During the lockdown phase of the COVID-19 pandemic, equestrian stakeholders faced a dilemma whereby they were required to balance caring for the welfare of horses with adapting to the restrictions imposed to protect public health. The present study investigated the impact of the pandemic on the wellbeing of a sample of industry stakeholders, including horse owners, equine veterinarians, farriers and welfare centre managers (n = 26) using a qualitative methodology. Findings from the interviews indicated that the mental health and wellbeing of veterinarians and horse owners was negatively affected by pandemic-related obstacles to communication and limitations to horse-owner interactions. However, this study also identified several positive outcomes for wellbeing during lockdown resulting from pro-social activities that were engaged with by horse owners to overcome social isolation, the separation of the community and loneliness. These findings provide accounts of ways in which those caring for horses might be challenged during national emergency scenarios, pointing to areas that would benefit from future mental health and wellbeing interventions.
Native ponies are at increased risk of obesity and metabolic perturbations, such as insulin dysregulation (ID), a key risk factor for endocrinopathic laminitis. Management and feeding practices can be adapted to maintain healthy body condition and support metabolic health, but owners may inadvertently provide their ponies with inappropriate management leading to obesity and exacerbating risk of metabolic disease. Adoption of preventative weight management approaches (WMAs), including regular monitoring of body condition, providing appropriate preserved forage, promoting seasonal weight loss, and using exercise accordingly, are key in supporting native ponies' metabolic health. The factors influencing the adoption of WMAs, such as owners' experience and confidence, require exploration. The aim of the current study was to understand factors influencing owners' likelihood to undertake certain WMAs, to develop our understanding of suitable intervention targets. A total of 571 responses to an online cross-sectional questionnaire were analysed. Mediation analysis revealed that whilst long term (≥20 years) experience caring for native ponies was associated with owners increased, self-reported confidence in identifying disease and managing their native ponies, this did not translate to an increased likelihood of implementing WMAs. Conversely, respondents who managed ponies with dietary requirements related to obesity, laminitis, or equine metabolic syndrome were more likely to use WMAs related to feeding, seasonal weight management and exercise. Owner confidence was assessed and rejected as a mediator of the relationship between experience and WMA use. These results highlight the need for further work that elucidates the pathways leading owners to undertake action against obesity without the need for ponies to develop overt disease, as well as suggesting a need for long term managers of native ponies to update management practices with preventative care as the focus.
The equine faecal microbiota is often assessed as a proxy of the microbial community in the distal colon, where the microbiome has been linked to states of health and disease in the horse. However, the microbial community structure may change over time if samples are not adequately preserved. This study stored equine faecal samples from
Abstract Long latency and indolent nature of prostate cancer (PCa) provides a window of opportunity for preventive interventions using natural and synthetic agents. Hence, the focus of this study was to ascertain the chemopreventive role of Quercetin, a bioflavonoid, commonly used to treat prostatitis. Human PCa cells (LNCaP, DU145 and PC3) were treated with different concentrations of Quercetin and its effect on cell survival and apoptosis was determined by MTT assay. Human PCa cells treated with Quercetin showed significant reduction in cell viability and proliferation compared with untreated controls, which was dose and time dependent. In addition to this our FACS analysis showed higher percentage of apoptotic cells after Quercetin treatment compared to untreated cells. Quercetin induced apoptosis in PCa cells is a cumulative effect of modulation of key apoptotic proteins, changes in mitochondrial membrane potential and ROS production. Our results demonstrate that Quercetin is a potent chemopreventive agent, which may improve outcomes of PCa by inhibiting mechanisms involved in tumor progression. Citation Format: Ashley B. Ward, Hina Mir, Neeraj Kapur, Guru Sonpavde, Shailesh Singh. Quercetin inhibits prostate cancer by modulating ROS and key regulators of apoptosis and cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5252. doi:10.1158/1538-7445.AM2017-5252
Abstract Lung cancer is the leading cause of cancer related deaths worldwide in both men and women. Metastasis is responsible for most lung cancer related deaths; therefore, a better understanding of the metastatic processes and therapies designed to prevent the spread of cancer cells are greatly needed. The specific mechanisms that promote metastases have not been fully elucidated. Among all known chemokine receptors involved in cancer progression, most cancer cells including lung cancer express CXCR4. Furthermore, involvement of CXCR4 and CCR7 in breast cancer and CXCR4, CCR9 and CX3CR1 in prostate cancer progression further indicates that multiple chemokine receptors are involved in dictating the multi-step process of metastasis. In this study, we show significantly higher expression of CXCR6 and CXCL16 in lung cancer tissues compared to normal matched tissues. Expression of CXCR6 was significantly higher in adeno- carcinoma compared to squamous cell carcinoma. It addition to these, serum levels of CXCL16, the only natural ligand for CXCR6, was also significantly higher in lung cancer patients compared to normal healthy donor. Furthermore, serum CXCL16 was also significantly higher in patients with adenocarcinoma compared to patients with squamous cell carcinoma. Impact of this chemokines-receptor axis was determined in lung cancer cell lines in vitro, which express CXCR6 and CXCL16. Like tissues, lung cancer cells showed higher expression of CXCR6 and CXCL16 compared to normal lung epithelial cells (NuLi-1). Interestingly, expression of CXCR6 was highest in cell lines derived form adenocarcinoma followed by cell lines from squamous cell carcinoma. Furthermore, we demonstrate that CXCR6 and soluble CXCL16 interaction plays a crucial role in lung cancer cells migration and invasion. The mechanism underlying these clinically and biologically important findings need to be further explored. Increased serum CXCL16 in lung cancer patients with metastatic disease required further validation as a potential therapeutic target and/or diagnostic marker for lung cancer. Citation Format: Hina Mir, Pranav Gupta, Rajesh Singh, Praveen K. Sharma, Gurpreet Kaur, Ashley B. Ward, William E. Grizzle, James W. Lillard, Shailesh Singh. Clinical and biological significance of CXCR6 in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4003. doi:10.1158/1538-7445.AM2014-4003
The COVID-19 pandemic continues to impact human health and welfare on a global level. In March 2020, stringent national restrictions were enforced in the UK to protect public health and slow the spread of the SARS-CoV-2 virus. Restrictions were likely to have resulted in collateral consequences for the health and welfare of horses and ponies, especially those at risk of obesity and laminitis and this issue warranted more detailed exploration. The current study utilised qualitative methodology to investigate the implications of COVID-19 related policies upon equine management and welfare with a focus on horses and ponies at risk of laminitis and obesity. Twenty-four interviews with five sub-groups of key equestrian welfare stakeholders in the UK were conducted between May and July of 2020 to understand the challenges facing equine welfare in the context of laminitis and obesity susceptible animals. Thematic analysis revealed lockdown-associated factors with the potential to compromise welfare of horses and ponies at risk of obesity and laminitis. These included: disparate information and guidance, difficulties enacting public health measures in yard environments, and horses having reduced exercise during the pandemic. Positive examples of clear and consistent information sharing by farriers were reported to have improved horse owner understanding of routine hoof care during lockdown. Analysis suggested that the recommendations for supporting the management-based needs of horses under reduced supervision were not clearly defined, or were not sufficiently disseminated, across the equine industry. These findings support the development of guidelines specific to the care of horses and ponies at risk of obesity and laminitis through collaborative input from veterinary and welfare experts, to reduce the negative impacts of future lockdown events in the UK.
Abstract Prostate cancer (PCa) affects nearly 80% of men worldwide and is the second leading killer after lung cancer. The efficacy of current treatments offered in the clinics is highly compromised due to indolent nature of PCa, which provides large window of opportunity for prevention. Hence, the major focus of this study is to determine the chemo-preventive effects of Quercetin, a bioflavonoid, on prostate cancer. Effect of Quercetin on cell viability and IC50 was determined by MTT assay. The effect of Quercetin on cell motility was determined by wound healing assay. Potential role of Quercetin on cell cycle, apoptosis as well as genes involved in cell motility and invasion was determined using flow cytometry, Real-time qPCR and ELISA. Furthermore, Quercetin induced changes in signaling molecules involved in cell survival/apoptosis, cell cycle and cytoskeletal rearrangement was determined using antibody microarray. Prostate cancer cells treated with Quercetin showed dose and time dependent inhibition of proliferation/viability, and induction of apoptosis as compared to normal prostatic epithelial cells and untreated controls. Prostate cancer cell motility was inhibited in Quercetin treated cells. Prostate cancer cells were arrested in G2 phase of the cell cycle following Quercetin treatment. In addition to these, we found differential expression of caspases, matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs in different PCa cell lines compared to untreated controls. Furthermore, antibody microarray analysis demonstrated selective modulation of genes and associated signaling cascades responsible for apoptosis induction, cellular motility, adhesion and invasion in Quercetin treated cells compared to controls. These findings suggest Quercetin as a potent chemo-preventive agent. In addition to this it can be also used with chemotherapeutic agents directed to G2 phase of the cell cycle, which may improve the efficacy of chemotherapeutics offered in clinics to treat advance prostate cancer. Citation Format: Ashley B. Ward, Pranav Gupta, Gurpreet Kaur, Hina Mir, James W. Lillard, Shailesh Singh. The effects of Quercetin on prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2128. doi:10.1158/1538-7445.AM2014-2128
Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death.Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin.PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death.Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.
Abstract Despite recent advances in treatment and clinical management, prostate cancer is still a leading cause of cancer related deaths among men, primarily because etiopathogenesis of PCa is not well defined. In this regard, chemokines and their corresponding receptors have been shown to play major role in PCa progression, which are often associated with poor therapeutic outcomes. Hence, the focus of this study is to determine the potential role of CXCR6 and its natural ligand CXCL16 in PCa pathogenesis, and potential impact of CXCR6-CXCL16 axis on efficacy of docetaxel, which is currently offered in the clinics as standard care. We investigated expression of CXCR6 and CXCL16 in clinical samples, prostate cancer cell lines and normal prostatic epithelial cells. Expression of CXCR6 and CXCL16 was significantly higher in PCa samples compared to their respective controls, and expression of CXCR6/ CXCL16 was correlated with tumor stage and grades. Similar to patient's samples, expression of CXCR6/CXCL16 was significantly higher in PCa cell lines compared to normal prostatic epithelial cells. Furthermore, levels of phospho -ERK1/2 and -NF-kB, known to be involved in cell growth and survival, were significantly higher in PCa cells treated with CXCL16 compared to untreated controls. In addition to these, role of CXCR6- CXCL16 on genes responsible for cellular adhesion and epithelial-mesenchymal transition were examined. Interestingly, expression of surface E-cadherin and β−catenin following CXCL16 treatment was significantly inhibited compared to untreated cells, suggesting the involvement of CXCR6-CXCL16 interaction in PCa cell migration. Additionally, CXCR6 expressing PCa cells expressed higher α−smooth muscle actin protein, another EMT marker presumably induced by elevated TGF-β, following CXCL16 stimulation. Furthermore, expression of CXCR6, CXCL16 and MMP(s) were elevated in PCa cell following docetaxel treatment in a time and dose dependent manner compared to controls. This may explain the increased efficacy of docetaxel when used in combination with anti-CXCR6 antibody as compared to docetaxel alone. These findings suggest that CXCR6-CXCL16 axis plays a crucial role in pathogenesis of PCa, and inhibition of this axis may have significant impact on disease progression and therapeutics outcomes. Citation Format: Pranav Gupta, Ashley B. Ward, Hina Mir, Gurpreet Kaur, William E. Grizzle, James W. Lillard, Shailesh Singh. Potential role of CXCR6-CXCL16 in prostate cancer progression and chemotherapeutic efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4047. doi:10.1158/1538-7445.AM2014-4047
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