A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.
Chromatography, High Pressure Liquid ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rutaceae ; chemistry ; Sesquiterpenes ; isolation & purification

A new phenethanol, (2'R)-4-(2', 3'-dihydroxy-3'-methyl-butanoxy)-phenethanol (1), along with other eleven known benzene derivatives (2-12) were isolated from the roots, stems and leaves of Clausena excavata (Rutaceae). Compounds 3 and 4 are new natural products, and compounds 5-8, 10-12 were isolated from C. excavata for the first time. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analyses including HSQC, COSY and HMBC experiments. 1 was tested for its cytotoxicities against A549, HeLa and BGC-823 cancer cell lines, and antimicrobial activities against Candida albicans and Staphylococcus aureus. The results showed that 1 did not exhibit cytotoxic and antimicrobial activities.
Benzene Derivatives ; chemistry ; Candida albicans ; drug effects ; Cell Line, Tumor ; Clausena ; chemistry ; HeLa Cells ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Staphylococcus aureus ; drug effects

One new dicyclopeptide cyclo-(L-N-methyl Glu-L-N-methyl Glu) (1), together with one new natural dicyclopeptide cyclo-(L-methyl Glu ester-L-methyl Glu ester) (2), and two known dicyclopeptides cyclo-(L-methyl Glu ester-L-Glu) (3), and cyclo-(L-Glu-L-Glu) (4), were isolated from the aerial parts of Dianthus chinensis L. Their structures were determined by spectroscopic analyses and chemical methods.
Dianthus ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

OBJECTIVETo screen the potential protein biomarkers in minimal residual disease (MRD) of the acute promyelocytic leukemia (APL) by comparison of differentially expressed serum protein between APL patients at diagnosis and after complete remission (CR) and healthy controls, and to establish and verify a diagnostic model.

METHODSSerum proteins from 36 cases of primary APL, 29 cases of APL during complete remission and 32 healthy controls were purified by magnetic beads and then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The spectra were analyzed statistically using FlexAnalysis(TM) and ClinProt(TM) software.

RESULTSTwo prediction model of primary APL/healthy control, primary APL/APL CR were developed. Thirty four statistically significant peptide peaks were obtained with the m/z value ranging from 1000 to 10 000 (P < 0.001) in primary APL/healthy control model. Seven statistically significant peptide peaks were obtained in primary APL/APL CR model (P < 0.001). Comparison of the protein profiles between the two models, three peptides with m/z 4642, 7764 and 9289 were considered as the protein biomarker of APL MRD. A diagnostic pattern for APL CR using m/z 4642 and 9289 was established. Blind validation yielded correct classification of 6 out of 8 cases.

CONCLUSIONSThe MALDI-TOF MS analysis of APL patients serum protein can be used as a promising dynamic method for MRD detection and the two peptides with m/z 4642 and 9289 may be better biomarkers.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Child ; Humans ; Leukemia, Promyelocytic, Acute ; classification ; diagnosis ; Male ; Middle Aged ; Neoplasm, Residual ; classification ; diagnosis ; Prognosis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Young Adult

PURPOSE: Obstructive ileocolitis is an ulcero-inflammatory condition which typically occurs in the ileum or colon proximal to an obstructing colorectal lesion. If left unresolved, it often leads to intestinal perforation. We present a matched case control study of patients with obstructive ileocolitis caused by colorectal cancer to determine if any factors can predict this condition. METHODS: This is a retrospective review of 21 patients with obstructive colorectal cancer and histologically proven obstructive ileocolitis from 2005 to 2015 matched for age and sex with 21 controls with obstructing colorectal cancer without obstructive ileocolitis. RESULTS: The 21 patients with obstructive ileocolitis had a median age of 71 years (range, 52–86 years). The most common presenting symptom was abdominal pain (n = 16, 76.2%), followed by vomiting/nausea (n = 14, 66.7%) and abdominal distension (n = 12, 57.1%). Interestingly, the radiological feature of pneumatosis intestinalis was noted in only 1 case. No significant differences were observed in baseline comorbidities, clinical presentations, or tumor characteristics between the 2 groups. Patients with obstructive ileocolitis were found to have a significantly higher total leucocyte count (17.1 ± 9.4×109/L vs. 12.0 ± 6.8×109/L, P = 0.016), lower pCO2 (32.3 ± 8.2 mmHg vs. 34.8 ± 4.9 mmHg, P = 0.013), lower HCO3 (18.8 ± 4.5 mmol/L vs. 23.6 ± 2.7 mmol/L, P < 0.001), lower base excess (-6.53 ± 5.32 mmol/L vs. -0.57 ± 2.99 mmol/L, P < 0.001) and higher serum lactate levels (3.14 ± 2.19 mmol/L vs. 1.19 ± 0.91 mmol/L, P = 0.007) compared to controls. No radiological features were predictive of obstructive ileocolitis. CONCLUSION: Patients with obstructive ileocolitis tend to present with metabolic acidosis with respiratory compensation, raised lactate, and worse leucocytosis. Radiological features are not useful for predicting this condition.
Abdominal Pain ; Acidosis ; Case-Control Studies* ; Colon ; Colorectal Neoplasms* ; Comorbidity ; Compensation and Redress ; Crohn Disease* ; Humans ; Ileum ; Intestinal Obstruction ; Intestinal Perforation ; Lactic Acid ; Retrospective Studies

Objective To investigate risk factors for the progress of subclinical atherosclerosis (AS)in newly diagnosed type 2 diabetics with muhifactorial intervention.Methods One hundred and fifty- six patients of type 2 diabetes,aged 35～70 years,with course of less than one year and without subclinical AS,were observed prospectively.After two-year intervention based on anti-platelet therapy integrated with intensive control of blood glucose,blood lipid,blood pressure and body weight,dynamic changes in all metabolic indicators and subclinical AS in the patients and differences between those with subclinical AS and without it were analyzed to study the risk factors for its progress by logistic regression analysis.Results There were no significant differences in intima-medial thickness(IMT)of common carotid artery(CCA) and femoral artery(FA)in the patients between baseline and two years after intervention,but those in them were significantly increased two years after intervention than those one year after intervention(P＜0.O1). Two years after intervention,increased IMT or atherosclerotic plaques could be found in 45 of 156 patients (28.8%),significantly higher than those one year after intervention(11.5%,P＜0.01).Levels of glycosylated hemoglobin Alc(HbAlc),total cholersterol(TC),high-density lipoprotein-cholesterol (HDL-C)and HOMA-insulin resistance(IR)showed an increased trend two years after intervention,as compared with those one year after intervention(P＜0.01).Proportions of those with normal level of HbAlc two years after intervention was significantly lower than that one year after intervention(P＜0.01). Proportions of those with normal level of HbAlc and low-density lipoprotein-cholesterol(LDL-C)were significantly lower in patients with subclinical AS than those without it two years after intervention(P＜0.01).Logistic regression analysis showed that relative risk(RR)for subclinical AS could reduce by 83% with normal level of LDL-C and 59% by normal HbAlc,respectively,but there was an 82% increase in RR for it with an increase of age by ten years.Conclusions Subclinical AS could not be absolutely prevented in patients with newly diagnosed type 2 diabetics after two-year intensive multifactorial intervention.Subclinical AS could present a progressive trend with time,as well as levels of blood glucose and blood lipid.Levels of LDL-C and HbAlc,as well as age,were major risk factors for occurrence of subclinical AS in patients with newly-diagnosed type 2 diabetes.

OBJECTIVETo investigate the association between expressions of HSP70, HSP90 and efficacy of chemotherapy in colorectal cancer patients with unresectable liver metastasis.

METHODSData of 52 colorectal cancer cases, whose primary colorectal focuses were resected but hepatic metastatic tumors were unresectable, were reviewed retrospectively. All the patients underwent FOLFOX4 regimen well. Immunohistochemistry assay was applied to determine the expressions of HSP70 and HSP90 in primary focus tissues. The number and size of hepatic metastatic tumors pre- and post-chemotherapy were compared by CT scanning.

RESULTSPartial remission(PR) rate was 33.3% in cases with up-regulated expression of HSP70, while 64.5% in cases with down-regulated expression of HSP70, whose difference was significant. PR rate was 50% in cases with up-regulated expression of HSP90, and 53.1% in the others with down-regulated expression of HSP90, whose difference was not significant.

CONCLUSIONSFOLFOX4 regimen has advantages in cases with lower HSP70 expression over those with higher HSP70 expression. HSP90 expression level is not associated with the efficacy of FOLFOX4 regimen.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; secondary ; Male ; Middle Aged ; Prognosis ; Treatment Outcome

OBJECTIVETo explore the toxicity of joint exposure to diazinon, propoxur and bisphenol A on phagocytosis.

METHODSFlow cytometer was employed to detect the influence of diazinon and bisphenol A, propoxur and bisphenol A in mixture (mixed according to ratio of IC(50)) on mouse macrophage RAW264.7 cells' function to phagocyte fluorescent microspheres, adopting the percentage of phagocytic cells (PP) and the phagocytic index (PI) as measurement indicators. The final concentrations of mixture of diazinon and bisphenol A were (0.4 + 0.1), (3.6 + 0.7), (36.2 + 7.2), (43.4 + 8.7), (52.1 + 10.4), (62.5 + 12.5), (75.0 + 15.0) µg/ml; while those of mixture of propoxur and bisphenol A were (0.2 + 2.0 × 10(-2)), (2.4 + 0.2), (23.7 + 2.0), (35.6 + 3.0), (53.3 + 4.4), (80.0 + 6.7), (120.0 + 10.0) µg/ml. Then based on the dose-response relationship, a 2 × 2 factorial design was then carried out among different doses of mixture with statistical significance to statistically evaluate the interaction between diazinon and bisphenol A, propoxur and bisphenol A.

RESULTSAfter the joint exposure, compared to the control group (PP = (23.6 ± 2.2)%; PI = 0.36 ± 0.03), any dose of the mixture of diazinon and bisphenol A ((52.1 + 10.4), (62.5 + 12.5), (75.0 + 15.0) µg/ml) could significantly increase the levels of PP ((29.0 ± 1.4)%, t = 3.89, P < 0.05; (30.2 ± 2.3)%, t = 4.74, P < 0.05; (35.0 ± 3.4)%, t = 8.21, P < 0.05) and PI (0.43 ± 0.03, t = 3.86, P < 0.05; 0.41 ± 0.02, t = 2.95, P < 0.05; 0.46 ± 0.03, t = 5.34, P < 0.05); while that of propoxur and bisphenol A ((35.6 + 3.0), (53.3 + 4.4), (80.0 + 6.7), (120.0 + 10.0) µg/ml) reduced the levels of PP ((20.6 ± 1.1)%, t = -3.00, P < 0.05; (20.2 ± 1.0)%, t = -3.42, P < 0.05; (19.4 ± 1.3)%, t = -4.23, P < 0.05; (18.8 ± 2.1)%, t = -4.81, P < 0.05) and PI (0.31 ± 0.01, t = -4.75, P < 0.05; 0.31 ± 0.01, t = -4.58, P < 0.05; 0.30 ± 0.01, t = -4.92, P < 0.05; 0.27 ± 0.02, t = -7.80, P < 0.05) on the contrary. The 2 × 2 factorial design was carried out between the mixture of diazinon (60.0 µg/ml; PP = (28.5 ± 3.4)%; PI = 0.49 ± 0.07) and bisphenol A (12.0 µg/ml; PP = (35.7 ± 2.7)%; PI = 0.67 ± 0.07), and the mixture of propoxur (48.0 µg/ml ; PP = (28.1 ± 2.2)%; PI = 0.48 ± 0.04) and bisphenol A (4.0 µg/ml; PP = (34.4 ± 2.7)%; PI = 0.59 ± 0.07). The mixture of diazinon and bisphenol A (PP = (30.4 ± 1.4)%, F(interaction) = 6.22, P < 0.05; PI = 0.53 ± 0.03, F(interaction) = 7.35, P < 0.05) and the mixture of propoxur and bisphenol A (PP = (27.5 ± 4.1)%, F(interaction) = 4.56, P < 0.05; PI = 0.46 ± 0.08, F(interaction) = 11.13, P < 0.05) both showed a significant antagonistic interaction on phagocytosis of RAW264.7 cell.

CONCLUSIONIt is suggested that the interactions between diazinon & bisphenol A and propoxur & bisphenol A both played the antagonistic role on phagocytic function of macrophages in vitro.

Animals ; Benzhydryl Compounds ; Cell Line ; Diazinon ; toxicity ; Drug Synergism ; Environmental Exposure ; Macrophages ; cytology ; drug effects ; Mice ; Phagocytosis ; drug effects ; Phenols ; toxicity ; Propoxur ; toxicity

OBJECTIVETo establish a new method for the preparation of porcine acellular dermal matrix.

METHODSThe antigenicity of the porcine dermis was weakened by removing epidermal and dermal cells from the porcine skin through the digestion with low-concentration trypsin and repeated freeze-thaw cycles. Split thickness porcine skin was treated with 0.05% trypsin to remove the cells from the epidermis and dermis. Repeated freeze-thaw cycles were employed to further weed out the residual cells within the dermis. The prepared acellular dermis was then examined grossly, as well as histologically, and also by immunohistochemical method.

RESULTSNo cell could be identified in the prepared porcine acellular dermal matrix. The integral basement membrane was preserved on the surface of dermal matrix with compact dermal matrix collagen structure.

CONCLUSIONLow concentration trypsinization and repeated freeze-thaw cycles seemed to be a simple and effective method for the preparation of xenogeneic acellular dermal matrix.

Animals ; Dermis ; cytology ; transplantation ; Extracellular Matrix ; transplantation ; ultrastructure ; Freezing ; Skin Transplantation ; Swine ; Tissue Engineering ; methods ; Trypsin ; administration & dosage