Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

<p>Abstract</p> <p>Background</p> <p>Interleukin-12 (IL-12) is a cytokine well known for its role in immunity. A lesser known function of IL-12 is its role in hematopoiesis. The promising data obtained in the preclinical models of antitumor immunotherapy raised hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity, largely due to repeat dose regimens, and modest clinical response observed in the clinical trials have pointed to the necessity to design protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. We have focused on the lesser known role of IL-12 in hematopoiesis and hypothesized that an important clinical role for IL-12 in cancer may be as an adjuvant hematological cancer therapy. In this putative clinical function, IL-12 is utilized for the prevention of cancer therapy-related cytopenias, while providing concomitant anti-tumor responses over and above responses observed with the primary therapy alone. This putative clinical function of IL-12 focuses on the dual role of IL-12 in hematopoiesis and immunity.</p> <p>Methods</p> <p>We assessed the ability of IL-12 to facilitate hematopoietic recovery from radiation (625 rad) and chemotherapy (cyclophosphamide) in two tumor-bearing murine models, namely the EL4 lymphoma and the Lewis lung cancer models. Antitumor effects and changes in bone marrow cellularity were also assessed.</p> <p>Results</p> <p>We show herein that carefully designed protocols, in mice, utilizing IL-12 as an adjuvant to radiation or chemotherapy yield facile and consistent, multilineage hematopoietic recovery from cancer therapy-induced cytopenias, as compared to vehicle and the clinically-utilized cytokine granulocyte colony-stimulating factor (G-CSF) (positive control), while still providing concomitant antitumor responses over and above the effects of the primary therapy alone. Moreover, our protocol design utilizes single, low doses of IL-12 that did not yield any apparent toxicity.</p> <p>Conclusion</p> <p>Our results portend that despite its past failure, IL-12 appears to have significant clinical potential as a hematological adjuvant cancer therapy.</p

Life-cycle assessment approach for municipal solid waste management system of Delhi city

The life-cycle assessment (LCA) approach with route optimization technique was adopted in the present study to evaluate environmental and economic aspects associated with the prevalent waste management system in Delhi city. With an objective of cost minimization and abating environmental hazards from waste transportation systems, ArcGIS was used to identify the most appropriate route for waste transportation. The study was conducted considering four landfills located at Bawana, Bhalswa, Ghazipur and Okhla present in Delhi city. Landfilling, composting, anaerobic digestion, and recycling methods were analyzed for global warming potential (GWP), eutrophication potential (EP), acidification potential, abiotic resource depletion potential and photochemical oxidation potential parameters using LCA software GaBiPro. The results from the LCA studies for the municipal solid waste management system of Delhi city revealed that transportation emissions and landfilling negatively impact the environment. The effect of recycling rate on the landfilling, composting, anaerobic digestion was also studied using sensitivity analysis. Results of sensitivity analysis depicted that recycling of waste is inversely related to the impact categories. Overall, the results exhibited a detrimental effect of landfilling on the environment in terms of GWP and EP. Further, considering the geospatial analysis, two waste recycling stations are proposed in the vicinity of existing waste management plants to reduce the time and cost of waste transport from the landfills to the waste management plants. © 2022 Elsevier Inc

Evaluation of anti-diabetic activity of Nishamlaki on streptozotocin induced type II diabetic rats

Diabetes is a major health problem particularly in India. In spite of many drugs available, uncontrolled diabetes remains a challenge. Moreover, some of the antidiabetic drugs are on the verge of withdrawal due to adverse effects. So, there is an acute need for a new effective and safe drug. Present study was planned to evaluate anti-diabetic efficacy of Nishamalaki in diabetic wistar rats. Nishamalaki was prepared from powder of Curcuma longa and fresh juice of Emblica officinalis according to ayurvedic literature and administered with honey. Diabetes was induced in wistar rats by injection of 60 mg/kg of Streptozotocin and 110 mg/kg Nicotinamide IP. 30 rats showing blood glucose above 250 mg/dl were divided into 5 groups Group I(Control )-Saline, Group II(Control )- Vehicle honey, Group III – Nishamalaki Prophylactic, Group IV- Nishamalaki treatment &amp; Group V- Pioglitazone, given orally for 30 days. Blood glucose levels checked at days 0, 15, 30 &amp; Cholesterol on day 30. Nishamalaki treatment achieved significant (p&lt;0.01) lowering of blood glucose in diabetic rats comparable to that of the Pioglitazone treated group. Nishamalaki also reduced serum cholesterol levels. Antidiabetic efficacy of Nishamalaki in diabetic rats is comparable to Pioglitazone. It has also improved the lipid profile in diabetic rats

Exceptional anoxia resistance in larval tiger beetle, Phaeoxantha klugii (Coleoptera : Cicindelidae)

The tiger beetle Phaeoxantha klugii inhabits Central Amazonian floodplains, where it survives the annual inundation period in the third-instar larval stage submerged in the soil at approximately 29 degreesC for up to 3.5 months. Because flooded soils quickly become anoxic, these larvae should be highly resistant to anoxia. The survival of adult and larval P. klugii was therefore tested during exposure to a pure nitrogen atmosphere in the laboratory at 29 degreesC. Adult beetles were not resistant (< 6 h). Survival of larvae decreased over time, maximum survival was 15 days, whereas time to 50% mortality was 5.7 days (95% confidence interval 3.8-7.9). Anoxia resistance was additionally tested in third-instar larvae submerged within sediment for 40 days before anoxia exposure in the laboratory. Anoxia resistance was greatly enhanced in these larvae, showing a survival rate of 50% after 26 days of anoxia exposure. It appears that the gradual flooding process and/or the submersion phase induced a physiological alteration, most probably a strong depression in metabolic rate, which requires some days for induction. The degree of anoxia resistance in larval P. klugii is remarkable among terrestrial arthropods worldwide, even more so considering the high ambient temperatures. The species is well-suited to serve as a model organism for studying the physiological mechanisms of anoxia and submersion resistance in terrestrial arthropods inhabiting tropical floodplains

Determination of Iloperidone in Pharmaceuticals by Validated High-Performance Liquid Chromatography

WOS: 000416519900003Iloperidone is an antipsychotic drug used for treatment of acute schizophrenia in adults. In this study, a simple and specific method was developed for determination of iloperidone in tablets. The separation was performed on a C18 column using pH 3 20 mM phosphate buffer and acetonitrile as the mobile phase. The optimum conditions were 1 ml/min flow rate, 35 degrees C column temperature, and 2 mu L injection volume. Carbamazepine was used as an internal standard. Iloperidone was monitored at 274 nm with a diode array detector. The method was validated according to the literature guidelines and was linear from 0.5 to 100 mu g/ml of iloperidone. The detection and quantification limits were 0.0909 and 0.3030 mu g/ml, respectively. The method was acceptable in terms of accuracy, precision, specificity, robustness, and stability and employed for the analysis of tablets.Research Council of Anadolu University [1302S023]The authors thank Research Council of Anadolu University for the support of the Project (Project No: 1302S023)

A Cytokine-Delivering Polymer Is Effective in Reducing Tumor Burden in a Head and Neck Squamous Cell Carcinoma Murine Model

ObjectiveThis study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC).Study designIn vivo study.SettingAcademic research laboratory.Subjects and methodsMice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. For cytokine studies, mice were grouped into (1) no polymer, (2) plain polymer, (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week, (4) polymer containing parental dendritic cells, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21).ResultsThe cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P &lt; .01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P &lt; .01).ConclusionHerein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC