Toonasindiynes A-F, new polyacetylenes from Toona sinensis with cytotoxic and anti-inflammatory activities.

The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.

miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway.

Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA) approved by the FDA for the treatment of different kinds of cancers, especially colorectal cancer. Although the anti-tumor effects have been verified, the side effects of BVZ are also noteworthy, among which, cardiotoxicity may be the most serious side effect of BVZ. However, the exact mechanisms of cardiotoxicity induced by BVZ have been little explored. This study was conducted in vitro in a human cardiac myocyte (HCM) model. MTT assay was conducted to determine BVZ-stimulated cell viability. For testing the function and mechanism, the cells were transfected with miR-140-5p mimics, miR-140-5p inhibitor and/or VEGFA small interfering RNA (si-VEGFA). Then, apoptosis of the cells was detected via annexin V/propidium iodide (AV-PI) staining followed by flow cytometry. qRT-PCR and western blot assays were applied to measure gene expression (i.e. mRNA) and protein levels, respectively. The CK, LDH, SOD, CAT and GSH-Px activities and MDA level were determined using commercial kits. ROS levels were determined by DCFH-DA assay. Mitochondrial membrane potential was measured by JC-1 assay. Dual-luciferase reporter assay was used to detect the interaction between miR-140-5p and VEGFA. BVZ could inhibit HCM proliferation and induce apoptosis. miR-140-5p was upregulated in response to BVZ treatment and miR-140-5p restraint could alleviate HCM damage caused by BVZ treatment. In contrast, VEGFA and 14-3-3γ expressions were down-regulated by BVZ, and miR-140-5p could inhibit the expression of 14-3-3γ by directly targeting VEGFA. Moreover, VEGFA suppression enhanced HCM injury stimulated by BVZ and partially reversed the functional role of the miR-140-5p inhibitor in BVZ-treated cells. Taken together, miR-140-5p promoted BVZ-treated cardiomyocyte toxicity by targeting the VEGFA/14-3-3γ signal pathway. Collectively, miR-140-5p mediated the BVZ-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway, indicating that miR-140-5p may be a novel target for treating BVZ-induced cardiotoxicity.

New triterpenoids with diverse side-chains from the barks of Melia Toosendan.

Nine new euphane- and apotirucallane-type triterpenoids (Toosendines A-I; 1-9), along with three known tirucallane-type compounds were isolated from the barks of Melia toosendan. Their structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and circular dichroism spectra. Results of bioactivities screening exhibited that compounds 1, 4 and 5 showed remarkable NO inhibitory activities in LPS-activated RAW 264.7 macrophages, meanwhile, compounds 1 and 4 showed moderate cytotoxicities against U2OS human cancer cell line.

Primary Thyroid Extranasal NK/T-Cell Lymphoma Associated With Good Outcome: A Case Report and Literature Review: A Care-Compliant Article.

Most thyroid lymphomas are B-lineage, and T-cell lymphomas are rare. None of primary thyroid extranasal NK/T-cell lymphoma (NKTCL) has been reported in the literature. Here, we report a case of extranasal NKTCL exclusively arising in the thyroid in an 18-year-old Chinese.The patient presented with rapid anterior swelling at the neck and aggravated dyspnea for 2 months. Neck computer tomography scan revealed diffuse thyroid enlargement in the left lobe compressing the trachea. The thyroid function test was indicative of hypothyroidism. Gastroscopy demonstrated chronic nonspecific gastritis. Subtotal thyroidectomy was performed. Histological examination showed a diffuse infiltration of neoplastic lymphoid cells with an angiodestructive behavior. Immunophenotype is positive for CD2, CD56, CD43, and TIA-1, and typically negative for surface CD3. Epstein-Barr virus-encoded small RNAs were detected in tumor cells. A diagnose of primary thyroid extranasal NKTCL-N lymphoma was confirmed by the findings.The patient was treated with CHOP-L combination chemotherapy followed by local radiotherapy, and tolerated the modality well. The patient has been in remission for 28 months so far.To our knowledge, this is the first case report of primary extranasal NKTCL exclusively arising in the thyroid. The case has a relatively good treatment outcome with timely diagnosis and multimodality approach.

Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro.

5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.

Urologic and reproductive health status of 30 - 60 years old males: investigation among 1006 men in Shijingshan District of Beijing / 中华男科学杂志

<p><b>OBJECTIVE</b>To know and find some evidence for the improvement of the urologic and reproductive health of men between 30 and 60 years old.</p><p><b>METHODS</b>Using stratified random sampling, we conducted a questionnaire investigation on the urologic and reproductive health status of 1 006 men aged from 30 to 60 years old in the Shijingshan District of Beijing, including the unemployed, taxi drivers and office workers.</p><p><b>RESULTS</b>Of the 1006 males investigated, BMI > or = 24 kg/m2 was found in 72.7%, hypertension in 40.0%, abnormal IPSS in 85.5%, abnormal NIH-CPSI in 75.6%, abnormal IIEF-5 in 66.3%, aging male symptoms (AMS) in 10.7%, anxiety in 17.1%, depression in 25.1%, fasting blood-glucose >6.1 mmol/L in 34.9%, total cholesterol >5.07 mmol/L in 44.3% and triglyceride > 1.71 mmol/L in 46.6%; the level of total testosterone was (17.9 +/- 7.2) nmol/L, < 12 nmol/L in 21.3% and <8 nmol/L in 3.4%, and the level of free testosterone was (6.5 +/- 15.1) pmol/L.</p><p><b>CONCLUSION</b>The urologic and reproductive health status of 30 to 60 years old males in Beijing deserves serious attention from medical workers.</p>

Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.</p><p><b>METHODS</b>One hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.</p><p><b>RESULTS</b>Patients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.</p><p><b>CONCLUSIONS</b>Benazepril has a protective effect on mild to moderate impairment of renal function during coronary angioplasty. It is safe to use benazepril for treatment of patients with mild to moderate impairment of renal function before coronary intervention.</p>

Correlation of lower urinary tract symptoms with erectile dysfunction in men aged 50 years and above / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men aged > or = 50 years and to achieve the correlation between LUTS (obstructive symptoms and stimulant symptoms) and ED.</p><p><b>METHODS</b>We investigated 245 men aged > or = 50 years and with regular sex mates using International Prostate Symptom Score (IPSS) and International Index of Erectile Function-5 (IIEF-5), designed diagnostic interrogation and medical examination, and statistically analyzed the results of IPSS, IIEF-5, LUTS and their correlation with erectile function.</p><p><b>RESULTS</b>The incidence of ED was 81.9% (140/171) among the men with LUTS, 73.1% (38/52), 82.1% (46/56) and 88.9% (56/63) respectively in the 50-59, 60-69 and > or = 70 age groups, with significant differences in IPSS, IIEF-5 (P < 0.01) and the severity of ED (P < 0.01) among different age groups. ED incidence was found significantly correlated with the severity of LUTS (r = 0.52, P < 0.01), 71.3% (57/80), 89.6% (60/67) and 95.8% (23/24) respectively in the groups of mild, moderate and severe LUTS. The mean scores on obstructive and stimulant symptoms were (3.1 +/- 3.6) and (6.8 +/- 4.9), and their correlation coefficients with IIEF-5 were r = -0.41 (P < 0.01) and r = -0.59 (P < 0.01), respectively.</p><p><b>CONCLUSION</b>The incidence of ED is high in men with LUTS and positively correlated with the severity of LUTS. Stimulant symptoms have greater influence than obstructive symptoms on the sexual life of old and middle-aged males.</p>

[Expression and clinical significance of Survivin and Livin in DukesoB colorectal cancer].

BACKGROUND & OBJECTIVE: Survivin and Livin, members of the family of inhibitor of apoptosis proteins (IAPs), are specially expressed in embryonic cells and tumor cells, but are seldom expressed in normal adult cells. Some studies showed that they are correlated to poor prognosis of some tumors. This study was to detect the expression of Survivin and Livin in DukesoB colorectal cancer, and analyze the clinical significance. METHODS: The expression of Survivin and Livin in 81 specimens of DukesoB colorectal cancer and 12 specimens of normal colorectal tissues was detected by SP immunohistochemistry. Their correlations to clinical features and survival were analyzed. RESULTS: The positive rates of Survivin and Livin were significantly higher in colorectal cancer than in normal colorectal tissues (58.0% vs. 16.7%, 45.7% vs. 8.3%,P < 0.05). No relationship was found between the expression of Survivin and Livin(P > 0.05). The expression of Survivin and Livin was not correlated to sex, tumor location, primary size, T stage, pathologic category, and degree of differentiation(P> 0.05). The positive rate of Survivin was significantly higher in the patients older than 50 years than in the patients younger than 50 years (70.6% vs. 36.7%, P < 0.05). Both Survivin and Livin were correlated to tumor recurrence and/or metastasis (P = 0.02, P = 0.001), and shorter survival (P = 0.039, P = 0.001). Cox multivariate analysis showed stage T4 and positive Livin expression were independent prognostic factors of DukesoB colorectal cancer (P = 0.002, P = 0.047). CONCLUSIONS: Survivin and Livin are overexpressed in DukesoB colorectal cancer. Livin is closely related to recurrence and/or metastasis and poor prognosis of DukesoB colorectal cancer after curative resection.

[Study of TRAIL receptors expression on the mononuclear cells from multiple myeloma patients and KM3 cells].

OBJECTIVE: To study the differential expression of four TRAIL receptors on bone marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma cell line KM3 cells, to compare their altered expressions after chemotherapy and to explore the mechanisms by which TRAIL selectively kills tumor cells. METHODS: Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to investigate the expression of four TRAIL receptors on BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their expression pattern after chemotherapy and after incubation of KM3 cells with sub-clinical concentration of doxorubicin. RESULTS: DR4 and DR5 were highly expressed on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower than that of controls (P < 0.05). The expression of DR5 on MM and KM3 cells was up-regulated after chemotherapy and exposure to doxorubicin (P < 0. 05). CONCLUSIONS: The expressions of four TRAIL receptors on myeloma cells and normal controls were different, which might account for the selective killing effect of TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance the apoptosis of MM cells.