that RBBP5 plays an important role in the progression of HCC and may serve as a novel biomarker and potential therapeutic target for HCC.

KI-catalyzed C-S bond formation via an oxidation relay strategy: efficient access to various α-thio-ß-dicarbonyl compounds.

An efficient and practical methodology to obtain α-thio-ß-dicarbonyl compounds was presented under alkaline conditions via potassium iodide (KI) catalysis; various symmetrical/unsymmetrical 1,3-dicarbonyl compounds were obtained under an aerobic atmosphere in moderate to excellent yields, with good functional group tolerance. Notably, a widely used anti-inflammatory drug butazodine could be modified with our protocol, even on a gram scale.

Direct access to α-sulfenylated amides/esters via sequential oxidative sulfenylation and C-C bond cleavage of 3-oxobutyric amides/esters.

An efficient, environmentally benign and unprecedented synthesis of various α-sulfenylated amides/esters has been developed under oxygen atmosphere. The reaction shows good functional group tolerance and excellent chemo/regioselectivity. All the desired products were obtained in moderate to excellent yields, even on the gram scale. Practically, the related α-thiol Weinreb amide can be readily transferred to a series of prospective compounds, and selenium atom can be introduced to the α-sites of the amides in high yields.

An early superficial non-ampullary duodenal tumor cured with endoscopic submucosal dissection: A case report.

Early superficial non-ampullary duodenal tumors are particularly rare, the clinical manifestations, including typical endoscopic or imaging features, and treatment methods are not well-characterized. The present case report describes a case of an asymptomatic 74-year-old male who presented to the Taizhou People's Hospital (Taizhou, China) for a regular health screening, where a primary superficial non-ampullary duodenal tumor was identified. Upper endoscopy revealed ~1.2 cm lesion in the second portion of the duodenum. Chromoscopy and magnification endoscopy indicated an early cancer characteristic. Subsequent endoscopic submucosal dissection was performed to remove the lesion. Histopathology validated that the lesion was a high-grade intro-epithelial neoplasm without lymph node or blood vessel invasion.

Angiopoietin-like protein 3 is an indicator of prognosis in esophageal cancer patients.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in angiogenesis. This study aimed to examine the protein expression of ANGPTL3, and to evaluate its clinical significance in esophageal cancer. ANGPTL3 expression was detected using immunohistochemistry in 98 pairs of esophageal cancer and adjacent non-cancerous tissues. The expression levels of ANGPTL3 in esophageal cancer tissues were significantly higher than those in adjacent noncancerous tissues (P < 0.05). No association was observed between ANGPTL3 expression and clinical features (P > 0.05). Although ANGPTL3-negative patients had longer survival time than ANGPTL3-positive patients, the difference did not reach statistical significance (P = 0.090). Stratified analysis of ANGPTL3 expression according to clinical features revealed that there was significant association between ANGPTL3 expression and overall survival among patients aged 65 years or younger, female, or with lymph node metastasis (P < 0.05). When after adjusted for clinical features, the association remained significant only in patients aged 65 years or younger (P = 0.021).Taken together, our findings provide preliminary evidence of association of ANGPTL3 expression with the prognosis of subgroups of patients with esophageal cancer.

[Clinical analyses of fungal pleurisy: a report of 4 cases].

OBJECTIVE: To explore the clinical features of fungal pleurisy. METHODS: Four cases of fungal pleurisy diagnosed by medical thoracoscopy at Beijing Chaoyang Hospital from April 2005 to December 2012 were retrospectively studied. RESULTS: There were 3 males and 1 female with an age range of 43-73 years. The time from initial onset to definite diagnosis was 17 days to 4 months. Among them, two were previously healthy while another two had underlying diseases. The diagnoses were mucor pleuritis (n = 1) and aspergillus (n = 3). There was one case of empyema. One case was diagnosed as non-Hodgkin lymphoma two years ago and had pleural metastasis during hospitalization. And another one suffered concurrently from diabetes mellitus and hypoproteinemia. The primary clinical manifestations included fever (n = 2), cough and sputum (n = 3), breathlessness (n = 4) and weight loss (n = 2). The major chest computed tomography (CT) scan revealed pleural effusion with thickening. All cases had an elevated plasma level of C-reactive protein (CRP). The characteristics of pleural effusion were empyema (n = 1) and exudates (n = 3). Pleural fluid smear and culture tests for bacteria and fungi were negative, so were pleural fluid smear tests for mycobacteria. All cases were confirmed through histopathological examination of pleural biopsies and cured after systemic antifungal therapy and pleural irrigation. CONCLUSIONS: Fungal pleurisy is infrequent. Early thoracoscopy is vital because of a low positive yield of microbiologic testing of pleural fluid specimens. Systemic antifungal therapy and pleural irrigation improve the prognosis.

[Prevalence and psychopathological characteristics of anxiety and depression in patients with chronic rhinosinusitis before endoscopic sinus surgery].

OBJECTIVE: To investigate the prevalence and psychopathological characteristics of anxiety and depression in patients with chronic rhinosinusitis (CRS) and to find the risk factors leading to psychological problems. METHODS: Between August 2013 and April 2014, 117 consecutive patients with the diagnosis of CRS who had been scheduled for endoscopic sinus surgery were prospectively enrolled. Somatic and psychological symptoms were evaluated using a series of questionnaire instruments. The instruments included symptom checklist-90 (SCL-90), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and the visual analogue scale (VAS) and the sinonasal outcome test 20 (SNOT-20) and Lund-Mackay computed tomography score. The results of SAS, SDS, SCL-90 were compared with the standard, obtained from healthy Chinese population. Multivariate Logistic regression was used to analyze the factors that might cause anxiety and depression. SPSS 19.0 software was used to analyze the data. RESULTS: The scores of SAS and SDS (39.40 ± 11.55, 54.05 ± 10.96) were significantly higher than those of our country's normal standard (29.78 ± 10.46, 41.88 ± 10.57, t equals 5.648, 7.529, all P < 0.01). The SCL-90 scores were significantly higher than those of the normal standard population, including dimension of somatization, anxiety, depression, psychosis and total average score of the factors ( all P < 0.01), the result of somatization, anxiety, depression had positive correlation with the scores of SAS and SDS (r equals 0.681, 0.781, 0.531, 0.866, 0.674, 0.557, all P < 0.05). Multivariate Logistic regression showed that gender and CRS complicated with asthma or allergic rhinitis (AR) and the symptom of nasal obstruction were related to the incidence of anxiety depression comorbid. In addition, the gender and concurrent asthma had positive correlation with incidence of any anxiety or depressive disorder. To compare the abnormal psychological state group and healthy group, the SNOT-20 scores had no statistical significance (all P > 0.05). CONCLUSIONS: High prevalence of anxiety and depression was found in CRS patients. Such factors as gender, nasal obstruction and concurrent with asthma or AR are high risk factors for anxiety and depression in patients with CRS.

Caspase-3 short hairpin RNAs: a potential therapeutic agent in neurodegeneration of aluminum-exposed animal model.

There is abundant evidence supporting the role of caspases in the development of neurodegenerative disease, including Alzheimer's disease (AD). Therefore, regulating the activity of caspases has been considered as a therapeutic target. However, all the efforts on AD therapy using pan-caspase inhibitors have failed because of uncontrolled adverse effects. Alternatively, the specific knockdown of caspase-3 gene through RNA interference (RNAi) could serve as a future potential therapeutic strategy. The aim of the present study is to down-regulate the expression of caspase-3 gene using lentiviral vector-mediated caspase-3 short hairpin RNA (LV-Caspase-3 shRNA). The effect of LV-Caspase-3 shRNA on apoptosis induced by aluminum (Al) was investigated in primary cultured cortical neurons and validated in C57BL/6J mice. The results indicated an increase in apoptosis and caspase-3 expression in primary cultured neurons and the cortex ofmice exposed to Al, which could be down-regulated by LV-Caspase-3 shRNA. Furthermore, LV-Caspase-3 shRNA reduced neural cell death and improved learning and memory in C57BL/6J mice treated with Al. Our results suggest that LV-caspase-3 shRNA is a potential therapeutic agent to prevent neurodegeneration and cognitive dysfunction in aluminum- exposed animal models. The findings provide a rational gene therapy strategy for AD.

Upregulation of miR-301a correlates with poor prognosis in triple-negative breast cancer.

Identification of biomarkers is important not only for cancer diagnosis, prognosis and treatment, but also provides new insight into cancer biology. The aim of this study was to evaluate the clinical significance of miR-301a in patients with triple-negative breast cancer (TNBC). The expression level of miR-301a was examined by quantitative reverse transcription polymerase chain reaction in 118 pairs of TNBC and adjacent noncancerous tissues. The relationships between miR-301a expression and clinical features, and prognosis of patients with TNBC were analyzed. miR-301a was upregulated in cancer tissues compared with adjacent noncancerous tissues. Furthermore, the level of miR-301a was positively correlated with tumor size, depth of invasion, TNM stage and LNM. High miR-301a expression was significantly associated with larger tumor size and LNM. Multivariate analysis suggested that miR-301a expression was an independent prognostic factor for the survival of patients with TNBC, and the effect remained significant after further stratified by clinical features. In conclusion, miR-301a may be involved in the progression of TNBC and has strong potential to serve as a biomarker for the prognosis of TNBC.

Association of the expression of unc-51-Like kinase 1 with lymph node metastasis and survival in patients with esophageal squamous cell carcinoma.

Unc-51-Like Kinase 1 (ULK1) is regarded as a central role in autophagy. Although the details of how ULK1 triggers autophagy are obscure, the relationship between ULK1 expression and the diagnosis and prognosis of cancer patients may guide the clinical practice and scientific research. The aim of this study was to investigate and compare the expression level of ULK1 in 86 paired esophageal squamous cell carcinoma (ESCC) and paracancerous tissues, and to examine the effect of ULK1 expression on the prognosis of ESCC patients. ULK1 was primarily expressed in cytoplasm, but was rarely seen in nucleus. The levels of cytoplasmic ULK1 in ESCC tissues were higher than those in paracancerous tissue (P < 0.01) and significantly associated with lymph node metastasis (LNM) (P = 0.025). Survival analysis showed that patients with low expression of cytoplasmic ULK1 had worse survival time than those with high expression of cytoplasmic ULK1 (hazard ratio = 1.754, 95% confidence interval: 1.022-3.010, P = 0.041), which disappeared after adjustment for TNM stages and LNM (P = 0.319). In conclusion, ULK1 might play an important role in the occurrence and development of ESCC and represent a potential prognostic biomarker for ESCC patients. However, the precise impact of ULK1 on predicting the prognosis of patients with ESCC requires further investigation.