Pancreatic Cancer, Leptin, and Chemoresistance: Current Challenges

Pancreatic cancer (PC) remains a leading cause of cancer-related deaths. Currently, conventional chemotherapies have showed only limited benefits for PC patients. Main factors affecting PC treatment failures are due to late detection, lack of early symptoms and biomarkers, and the development of desmoplasia and chemoresistance. Various mechanisms have been implicated in PC chemoresistance that includes stem cells, epigenetic changes, and alteration of signaling pathways, among others. Obesity is a modifiable factor for PC risk, which is characterized by high levels of the adipokine leptin that is a proinflammatory, proangiogenic, survival factor that affects chemotherapy effectiveness. Here, we will discuss on the mechanisms of PC chemoresistance and the influence of obesity and leptin signaling. Furthermore, the potential use of nontoxic leptin antagonists as a novel sensitization strategy for PC chemotherapeutics will also be discussed

Empowered Stakeholders: Female University Students’ Leadership During the COVID-19-Triggered On-campus Evictions in Canada and the United States

The study of disaster-specific leadership of female university students has been largely neglected, especially during on-campus emergency eviction and evacuation. Based on the COVID-19-triggered, on-campus evictions across Canada and the United States, this cross-national partnership examined the out-of-province/state and international female university students’ leadership during the entire eviction process. Through in-depth interviews, this study revealed the female university students’ leadership behaviors during three stages: (1) pre-eviction: their self-preparedness formed an emotional foundation to support others; (2) peri-eviction: their attitude and leadership behavior enabled them to facilitate (psychologically and physically) their peers’ eviction process; and (3) post-eviction: they continued to support their peers virtually and raised the general public’s awareness regarding the plight of vulnerable and marginalized populations. This article argues that the female university students’ leadership that emerged during the eviction process became complementary to and even augmented the universities’ official efforts and beyond. This leadership represents empirical evidence that contributes to the existing literature on gender and leadership by demonstrating female youth as empowered stakeholders rather than as merely passive victims. Future studies could develop detailed stratification of gender and age dimensions in order to portray a more comprehensive picture of the younger generation’s leadership in hazards and disaster research and practice

An Improved Method for the Isolation of Total RNA from Avicennia germinans Leaves

Isolation of high-quality RNA of Avicennia germinans L. tissue is difficult due to high levels of phenols and other substances that interfere when using conventional procedures for the isolation. These substances not only decrease the yield but also the quality of RNA is almost poor. We present here a simple RNA protocol and fast methodology that effectively removes these contaminating substances without affecting the yield. The protocol developed is based on the SDS/phenol method with modifications including -mercaptoethanol to prevent oxidation of phenolic complexes, and phenol/chloroform extraction is introduced to remove proteins, genomic DNA, and secondary metabolites, and co-precipitated polysaccharides. Both A 260 /A 230 and A 260 /A 280 absorbance ratios of isolated RNA were around 2 and the yield was about 0.3 mg g Ð1 fresh weight. Good-quality total RNA from leaves of Avicennia germinans could be easily isolated within 2 h by this protocol which avoided the limitation of plant materials and could provide total RNA for all kinds of further molecular studies

Group key exchange protocols withstanding ephemeral-key reveals

When a group key exchange protocol is executed, the session key is typically extracted from two types of secrets; long-term keys (for authentication) and freshly generated (often random) values. The leakage of this latter so-called ephemeral keys has been extensively analyzed in the 2-party case, yet very few works are concerned with it in the group setting. We provide a generic {group key exchange} construction that is strongly secure, meaning that the attacker is allowed to learn both long-term and ephemeral keys (but not both from the same participant, as this would trivially disclose the session key). Our design can be seen as a compiler, in the sense that it builds on a 2-party key exchange protocol which is strongly secure and transforms it into a strongly secure group key exchange protocol by adding only one extra round of communication. When applied to an existing 2-party protocol from Bergsma et al., the result is a 2-round group key exchange protocol which is strongly secure in the standard model, thus yielding the first construction with this property

Phytotoxic and dissuasive activity of Chihuahua desert plants

With the purpose of finding plant compounds with the potential use as herbicides and insecticides, a research was realized with the objective of evaluate the phytotoxic and dissuasive activity of four Chihuahua desert plants. The phytotoxic activity evaluation was tested on Lactuca sativa and Lolium perenne, while the dissuasive activity was realized on three species of phytophagous insects: Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis. Raw extracts were used, the solvents hexane, methanol and ethanol of different plants’ organs (root, steam, leaf and flower) of four species: Fouquieria splendens (ocotillo), Larrea tridentate (governor), Astragalus mollissimus (wild grass) and Pachycereus pecten-aboriginum (echo), by the establishment of in vitro bioassays at a concentration of 10 mg/ml extract/solvent. In the toxicity bioassay, the percentage of germination, root and leaf length were measured. The results showed that the leaf extract of L. tridentata had phytotoxic activity for L. sativa, while for L. perenne the phytotoxicity was observed within the ocotillo, governor and echo extracts. In the dissuasive bioassay, each treatment had 20 repetitions with 10 adult insects per repetition. The methanolic extracts of F. splendens leaf and root, ethanolic extract of A. mollisimus sheet and the ethanolic extract of P. pecten-aboriginum stems showed moderate dissuasive response of feeding against M. persicae, presenting a settlement inhibition index of 53.53, 54.35, 60.00 and 48.84% respectively. Nevertheless, the results indicated that none of the 10 extracts tested on S. littoralis showed significant dissuasive properties for this Lepidoptera, while for R. padi all the tested extracts presented dissuasive properties. The treatments of the four vegetable species evaluated showed defensive or dissuasive properties of moderate to strong feeding against the insects M. persicae and R. padi, presenting interesting potential for being used as insecticides, while the tested extracts that presented phytotoxicity for both lettuce and ryegrass present possibilities for the realization of herbicides

Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture

It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America

Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

<p>Abstract</p> <p>Background</p> <p>Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity.</p> <p>Results</p> <p>We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells.</p> <p>Conclusions</p> <p>Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.</p

Non-Invasive Assessment of Pulmonary Vasculopathy

Right heart catheterization remains necessary for the diagnosis of pulmonary hypertension and, therefore, for the prognostic evaluation of patients with chronic heart failure. The non-invaSive Assessment of Pulmonary vasculoPathy in Heart failure (SAPPHIRE) study was designed to assess the feasibility and prognostic relevance of a non-invasive evaluation of the pulmonary artery vasculature in patients with heart failure and pulmonary hypertension. Patients will undergo a right heart catheterization, cardiac resonance imaging, and a pulmonary function test in order to identify structural and functional parameters allowing the identification of combined pre- and postcapillary pulmonary hypertension, and correlate these findings with the hemodynamic dataThis research was funded by European Regional Development Fund and the Carlos III Research Institute through a grant of the Health Strategy Action (PI17/01569).S

Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug-Induced Liver Injury in the Spanish DILI Registry

Background and Aims: Drug-induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti-HEV seroprevalence rate. Methods: An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti-HEV Immunoglobulin (Ig) G antibodies were analyzed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n=144), HEV antigen (Ag) and anti- HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT-PCR was performed externally in 8 patients. Results: Out of 144 patients, 12 (8%) were positive for anti-HEV IgM, mean age 61 years. Underlying hepatic diseases (OR=23.4, p20 folds upper limit of normal (OR=10.9, p=0.002) were associated with the diagnosis of acute hepatitis E. The overall anti-HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). Conclusions: HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels.The present study has been supported by grants of the Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional FEDER (contract numbers: FIS PI0274-2016, PI-0285- 2016, PI 18-01804, PI 18-00901, PT17/0017/0020, CM17/00243, JR16/00015, B-0002-2019, UMA-18-FEDERJA-193 and by the Agencia Española del Medicamento. SCReN and CIBERehd are funded by Instituto de Salud Carlos III. European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, IMI2-Translational Safety Biomarker Pipeline (TransBioLine). The funding sources had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the manuscript for publicatio

MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.</p> <p>Results</p> <p>Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.</p> <p>Conclusions</p> <p>This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.</p