Application of triangular duct in solar-assisted air-heating system with surface roughness: a numerical investigation.

The device called solar air heater (SAH) is used to collect and transfer solar-thermal energy to air that can further be used for space heating, drying, etc. The conventional air heater (solar-assisted) has poor performance, and with this work, an attempt has been made to improve its performance by providing surface roughness over the heated surface. The roughness employed over the surface has an elliptical cavity, and its distribution over the heated surface is defined with the three parameters (dimensionless): relative flow-wise distance (ranging from 6 to 14), relative cavity depth (ranging from 0.016 to 0.038), and relative crosswise distance (ranging from 6 to 14). A CFD code has been developed and validated with experimentation to do the parametric study for understanding the effect of the proposed surface roughness on the performance of the air heater. It is concluded that the proposed surface roughness promotes the local turbulence, flow separation, and strong vortices in the flow field resulting in comparatively higher thermal performance in the proposed air heater. But this higher thermal performance is achieved at the expense of higher-pressure loss in the passage. A substantial change in heat augmentation by 2.57 times (with 2.3 times higher pressure loss) which results in 1.75 times higher thermo-hydraulic performance has been noticed over conventional designs at a relative flow-wise distance of 10, relative cavity depth 0.038, and relative crosswise distance of 10.

Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype.

Pancreatic cancer is a highly metastatic tumor with an extremely low 5-year survival rate. Lack of efficient diagnostics and dearth of effective therapeutics that can target the cancer as well as the microenvironment niche are the reasons for limited success in treatment and management of this disease. Cell invasion through extracellular matrix (ECM) involves the complex regulation of adhesion to and detachment from ECM and its understanding is critical to metastatic potential of pancreatic cancer. To understand the characteristics of these cancer cells and their ability to metastasize, we compared human pancreatic cancer cell line, PANC-1 and its invading phenotype (INV) collected from transwell inserts. The invasive cell type, INV, exhibited higher resistance to Carbon-ion radiation compared to whole cultured (normally dish-cultured) PANC-1 (WCC), and had more efficient in vitro spheroid formation capability. Invasiveness of INV was hampered by nitric oxide synthase (NOS) inhibitors, suggesting that nitric oxide (NO) plays a cardinal role in PANC-1 invasion. In addition, in vitro studies indicated that a MEK-ERK-dependent, JAK independent mechanism through which NOS/NO modulate PANC-1 invasiveness. Suspended INV showed enhanced NO production as well as induction of several pro-metastatic, and stemness-related genes. NOS inhibitor, l-NAME, reduced the expression of these pro-metastatic or stemness-related genes, and dampened spheroid formation ability, suggesting that NO can potentially influence pancreatic cancer aggressiveness. Furthermore, xenograft studies with INV and WCC in NSG mouse model revealed a greater ability of INV compared to WCC, to metastasize to the liver and l-NAME diminished the metastatic lesions in mice injected with INV. Overall, data suggest that NO is a key player associated with resistance to radiation and metastasis of pancreatic cancer; and inhibition of NOS demonstrates therapeutic potential as observed in the animal model by specifically targeting the metastatic cells that harbor stem-like features and are potentially responsible for relapse.

Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism.

SIGNIFICANCE: Cancer is a complex disease, which not only involves the tumor but its microenvironment comprising different immune cells as well. Nitric oxide (NO) plays specific roles within tumor cells and the microenvironment and determines the rate of cancer progression, therapy efficacy, and patient prognosis. Recent Advances: Key understanding of the processes leading to dysregulated NO flux within the tumor microenvironment over the past decade has provided better understanding of the dichotomous role of NO in cancer and its importance in shaping the immune landscape. It is becoming increasingly evident that nitric oxide synthase 2 (NOS2)-mediated NO/reactive nitrogen oxide species (RNS) are heavily involved in cancer progression and metastasis in different types of tumor. More recent studies have found that NO from NOS2+ macrophages is required for cancer immunotherapy to be effective. CRITICAL ISSUES: NO/RNS, unlike other molecules, are unique in their ability to target a plethora of oncogenic pathways during cancer progression. In this review, we subcategorize the different levels of NO produced by cells and shed light on the context-dependent temporal effects on cancer signaling and metabolic shift in the tumor microenvironment. FUTURE DIRECTIONS: Understanding the source of NO and its spaciotemporal profile within the tumor microenvironment could help improve efficacy of cancer immunotherapies by improving tumor infiltration of immune cells for better tumor clearance.

Understanding the tumour micro-environment communication network from an NOS2/COX2 perspective.

Recent findings suggest that co-expression of NOS2 and COX2 is a strong prognostic indicator in triple-negative breast cancer patients. These two key inflammation-associated enzymes are responsible for the biosynthesis of NO and PGE2 , respectively, and can exert their effect in both an autocrine and paracrine manner. Impairment of their physiological regulation leads to critical changes in both intra-tumoural and intercellular communication with the immune system and their adaptation to the hypoxic tumour micro-environment. Recent studies have also established a key role of NOS2-COX2 in causing metabolic shift. This review provides an extensive overview of the role of NO and PGE2 in shaping communication between the tumour micro-environment composed of tumour and immune cells that in turn favours tumour progression and metastasis. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.

Cholic acid-based novel micellar nanoplatform for delivering FDA-approved taxanes.

AIM: To structurally modify our existing cholic acid (CA)-based telodendrimer (TD; PEG5K-CA8) for effective micellar nanoencapsulation and delivery of the US FDA-approved members of taxane family. MATERIALS & METHODS: Generation of hybrid TDs was achieved by replacing four of the eight CAs with biocompatible organic moieties using solution-phase peptide synthesis. Drug loading was done using the standard evaporation method. RESULTS: Hybrid TDs can generate micelles with narrow size distributions, low critical micelle concentration values (1-6 µM), better hematocompatibility and lack of in vitro cytotoxicity. CONCLUSION: Along with PEG5K-CA8, CA-based hybrid nanoplatform is the first of its kind that can stably encapsulate all three FDA-approved taxanes with nearly 100% efficiency up to 20% (w/w) loading.

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles.

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications. In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer.

Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates.

Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.

Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.

Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.

Giant aneurysmal bone cyst of the mandible: A case report and review of literature.

Aneurysmal bone cysts are rare benign lesions of bone tissue. They are composed of vascular spaces blood-filled and surrounded by fibrous tissue septa. They are considered as pseudo cysts because of lack of epithelial lining. Here, we describe a giant case of ABC in 12-year-old female child having a massive swelling over the right side of the mandible treated with segmental resection and reconstruction with a reconstruction plate. Case is also discussed with the review of literature.

Spindle cell lipoma.

Spindle cell lipomas (SCLs) are a group of benign lipogenic tumours, typically arising in the posterior neck, upper back and shoulder of elderly male patients. Approximately 80% of these tumours arise in characteristic location, but 20% arise in unusual locations, thereby making these cases more difficult to diagnose. We present a case of SCL occurring in the right periorbital region of a 14-year-old boy. The MRI was suggestive of possible malignancy. Diagnosis of neurofibroma was made on incisional biopsy. However, the histopathological and immunohistochemical analyses of the excised lesion confirmed the diagnosis of SCL.

The percutaneous compression plate versus the dynamic hip screw: a meta-analysis.

Intertrochanteric fractures are a significant orthopaedic burden. The aim of this study was to assess how the Percutaneous Compression Plate (PCCP) technique performs compared to the traditional dynamic hip screw (DHS). A meta-analysis of all head to head trials (1995-2006) comparing the two techniques was performed. Early mortality (< or = 1 year) was the major outcome of interest. Secondary outcomes of interest included operation time (minutes), blood transfusion requirements, post-operative infection and length of stay in hospital (days). There was a decreased trend in overall mortality in the PCCP group [CI 0.84, (0.48 to 1.47), Chi-square = 1.36, p = 0.51]. Similar trends favouring the PCCP technique were seen with the other outcomes. PCCP being a relatively new technique has the potential to become the gold standard in the repair of intertrochanteric hip fractures. However, owing to the limitations of this meta-analysis, a large randomised controlled trial is required.