RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degradingthe components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the antiproliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, amajor target in several types of cancers, has not been studied. Powdered samples of various parts of A.muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependentinhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, theseextracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 likeREversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients notexposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtainedfrom normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. Thepresent study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-canceractivity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

Effect of short-term naturopathy and yoga intervention on anthropometric variables, lipid profile and thyroid profile in obese hypothyroid patients: a randomised controlled trial

Background: Hypothyroidism reflects decreased thyroid function and is one of the most common conditions seen in clinical practice. Practice of naturopathy and yoga has shown improvement in anthropometric variables and lipid profile in obesity and other chronic diseases. So, the aim of this study was to find out the effect of naturopathy and yoga in obese hypothyroid patients.Methods: A total of 60 subjects, of which 29 males (age 44.2±7.0 years) and 31 females (age 40.6±7.4 years) with body mass index (BMI), ?30 were randomly assigned to case group (n=30) and wait list control group (n=30). The subjects of case group underwent naturopathy and yoga intervention for 10 days. Anthropometric variables, viz., body weight, BMI, waist circumference (WC) and hip circumference, serum lipid profile, and serum thyroid profile were assessed at 1st day (pre), at the end of 10 day (post).Results: The result showed a significant reduction in body weight, BMI, WC, total cholesterol, low density lipoprotein-cholesterol (LDL-C) and thyroid stimulating hormone (TSH) along with significant improvement in high density lipoprotein-cholesterol (HDL-C) in case group compared with control group in independent samples t test. Significant reduction in body weight, BMI, total cholesterol, LDL-C and TSH were observed in case group unlike in control group in student's paired t test.Conclusions: Reduction in the body weight, BMI and improvement in serum lipid profile and serum thyroid profile in case group subjects compared to control group suggest that naturopathy and yoga have therapeutic and protective effects in the management of obese hypothyroid patients.

Design

According to one pot microwave assisted synthesis, the versatile precursor 2- aminothiazole was prepared and utilized for the construction of new thiazole hybrids targeting MCF7 cell lines. 2‐amino thiazole was condensed with corresponding aldehydes to yield Schiff’sbase (2) intermediates followed by the diazo coupling reaction furnished the designed hybrids(3) contains azo-methine and diazo linkages in its structures. The newly synthesizedcompounds were confirmed on the basis of IR and H1NMR spectral analytical data. All thesynthesized compounds were evaluated for their in-vitro cytotoxicity activity against MCF-7celllines using MTT assay method. The obtained results revealed the more promising compoundsof the synthesised series, 3B and 3H with CTC50 value of 17.77±0.31μg/ml, 17.83±1.14 μg/ml.

Effect of electro‑acupuncture, massage, mud, and sauna therapies in patient with rheumatoid arthritis.

A 48‑year‑old married woman diagnosed with rheumatoid arthritis (RA) in 2007, came to our hospital in July 2014 with the complaint of severe pain and swelling over multiple joints, especially over small joints, which was associated with stiffness (more in morning), deformities of fingers and toes, with disturbed sleep and poor quality of life (QOL) for the past 7 years. She received a combination of electro acupuncture (14 sessions), massage (18 sessions), mud (18 sessions), and sauna (3 sessions) (EMMS) therapies for 30‑min, 45‑min, 30‑min, and 15‑min per session, respectively for 3 weeks. During and postintervention assessment showed reduction in visual analog scale score for pain, Depression Anxiety and Stress Scales and the Pittsburgh Sleep Quality Index scores. It also showed an increase in the scores of 10‑Meter Walk Test, isometric hand‑grip test, and short form‑36 version‑2 health survey. This result suggest that, the EMMS therapy might be considered as an effective treatments in reducing pain, depression, anxiety, and stress with improvement in physical functions, quality of sleep and QOL in patient with RA. EMMS therapies were tolerated and no side effects were reported by the patient. Though the results are encouraging, further studies are required with larger sample size and advanced inflammatory markers.

Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells / 中西医结合学报

<p><b>OBJECTIVE</b>Deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, showed inhibition of the growth of various tumor cells in vitro. In the present study, we investigated the cytotoxicity and apoptosis-inducing capacity of deoxyelephantopin on lung adenocarcinoma (A549) cells.</p><p><b>METHODS</b>The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase-contrast microscopy. The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was also analyzed.</p><p><b>RESULTS</b>Deoxyelephantopin exhibited cytotoxicity to A549 cells (IC50 = 12.287 μg/mL), however, there was no toxicity towards normal human lymphocytes. Deoxyelephantopin suppressed the colony-forming ability of A549 cells in a dose-dependent manner. Acridine orange, ethidium bromide and Hoechst 33342 staining showed cell shrinkage, chromosomal condensation and nuclear fragmentation, indicating induction of apoptosis. Deoxyelephantopin increased apoptosis of A549 cells, as evidenced by more TUNEL-positive cells. DNA fragmentation and Annexin V staining revealed late-stage apoptotic cell population. Deoxyelephantopin inhibited A549 cell growth by cell cycle arrest at G2/M phase and induced apoptosis through both extrinsic and intrinsic pathways.</p><p><b>CONCLUSION</b>These results suggest that deoxyelephantopin has great potential as a new chemotherapeutic agent to be developed further for the treatment of lung cancer.</p>

Liver oxidative stress of the grey mullet Mugil cephalus presents seasonal variations in Ennore estuary

The objective of this study was to determine the liver oxidative stress status of grey mullets living in heavy-metal-rich polluted Ennore estuary compared with unpolluted Kovalam estuary. Fish were collected from both estuaries during the monsoon and summer seasons from October 2004 to September 2006. Fish liver homogenate (N = 20 per group) was prepared for evaluating oxidative stress parameters. Fish living in the polluted estuary had significantly higher lipid oxidation products, conjugated dienes (0.346 ± 0.017 vs 0.141 ± 0.012 DA233/mg protein), lipid hydroperoxides (0.752 ± 0.032 vs 0.443 ± 0.03 nmol/mg protein), and lipid peroxides (3.447 ± 0.14vs 1.456 ± 0.096 nmol MDA/mg protein) than those of the unpolluted estuary during the summer. In contrast, significantly lower levels of superoxide dismutase (20.39 ± 1.14 vs 53.63 ± 1.48 units/mg protein) and catalase (116 ± 6.87vs 153 ± 8.92 units/mg protein) were detected in the liver of fish from the polluted estuary (Ennore) compared to fish from the unpolluted estuary (Kovalam) during the summer. Variations in most of the oxidative stress parameters were observed between the summer and monsoon seasons, indicating the importance of seasonal variation for estuaries and their inhabitants.

Pulmonary functions in workers of fertiliser and chemical industry.

The present study was undertaken to assess the pulmonary functions in fertiliser and chemical industry workers of Kerala. Pulmonary function test was performed with Vitalograph Compact-II spirometer. Exposure to different chemicals, noxious gases and particulate matter of fertiliser and chemical industry was injurious to the normal pulmonary function. Significant decline in lung volumes, viz. FVC, FEV1, FEV1/FVC% (P < 0.01) and flow rates, viz. FEF25-75%, FEF0.2-1.2, FEF25%, FEF50%, FEF75% (P < 0.01) among non-smokers and smokers than that of normal controls was observed. The findings of this study also suggest that with increased duration of exposure to industrial pollutants, lung volumes and flow rates were significantly reduced in workers.

Hypoglycemic effects of leucodelphinidin derivative isolated from Ficus bengalensis (Linn).

A Leucodelphinidin derivative isolated from the bark of Ficus bengalensis Linn demonstrated hypoglycemic action at a dosage of 250 mg/kg given both in normal and alloxan diabetic rats. It's action is closely similar to that of an effective dose of glibenclamide (2 mg/kg) tested under the same conditions. However, after a glucose load the plant product is only just significantly active but not as effective as the sulphonylurea. The efficacy of the plant product as a hydroglycemic agent adds to its other therapeutic effects, as it belongs to the class of flavonoids.