Enhanced and persistent levels of interleukin (IL)‐17+CD4+ T cells and serum IL‐17 in patients with early inflammatory arthritis

Prognosis of patients with early inflammatory arthritis (EIA) is highly variable. The aim of this study was to compare, longitudinally and cross-sectionally, the levels of cytokine-expressing cells in peripheral blood (PB) from patients with EIA to those in established rheumatoid arthritis (RA) and healthy controls (HC). PB mononuclear cells from HC (n = 30), patients with EIA (n = 20) or RA (n = 38) were stimulated with phorbol myristate acetate (PMA)/ionomycin for 3 h, and stained for cell markers and cytokines. Serum cytokines and chemokines were measured by Luminex. Patients with EIA were reassessed at 6 and 12 months. The percentage of interleukin (IL)-17⁺interferon (IFN)-γ⁻CD4⁺ T cells [T helper type 17 (Th17)] was increased in RA and EIA versus HC. Serum IL-1β, IL-2, IL-4 IL-17 and macrophage inflammatory protein (MIP)-1α were increased in RA and EIA versus HC. IL-1Ra, IL-15 and IFN-α were increased in EIA versus HC. IL-6 and tumour necrosis factor (TNF)-α was increased in RA but not EIA versus HC. Disease activity scores in EIA patients improved over 12 months'' treatment. Th17 percentage at baseline was correlated with both rheumatoid factor (RF) titre and functional deficit at 12 months. Baseline levels of serum granulocyte–macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-8 were correlated with Larsen score at 12 months. There were no significant changes in cytokine-expressing CD4⁺T cells over time, although the percentage of IL-6⁺ monocytes increased. IL-17⁺CD4⁺ T cells and serum IL-17 levels are increased in EIA. IL-6-expressing monocytes increase during the first year of disease, irrespective of disease-modifying anti-rheumatic drug (DMARD) therapy. We observed incomplete clinical responses, suggesting EIA patients need more intensive early therapy.     

Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?

Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.     

Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery

PURPOSE: To compare the efficacy of stimulation of P6 acupoint with capsicum plaster in comparison with iv ondansetron for the prevention of postoperative nausea and vomiting (PONV). METHODS: 120 patients of either sex, ASA I-II, undergoing elective middle ear surgeries under general anesthesia were included in this randomized, prospective, double-blinded and placebo-controlled study. The anesthetic technique was standardized. Patients were divided into three groups. Group I was the control group. Capsicum plaster (1 x 1 cm) was affixed at the P6 acupoint on both forearms 30 min before induction of anesthesia in patients of Group II. Patients of Groups I and III received an inactive adhesive plaster at the same site. Ondansetron 4 mg iv was given to patients of Group III at the end of surgery and the rest of the patients received a placebo. The plasters were removed six hours after transferring the patients to the postoperative unit. Criteria were fixed for the administration of rescue antiemetics (ondansetron 4 mg iv). PONV and the requirement for rescue antiemetics were recorded by a blinded observer. RESULTS: The incidence of PONV and the requirement for rescue antiemetics were significantly lower in both the acustimulation and ondansetron groups at six hours. At 24 hr there was a reduction in the requirement for rescue medication in the ondansetron group. CONCLUSION: Stimulation of the P6 acupoint with capsicum plaster is an effective method for prevention of PONV after middle ear surgery and its efficacy is comparable to ondansetron for the first six hours after surgery.     

Protective efficacy and the recovery profile of certain chemoprotectants against lethal poisoning by microcystin-LR in mice.

The cyclic peptide toxins microcystins and nodularins are the most common and abundant cyanotoxins present in diverse water systems. They have been the cause of human and animal health hazards and even death. Development of suitable chemoprotectants against microcystin is essential considering the human health importance. In the present study, three agents cyclosporin-A (10mg/kg), rifampin (25mg/kg) and silymarin (400mg/kg) pre-treatment gave 100% protection against lethal dose of microcystin-LR (100 microg/kg). Various biochemical parameters were evaluated to study the recovery profile of protected animals at 1, 3, 7 and 14 days post-toxin treatment. There was significant depletion of hepatic glutathione in protected animals compared to control group till 7 days post-treatment but normalised by 14 days. Similarly enhanced hepatic lipid peroxidation, inhibition of protein phosphatase activity was observed till 3-7 days post-treatment in protected animals. Elevated levels of enzymes alanine amino transferase, lactate dehydrogenase and sorbitol dehydrogenase were observed in serum at 1 day post-treatment. All the biochemical variables reached control levels by 14 day post-treatment. Immunoblotting analyses of liver homogenates showed microcystin-protein phosphatase adduct in liver samples of toxin treated as well as antidote-protected animals. The adduct could be seen even after 14 days post-toxin treatment. The study shows that though cyclosporin-A, rifampin and silymarin could offer 100% protection against microcystin-LR induced lethality many of the toxic manifestations are persistent and could not be reversed till 7 days.     

ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation,Regenerative Proliferation,and Poor Prognosis

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Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential

Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter between 150 and 200 nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), those are markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP were also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP were more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.