Experimental Lymphatic Filariasis in Gerbils (Meriones Unguiculatus): Molecular Cloning and Expression of Gerbil Cytokines and Measurement of Cytokine Gene Expression During a Primary Infection of Brugia Pahangi.

Cytokines play an important role in regulation of T cell responses. Two T helper cell subsets have been identified in some species and are defined by their cytokine secretion profiles. Th1 cells produce IL-2 and IFN-$\gamma,$ whereas Th2 cells express IL-4, IL-5, and IL-10. Precursor T cells that express a mixture of these cytokines are considered Th0 cells. It is hypothesized that primary infections of Brugia pahangi in gerbils induce an initial Th0 or Th1 like response which with time becomes a Th2 like response. To test this dynamic parasitism induced shift in cytokine profile, it is necessary to measure the expression level of cytokines that differentiate the Th1 and Th2 responses. For this purpose, the full length cDNAs of gerbil IL-2, IL-4, IL-5, IL-10, IFN-$\gamma$ and HPRT were first isolated using cross-species PCR, inverse PCR or RACE and conventional PCR techniques. Subsequently, a competitive RT-PCR ELISA for quantitation of gerbil cytokine mRNAs was developed. Using this assay, the profile of gerbil cytokine response was measured during a primary infection of Brugia pahangi. Increased levels of IL-2, and IL-5 were seen during the initial stages of the infection at 14 to 28 days post-infection (DPI). An increase in IL-4 was first detected 28 DPI in renal lymph nodes and continued to increase during the infection. Increased levels of IL-10 were first seen in the spleen 56 DPI and in all tissues at 150 DPI. These initial results are in agreement with the hypothesis proposed. In addition to the development of this cytokine measuring method, gerbil IL-2 cDNA was expressed in both eucaryotic and procaryotic expression systems. Pure and functional recombinant gerbil IL-2 (gIL-2) was obtained using the pMAL procaryotic system. Further, neutralizing anti-gIL-2 antibodies were raised in rabbits. The immunological reagents produced plus the cytokine quantitation assay established make it possible to initially measure immunologic responses in the gerbil. These types of measurements will advance the understanding of immunologic and pathologic responses of filariasis, using the gerbil-Brugia model. These methodologies also will expand the usefulness of this unique laboratory animal, in studies of other diseases

Dramatic reduction of distant pancreatic metastases using local light activation of verteporfin with nab-paclitaxel

Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates

Quitting smoking and mortality : a population-based mortality case-control study in Hong Kong

Background: Our knowledge of the health benefits of quitting smoking is mainly derived from prospective cohort studies in developed countries/regions, but such evidence is scarce and urgently needed in developing countries/regions. Mortality case-control studies could be a quick and low cost alternative to cohort study design. Smoking-attributable mortality was estimated using mortality case-control studies, but the effects of quitting have not been reported. Evidence on whether the benefits of quitting can be observed in mortality case-control studies is needed. Objectives: 1. To critically review the methods used in previous mortality case-control studies. 2. To examine the association between quitting smoking and total- and cause-specific mortality in Hong Kong, using the Hong Kong LIfestyle and MORtality (HK LIMOR) data. 3. To analyse and compare the effects of using different definitions of cases and controls on the association between the health benefits of quitting and total- or cause-specific mortality using the HK LIMOR data. Methods: The HK LIMOR study, a large population-based case-control study, included 81% of all registered deaths at age 30+ years from all four Hong Kong death registries in 1998, with information on duration of quitting collected in the second half of the year. Different definitions of cases and controls were used in previous mortality case-control studies. The main analysis followed the definitions in Sitas et al 2013. Cases were deaths from diseases that could be affected by smoking (N=19,526); controls were deaths from all non-smoking related causes (N=6,076). Two other definitions (Liu et al 1998 and Alam et al 2013) were used for sensitivity analyses. Unconditional logistic regression was used to calculate adjusted odds ratios of total-cause and cause-specific mortality by smoking and quitting status, duration of quitting, and age at quitting, adjusting for sex and age at death. Results: 1. Mortality case-control study design was used to estimate smoking-attributable mortality only in developing regions, except Hong Kong. There were considerable variations in data collection methods and definitions of cases and controls. 2. Compared with continuing smokers, sex- and age-specific (middle age at death [35-64 years] and old age [65-94 years]) risk reductions from quitting were observed for total deaths of interest and 9 other smoking-related diseases. Dose-response relations across mortality risk reductions with quitting duration and age at quitting were found. 3. Varied definitions of cases and controls in mortality case-control studies yielded different results in middle age at death by quitting status, duration of quitting and age at quitting for total deaths of interest, lung cancer and cardiovascular disease mortality, but the results were similar in old age. Conclusion: The HK LIMOR is the first mortality case-control study that has shown health benefits (mortality risk reduction) of quitting smoking. Our results are consistent with the findings from cohort studies. In addition, the mortality case-control study design seems to be more practicable to estimate and monitor the harms of smoking and the benefits of quitting in both developed and developing regions.published_or_final_versionPublic HealthMasterMaster of Philosoph

Incidence of nasopharyngeal carcinoma and milk consumption : a worldwide ecological analysis

Background: Nasopharyngeal carcinoma (NPC) is a common malignancy in South Asia and North Africa. In recent years, NPC incidence is dramatically decreasing which cannot be explained by the current etiological factors. Moreover, milk consumption is promising as factor to be investigated and showed declining trend in worldwide. To our knowledge, there are no population level studies to examine the association between NPC and milk & dairy products consumption. Objective: The objective of this study was to investigate the relationship between NPC incidence and per capita consumption of milk at the population level. Methods: These were two types of ecological studies (cross-sectional and longitudinal ecological study). NPC incidence data were collected from Cancer Incidence in Five Continents Vol. IX (1998-2002) and several population-based cancer registries. Data of per capita consumption of milk & dairy were obtained from Food Agriculture Organization (FAO). Results: In cross-sectional ecological study, age-standardized incidence rate (ASIR) of NPC is negatively associated with per capita consumption of milk & dairy products in 48 countries/ regions from 1961 to 2009. Moreover, in one-way sensitivity analysis, the result was consistent with the above. In longitudinal ecological study from around 1980 to 2009, ASIR of NPC (both genders) was negatively correlated with milk consumption per capita in Hong Kong and Singapore. The ASIR of NPC (both genders) was decreased with per capita consumption of milk from around 40 to 140 kg/capita/year in Hong Kong and Singapore. Further, such negative associations were found statistically significantly between NPC and milk consumption in Hong Kong after adjusting for HDI. Conclusion: Our study provided information on the protective association between NPC and milk & dairy products. Our ecological study shows that higher per capita consumption of milk & dairy products is associated with a lower risk of NPC development. However, our finding need to future confirm since there are major limitations on data and methods. Further research is needed for confirmation of the link between milk consumption and NPC.published_or_final_versionPublic HealthMasterMaster of Public Healt

Tracking Photodynamic- and Chemotherapy-Induced Redox-State Perturbations in 3D Culture Models of Pancreatic Cancer: A Tool for Identifying Therapy-Induced Metabolic Changes

The metabolic plasticity of cancer cells is considered a highly advantageous phenotype that is crucial for disease progression and acquisition of treatment resistance. A better understanding of cancer metabolism and its adaptability after treatments is vital to develop more effective therapies. To screen novel therapies and combination regimens, three-dimensional (3D) culture models of cancers are attractive platforms as they recapitulate key features of cancer. By applying non-perturbative intensity-based redox imaging combined with high-throughput image analysis, we demonstrated metabolic heterogeneity in various 3D culture models of pancreatic cancer. Photodynamic therapy and oxaliplatin chemotherapy, two cancer treatments with relevance to pancreatic cancer, induced perturbations in redox state in 3D microtumor cultures of pancreatic cancer. In an orthotopic mouse model of pancreatic cancer, a similar disruption in redox homeostasis was observed on ex vivo slices following photodynamic therapy in vivo. Taken together, redox imaging on cancer tissues combined with high-throughput analysis can elucidate dynamic spatiotemporal changes in metabolism following treatment, which will benefit the design of new metabolism-targeted therapeutic approaches

Cross-species PCR cloning of gerbil (Meriones unguiculatus) interleukin-2 cDNA and its expression in COS-7 cells

A cDNA clone of the gerbil interleukin-2 (IL-2) gene was isolated by cross-species PCR cloning, and demonstrated to produce a functional gerbil IL-2 protein when inserted in the eucaryotic expression vector pSV-SPORT1 and transfected into COS-7 monkey cells. The open reading frame codes for a polypeptide of 155 amino acid residues with a molecular weight (MW) of 17 601 which includes a putative signal peptide. The mature gerbil IL-2 is deduced to contain 135 amino acid resides and has a calculated MW of 15 496. Culture supernatant of COS-7 cells transfected with pSV-SPORT1-GIL-2, but not pSV-SPORT1 stimulates the proliferation of the IL-2 dependent murine CTLL-2 cells. Molecular characteristics of gerbil IL-2 have been compared with IL-2 of mouse, rat, human, bovine, ovine and porcine origin. The mature form of gerbil IL-2 is similar in molecular weight to all species except the mouse. A N-glycoslation site present in bovine, ovine and porcine IL-2 respectively, is absent in gerbil. Three Cys residues are conserved in all compared mature IL-2 molecules. In these comparisons, gerbil IL-2 has highest identity with rat IL-2 for both nucleotide and amino acid sequence. © 1994

Cobalt Nanocluster-Doped Carbon Micro-Spheres with Multilevel Porous Structure for High-Performance Lithium-Sulfur Batteries

Lithium-Sulfur batteries (Li-S batteries) have gained great interest in next-generation energy storage systems due to their high energy density and low-cost sulfur cathodes. There is, however, a serious obstacle in the commercial application of Li-S batteries due to the poor kinetics of the redox process at the sulfur cathode and the “shuttle effect” caused by lithium polysulfide (LiPSs). Herein, we report the synthesis of a sulfur cathode host material that can drastically inhibit the “shuttle effect” and catalyze the conversion of LiPSs by a simple electrostatic spray technique, namely, cobalt (Co) nanoclusters doped with N-containing porous carbon spheres (Co/N-PCSs). The results show that Co/N-PCSs has catalytic activity for the transformation of liquid LiPSs to solid Li2S and alleviates the notorious “shuttle effect.” This new sulfur cathode exhibits stable running for 300 cycles accompanied by a capacity of 650 mAh g−1 at a current density of 1 C, a capacity fading rate of 0.051% per cycle, and a Coulombic efficiency maintained at close to 100%. The results demonstrate that Co/N-PCSs offers the possibility of practical applications for high-performance Li-S batteries

Nitrogen-Doped Porous Carbon Nanosheets Based on a Schiff Base Reaction for High-Performance Lithium-Ion Batteries Anode

Lithium-ion batteries (LIBs) have already gained significant attention because they have satisfactory energy density and no memory effect, making them one of the most widely used energy storage systems. In commercial LIBs, graphite is widely used as an anode material due to its excellent electrical conductivity and structural stability; however, as they are limited by their restricted theoretical capacity, there is an urgent need for the development of novel anode materials for LIBs. For this purpose, we designed a nitrogen-doped two-dimensional layered porous carbon material (2D-PNC) based on a covalent organic framework (COF) generated by a Schiff base reaction as a precursor. The characterization analysis results show that 2D-PNC is made of stacked two-dimensional ultra-thin carbon sheets with a porous structure. This unique structure is beneficial for electrolyte impregnation and lithium-ion storage, resulting in excellent electrochemical performance of 2D-PNC, which shows a high specific capacity of 573 mAh g−1 after 380 cycles at 0.5 A g−1. The results show that 2D-PNC provides the possibility of a practical application of high-performance lithium-ion batteries