Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer)

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa

Metagenomic analysis unveils the microbial landscape of pancreatic tumors

The composition of resident microbes in the human body is linked to various diseases and their treatment outcomes. Although studies have identified pancreatic ductal adenocarcinoma (PDAC)-associated bacterial communities in the oral and gut samples, herein, we hypothesize that the prevalence of microbiota in pancreatic tumor tissues is different as compared with their matched adjacent, histologically normal appearing tissues, and these microbial molecular signatures can be highly useful for PDAC diagnosis/prognosis. In this study, we performed comparative profiling of bacterial populations in pancreatic tumors and their respective adjacent normal tissues using 16S rRNA-based metagenomics analysis. This study revealed a higher abundance of Proteobacteria and Actinomycetota in tumor tissues compared with adjacent normal tissues. Interestingly, the linear discriminant analysis (LDA) scores unambiguously revealed an enrichment of Delftia in tumor tissues, whereas Sphingomonas, Streptococcus, and Citrobacter exhibited a depletion in tumor tissues. Furthermore, we analyzed the microbial composition between different groups of patients with different tumor differentiation stages. The bacterial genera, Delftia and Staphylococcus, were very high at the G1 stages (well differentiated) compared with G2 (well to moderate/moderately differentiated) and G3/G4 (poorly differentiated) stages. However, the abundance of Actinobacter and Cloacibacterium was found to be very high in G2 and G3, respectively. Additionally, we evaluated the correlation of programmed death-ligand (PDL1) expression with the abundance of bacterial genera in tumor lesions. Our results indicated that three genera such as Streptomyces, Cutibacterium, and Delftia have a positive correlation with PD-L1 expression. Collectively, these findings demonstrate that PDAC lesions harbor relatively different microbiota compared with their normal tumor adjacent tissues, and this information may be helpful for the diagnosis and prognosis of PADC patients

Mold In Residences And The Associated Respiratory Diseases/Symptoms Among Occupants

Indoor mold may cause asthma and other respiratory symptoms; however, no study has been conducted in homes in Memphis. This study aims to monitor indoor mold exposure and explore its relationship to respiratory symptoms/illnesses. Environmental monitoring was conducted in 15 homes (9 with visible mold and 6 without) in Shelby County. Indoor environmental samples included ground and air vent dust, volatile organic compounds (VOCs), real-time particulate matter (PM), CO2, relative humidity (RH), and temperature. In laboratory, mold in dust samples were analyzed using an Endpoint PCR and VOCs on a thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) system. No association was found between detected and reported mold. Neither we found statistically significant association between environmental exposure and reported respiratory symptoms. These findings need to be confirmed by future studies with larger sample sizes and geographic coverage

Examining the effectiveness of various leadership styles in Indian companies during the Covid-19 pandemic

The purpose of this study is to find out which leadership styles are effective during the COVID-19 pandemic in India. In this study, the term “effective leadership styles” is used for defining the efficiency level of a leadership style in COVID-19 pandemic. Efficiency level refers to the constructive results which companies could reach due to a specific leadership style. During the pandemic, the main constructive result is the surviving in the market. It has been heavy heartedly witnessed that how dreadful COVID-19 turned out to be. It has affected the whole world. After the great recession that occurred in COVID-19 turned out to be most fatal for whole world economy. It has been seen that difficult for all the businesses to survive. To do so the whole role was of leadership. It was on the leaders whether if they led their company and their followers in right directions or vice versa. It has been seen many well reputed companies have been shedding their costs by downsizing. The proposed study aims to see the role of leadership during this crucial time of COVID-19. Design/methodology/approach — 120 structured questionnaires consisting of 14 statements were distributed to Indian IT companies through online channels such as LinkedIn and WhatsApp. The analysis was performed on the data collected using SPSS. Theoretical Framework — From reviewing the literature about leadership styles, 7 leadership styles have been highlighted as the theoretical basis for our study. The questionnaire has been developed based on the 7 styles. Results – Our study found out that during the pandemic Instruct-style, Transformational, Autocratic, and Strategic leadership styles have high level of effectiveness, and such styles are helping companies to cope with the crisis created by Covid-19 pandemic. Meanwhile our analysis showed that the Transactional, Laissez-Faire, and Democratic styles are not very effective during the crisis. Thus, our study discovered that during the crisis leaders need to take more autocratic role and give very clear instructions to employees. Study provides useful insights for academicians and marketers to device strategies by understanding the factors that portray how leaders can lead their employees in crucial times like COVID-19

Exposure to volatile organic compounds (VOCs) at gas stations: a probabilistic analysis

Gasoline evaporation and spills may cause high air pollution at gas stations. This study aimed to assess exposure to volatile organic compounds (VOCs) at gas stations among customers. Ambient air samples were collected in the fuel dispensing area of 51 gas stations in the Greater Memphis Area, USA, in summer 2017. For the comparison purpose, samples were collected in the ambient air at 20 community sites and in the indoor air of 30 homes, 11 offices, and 15 running vehicles in the same region. Air sampling used Tenax TA thermal desorption (TD) tubes and samples were analyzed by TD-gas chromatography/mass spectrometry (GC/MS) for 70 target compounds. Gasoline-related VOCs were identified using factor analysis, and exposure at gas stations was evaluated using Monte Carlo analysis. Benzene, toluene, ethylbenzene, and xylenes (BTEX) showed the highest concentrations ranging from 2 to 15 μg/m3, ten times higher than those in the community air. Factor analysis confirmed gasoline as the common source of aromatic compounds. VOC concentrations had no association with the number of cars present or environmental parameters. Exposure to aromatic compounds at gas stations represented 2% of the total exposure (i.e., the sum of indoor and outdoor exposures) but 38% of the outdoor exposure among customers. The exposure levels were below the acute health thresholds and presented 0.3 × 10−6 lifetime excess cancer risk. In conclusion, customers’ exposure to VOCs at gas stations has negligible non-cancer and cancer risks. It is also suggested that customers stand away from the nozzle to avoid high personal exposures during refueling

Microbial Diversity of Source and Point-of-Use Water in Rural Haiti – A Pyrosequencing-Based Metagenomic Survey

<div><p>Haiti endures the poorest water and sanitation infrastructure in the Western Hemisphere, where waterborne diseases cause significant morbidity and mortality. Most of these diseases are reported to be caused by waterborne pathogens. In this study, we examined the overall bacterial diversity of selected source and point-of-use water from rural areas in Central Plateau, Haiti using pyrosequencing of 16s rRNA genes. Taxonomic composition of water samples revealed an abundance of Firmicutes phyla, followed by Proteobacteria and Bacteroidetes. A total of 38 bacterial families and 60 genera were identified. The presence of several <i>Klebsiella</i> spp. (tentatively, <i>K</i>. <i>pneumoniae</i>, <i>K</i>. <i>variicola</i> and other <i>Klebsiella</i> spp.) was detected in most water samples. Several other human pathogens such as <i>Aeromonas</i>, <i>Bacillus</i>, <i>Clostridium</i>, and <i>Yersinia</i> constituted significantly higher proportion of bacterial communities in the point-of-use water samples compared to source water. Bacterial genera traditionally associated with biofilm formation, such as <i>Chryseobacterium</i>, <i>Fusobacterium</i>, <i>Prevotella</i>, <i>Pseudomonas</i> were found in the point-of-use waters obtained from water filters or domestic water storage containers. Although the pyrosequencing method utilized in this study did not reveal the viability status of these pathogens, the abundance of genetic footprints of the pathogens in water samples indicate the probable risk of bacterial transmission to humans. Therefore, the importance of appropriate handling, purification, and treatment of the source water needed to be clearly communicated to the communities in rural Haiti to ensure the water is safe for their daily use and intake.</p></div

Rarefaction curves showing observed taxonomic units of bacterial species diversity in the source and point-of-use water samples.

<p>Rarefaction curves showing observed taxonomic units of bacterial species diversity in the source and point-of-use water samples.</p

Genera listed are significantly different between the groups.

<p>Genera listed are significantly different between the groups.</p

Relative abundance of bacterial families residing in source and point-of-use water samples as determined by bTEFAP^®.

<p>Multi-colored stack bar graphs represent the relative abundance of bacterial family in each sample.</p

Dual Hierarchal dendrogram evaluation of the taxonomic classification of source and point-of-use water samples.

<p>Samples are clustered on the X-axis and labeled based upon the water source types. Samples with more similar microbial populations are mathematically clustered closer together. The genera (consortium) are used for clustering. Thus the samples with more similar consortium of bacterial genera cluster closer together with the length of connecting lines (top of heatmap) related to the similarity, shorter lines between two samples indicate closely matched bacterial consortium. The heatmap represents the relative percentages of each bacterial genus. The predominant genera are represented along the right Y-axis. The legend for the heatmap is provided in the upper left corner.</p