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Fennel constrains growth of pancreatic cancer by inhibition of proliferation and promotion of apoptosis
No full textAbstract
Background: Pancreatic cancer is one of the deadliest cancers. Despite current gold-standard treatment regimens, outcomes are overwhelmingly poor. Novel therapies are necessary to improve treatment of pancreatic cancer. Previous studies show that phytochemicals in fennel decrease the incidence of colon cancer and the multiplicity of breast cancer. However, no studies have explored the effect of fennel on pancreatic cancer. This study investigates the effect of fennel on growth of pancreatic cancer and its possible molecular mechanisms.
Methods: Clonogenic survival assay, cell proliferation, TUNEL staining, and caspase-3 activity kits were used to evaluate the direct effects of fennel seed extract (FE) on cell survival, proliferation, and apoptosis of the widely-studied pancreatic cancer cell line Pan-48. We further investigated possible mechanisms using RT-PCR and IHC.
Results: The percentage of colonies of Pan-48 pancreatic cancer cells decreased significantly after FE treatment. This paralleled a decrease in the OD value of cancer cells treated with FE. Furthermore, the relative caspase-3 activity increased significantly in the presence of FE. The anti-proliferative effect of FE on Pan-48 pancreatic cancer cells correlated with increased expression of p16 and p53. Likewise, the pro-apoptotic effect of FE correlated with increased expression of Fas, TRAIL, TRAILR1 and decreased expression of Bcl-2. Studies about TUNEL and IHC are in progress.
Conclusions: Fennel constrains growth of pancreatic cancer by inhibition of proliferation and promotion of apoptosis. Further investigation may provide insight into the mechanisms of these changes, along with the potential for fennel as a powerful natural agent in treating pancreatic cancer
Saquinavir Increases Phosphorylated Eukaryotic Elongation Factor 2 (peEF2) at the Anal Transition Zone in Transgenic Mice
No full textAbstract
Background: A hallmark of cancer development is eukaryotic elongation factor 2 (eEF2) overexpression. Saquinavir (SQV) has shown to prevent tumorigenesis in an HPV mouse model of anal disease. Our goal was to assess peEF2 expression, as a marker of eEF2 inactivation, in mice with or without topical SQV treatment. We hypothesized that SQV treatment would increase peEF2 expression.
Methods: K14E6/E7 mice with high-grade anal dysplasia that express HPV16 E6/E7 oncoproteins in their epithelium were randomized into treatment groups: no treatment (N = 23), topical 7,12-Dimethylbenz(a)anthracene (DMBA) only (N = 22), topical SQV (2.5%) only (N = 16), and topical SQV with DMBA (N = 10). DMBA use ensured progression of high-grade anal dysplasia to cancer within 20 weeks. At 20 weeks anuses were harvested and Immunofluorescent staining for peEF2 was performed. Tissues were imaged for peEF2 localization at the anal transition (ATZ). Fisher’s exact tests (due to sample size) were performed to analyze peEF2 localization.
Results: 11 of 16 samples in the SQV only group showed localized peEF2 staining at the ATZ; a significant increase compared to control where 6 of 23 samples showed localized staining (p=0.01). 9 of 10 samples in the SQV+DMBA group showed localized staining at the ATZ; a significant increase compared to DMBA only where 11 of 22 samples showed localized staining (p=0.049).
Conclusion: Saquinavir increased staining of peEF2 along squamous epithelium at the ATZ, indicating eEF2 inactivation. Further investigation is required to evaluate if this is required for cancer prevention with SQV
Medicaid Expansion Lowered Uninsurance Rates Among Nonelderly Adults In The Most Heavily Redlined Areas
No full textMedicaid expansion narrowed racial and ethnic disparities in health coverage, but few studies have explored differential impact by exposure to structural racism. We analyzed data on historical residential redlining in US metropolitan areas from the Mapping Inequality project, along with data on uninsurance from the American Community Survey, to test whether Medicaid expansion differentially reduced uninsurance rates among nonelderly adults exposed to historical redlining. Our difference-in-differences analysis compared uninsurance rates in Medicaid expansion and nonexpansion states both before (2009–13) and after (2015–19) the state option to expand Medicaid pursuant to the Affordable Care Act took effect in 2014. We found that Medicaid expansion had the greatest impact on lowering uninsurance rates in census tracts with the highest level of redlining. Within each redline category, there were no significant differences by race and ethnicity. Our results highlight the importance of considering contextual factors, such as structural racism, when evaluating health policies. States that opt not to expand Medicaid delay progress toward health equity in historically redlined communities
Neck pain associated with headaches attributed to rhinosinusitis: an observational study
No full textAbstract
Background/Aim: Neck pain is commonly associated with various headache types, including self-reported sinus headaches. Neck pain’s association with headaches attributed to rhinosinusitis (HAR) diagnosed according to International Classification of Headache Disorders has not been investigated. The aim of this study was to determine if individuals diagnosed with HAR report neck pain and disability.
Methods: This was an observational study. Eighty total participants, including a HAR group and a non-headache group, attended one data collection session. All participants reported whether they get neck pain and completed the Neck Disability Index and Sino-Nasal Outcome Test-22 (SNOT). Additionally, the HAR group completed the Headache Impact Test (HIT-6) and the Visual Analog Scale (VAS). Data analysis included means (SD) for headache duration, HIT-6, and VAS scores in the HAR group. Between group differences were analyzed, with independent t-tests for continuous variables and χ2 for dichotomous variables.
Results: There were significant between group differences for neck pain (p\u3c 0.001) and disability (p\u3c 0.001). In the HAR group 82.5% reported neck pain of moderate disability; 25% of the non-headache group reported neck pain but no associated disability.
Significance/ Conclusion: Neck pain is common in HAR. Patients with HAR perceive neck pain as impacting their quality of life. Clinicians should consider NP as a potential comorbidity when examining and treating people with HAR. Further research is needed to determine potential causes and treatment implications
Exploring variability in stress-induced persistent physical activity: an examination of individual and sex differences
No full textAbstract
A sedentary way of life significantly contributes to chronic and metabolic illnesses, carrying substantial economic implications for healthcare systems worldwide. Although psychological stress exposure is recognized as a risk factor for sedentary lifestyles, there is limited knowledge regarding how stress influences physiology in ways that render individuals more susceptible to chronic inactivity, even long after the stressor has ended. To bridge this knowledge gap, we utilized a rodent model involving voluntary wheel running (VWR) to examine the effects of acute stress on physical activity. In our study, young adult rats subjected to 100 tail-shocks exhibited a prolonged reduction in daily VWR distance for weeks following the stressor, persisting beyond the period of anxiety and depression-like behaviors. Notably, there was a wide range of variation in wheel running distance due to individual differences in stress responses. Additionally, intriguing sex differences were observed, with female rats showing no or a milder detrimental effect on VWR following the same stressor. Depending on the types of running wheels, the stress even led to an enhancement of VWR activity, particularly among low-running females, suggesting a potential protective role of estrogen against stress-induced physical inactivity. To further delve into these findings, we are currently investigating estrogen and estrogen receptor-dependent molecular processes in brain regions linked to exercise motivation and execution. Understanding the physiological mechanisms underlying individual and sex differences is essential not only for comprehending the lasting impacts of acute stress on physical activity but also for identifying innovative interventions to combat sedentary lifestyles
Wild Jujube suppresses growth of bronchial epithelial cells and upregulates PDL1 and OX40L
No full textAbstract
Background: Lung cancer is the leading death-causing cancer in the US. Wild Jujube (WJ) is a popular fruit in Asia and has been shown to have anti-cancer properties including lung cancer. However, little is known about its effects on normal bronchial epithelial cells. Co-stimulatory molecules such as PDL1, PDL2, 4-1BBL, OX40L, and CD74 are a group of cell-surface molecules activating or inhibiting T cells. These molecules play a critical role in T-cell activation against cancer. However, the role of WJ on the expression of the co-stimulatory molecules is unknown yet. This study will investigate the effects of WJ on growth in bronchial epithelial cells and on the expression of key co-stimulatory molecules.
Methods: Normal bronchial epithelial cell line, B2B, was treated with WJ extract (WJE). Clonogenic Survival Assay and Cell Proliferation kit were utilized to measure the growth of B2B in the presence of WJE. RT-PCR and IHC were utilized to determine the effects of WJE extract on expression of key co-stimulatory molecules PDL1, PDL2, 4-1BBL, OX40L, and CD74.
Results: The percentage of colonies of B2B cells was significantly lower in the presence of WJE. In line with this, a decrease in the OD value of B2B cells in the presence of WJE was also found. PDL1, PDL2, 4-1BBL, OX40L and CD74 were constitutively expressed in B2B cells. The mRNA expression levels of PDL2, 4-1BBL, and CD74 were comparable in the presence of WJE to those in the absence of WJE. However, the mRNA expression levels of PDL1 and OX40L were much higher in the presence of WJE. IHC for PDL1 and OX40L is in progress.
Conclusion: WJ suppresses the growth of bronchial epithelial cells and upregulates the expression of PDL1 and OX40L. The clinical significance of the upregulation of OX40L is unclear. However, the upregulation of PDL1 by WJ may protect normal bronchial epithelial cells from immune attack while lung cancer cells are targeted by immunity. Such a study may provide useful information to design WJ as an option for the treatment of lung cancer
Incidence of floating toe with Weil osteotomy: A systematic review
No full textAbstract
Purpose: This systematic review and meta-analysis aimed to reevaluate the current incidence of the floating toe complication following Weil osteotomy and possible reasons for a change.
Introduction: Floating toe subsequent to a Weil osteotomy is a well-known complication11. Current Weil osteotomy floating toe incidence is unknown as is the associated complication rate variability with adjunctive procedures. The purpose of this study aims to reevaluate the current incidence of floating toe complications following a Weil osteotomy, compared to the previously reported rate of 36% by Highlander et al in 2011.
Methodology: Following PRISMA guidelines, a systematic review was conducted from 2012 on using PubMed, SCOPUS, and Cochrane Library utilizing specific keywords. Inclusion criteria encompassed individuals aged 18 or older, excluding certain conditions and prior surgeries. This yielded 2258 articles, refined to 782 unique ones for meticulous analysis. Thirteen pertinent articles were selected for in-depth examination, with nine preceding to full analysis including Weil osteotomy floating toe incidence, adjunctive procedures, weight-bearing status.
Results: Demographics, complication frequencies, and Weil osteotomy data were analyzed from 1018 cases. Most studies were clinical evidence level 3 (n=4), followed by level 2 (n=3), and our lowest being level 4 (n=2). A total of 741 osteotomies were included with predominantly female participants and an average age of 58.8. Floating toe incidence post-osteotomy was 20%.
Conclusion: A significant decrease in floating toe incidence post-Weil osteotomies was observed compared to the benchmark study in 2011
Lunch Break
No full textAttendees get a break for lunch with an option to pick up a free lunch in the hallway outside rooms E4117 and E4119
Oncogenes MYC, MAX, and MNT upregulate branched chain amino acid metabolism in peripheral T cell lymphoma
No full textAbstract
Peripheral T cell lymphoma (PTCL) is an aggressive non-Hodgkin lymphoma arising in T lymphocytes. Overexpression of the oncogenes MYC, MAX, and MNT is implicated in non-Hodgkin lymphomas where these genes control growth and proliferation by regulating the expression of metabolic genes. The mitochondrial branched-chain aminotransferase (BCAT2) and ketoacid dehydrogenase (BCKDHA, and DBT) genes encode for enzymes that breakdown branched-chain amino acids (BCAAs). BCAAs are a source of energy and metabolites for lymphoma cells. We aimed to investigate whether the expression of MYC, MAX and MNT correlate with that of BCAT2, BCKDHA, and DBT and to understand whether overexpression of BCAT2, BCKDHA and DBT in PTCL patients correlates with lower cancer survival.
The genomics analysis and visualization platform (R2) was used to access information about the overall survival and gene expression of 193 specimens from newly diagnosed PTCL patients. Kaplan Meier survival curves were downloaded from the platform along with the 2log expression values of each gene of interest. Pearson’s correlation coefficient (R) was used to measure the strength and direction of the relationship between the oncogenes and the metabolic genes.
Results indicated a positive and statistically significant correlation between BCAT2 and MYC, BCKDHA and MYC/MAX, and DBT and MAX/MNT. Overexpression of BCAT2, BCKDHA, and DBT correlated with significantly lower PTCL survival. The findings suggested that the oncogenes upregulate the BCAA metabolic genes in PTCL. While the molecular mechanism of these correlations needs to be addressed experimentally, the findings may serve as a basis for future pharmacotherapy for PTCL patients
A description of the hindlimb of Miracinonyx trumani with implications for its ecological niche
No full textAbstract
Miracinonyx trumani was a species of felid that lived during the late Pleistocene across North America. It has been called the ‘American Cheetah’ due to its morphological similarities with the African cheetah Acinonyx jubatus, and because of those similarities it has been thought to be primarily a cursorial animal. Previous studies of M. trumani have described the cranium and the forelimb or have described the skeleton of juveniles; no studies have yet described the hindlimb in adults. We completed this study to better understand the ecological role of the American cheetah in the Pleistocene ecosystem.
We analyzed the hindlimb of M. trumani, Puma concolor, and Acinonyx jubatus using 3D models made from CT scans. Our results indicate M. trumani hindlimbs have several adaptations for a cursorial lifestyle that it shares with the African cheetah. These include an innominate with a well-defined ischial tuberosity, a curved tibia, and a pronounced neck of the femur. It also has some traits that more closely resemble the scansorial Puma, including the distal articular surface of the femur with a matching tibial plateau, however, some of these characters were modified secondarily for speed, such as an enlarged tibial crest as in the cheetah, which would increase the lever arm of the quads. Additional characters not optimal for cursoriality include a shallower malleolar mortise with less well-defined articular surfaces for the trochlea of the astragalus. This mix of traits means that M. trumani was more adapted to a cursorial lifestyle than its sister species Puma concolor, but was not likely to be as cursorial as the A. jubatus