Teaching STEM subjects through project-based learning (PBL) in a global classroom offers a transformative educational experience that equips students with both technical skills and global competencies. This paper explores the integration of PBL in Biomedical Science education across diverse, international settings, highlighting its impact on student engagement, cross-cultural understanding, and collaborative problem-solving. By connecting students from different regions through virtual platforms, a global classroom provides opportunities to work on real-world projects that address global challenges, such as, access to healthcare, public health, etc. This paper presents our work-in-progress global classroom programme, developed in collaboration with an Indian higher education institution and grounded in the project-based learning (PBL) teaching model. It explores the tools that facilitate effective PBL in a global context, alongside potential challenges and strategies for successful implementation. The proposed model, which is adaptable to other STEM disciplines, highlights the importance of incorporating a global perspective into STEM education, equipping students with the skills and knowledge needed to navigate and contribute to an increasingly interconnected world.
The numerous side effects and adverse health implications associated with chemotherapies have long plagued the field of cancer care. Whilst in some cases a curative measure, this highly toxic intervention consistently scores poorly on quantitative measures of tolerability and safety. Of these side effects, cardiac and microvascular defects pose the greatest health risk and are the leading cause of death amongst cancer survivors who do not succumb to relapse. In fact, in many low-grade cancers, the risk of recurrence is far outweighed by the cardiovascular risk of morbidity. As such, there is a pressing need to improve outcomes within these populations. Polyphenols are a group of naturally occurring metabolites that have shown potential vasoprotective effects. Studies suggest they possess antioxidant and anti-inflammatory activities, in addition to directly modulating vascular signalling pathways and gene expression. Leveraging these properties may help counteract the vascular toxicity induced by chemotherapy. In this review, we outline the main mechanisms by which the endothelium is damaged by chemotherapeutic agents and discuss the ability of polyphenols to counteract such side effects. We suggest future considerations that may help overcome some of the published limitations of these compounds that have stalled their clinical success. Finally, we briefly explore their pharmacological properties and how novel approaches could enhance their efficacy while minimising treatment-related side effects.
Endothelin-1 (ET-1) plays a physiological role as a potent vasoconstrictor. It is implicated in an array of diseases, and its signalling is often found to be overactivated within cancers. ET-1 has been found to potentiate hallmarks of cancer progression such as cell proliferation, invasion and metastasis, as well as angiogenesis. ET-1 has also been implicated in inducing the epithelial–mesenchymal transition (EMT) and promoting resistance to anticancer drugs. Many preclinical efforts have been made to target ET-1 expression within cancer, such as by using ET-1 receptor antagonists, many of which have been approved for treating pulmonary hypertension. Targeting ET-1 has been shown to improve the response to various other cancer therapeutics, highlighting the potential benefits targeting this peptide may exert. Drug repurposing is an attractive strategy, and exploration of this avenue may be promising for targeting ET-1 in cancer. There are many clinical trials which have been completed and are currently undergoing involving the repurposing of ET-1 receptor antagonists for cancer treatment. In this review, the pathways through which ET-1 potentiates cancer will be discussed, as well as where the opportunity for therapeutic intervention lies in relation to cancer.
Background: We present a new original method of modeling an intra-articular fracture of the long tubular bone in laboratory animals.Objective: To create a new experimental model of an intra-articular fracture of the long tubular bone and to approve it for comprehensive evaluation of morphofunctional parameters of cartilage and bone healing.Materials and methods: The experiment was performed on 30 white sexually mature Wistar rats. Modeling involved layer-by-layer dissection of tissues along the anteromedial surface and formation of an incomplete fracture of the femoral medial condyle using a sharp L-shaped working end of an 0.2 × 0.2 сm instrument perpendicular to the medial condyle with a slight single muscle force. The rats were euthanized in groups of 10 animals on days 7, 14, and 30. We performed knee radiography and determined blood osteocalcin and BMP-7 levels. The Mankin score was used in the histological evaluation of the articular cartilage changes. The groups were compared using the Kruskal-Wallis test. P < .05 was considered statistically significant.Results: We noted statistically significant differences (P < .0001) when comparing the groups using the Mankin score. The post hoc test revealed statistically significant differences in the Mankin scores between days 7 and 14 (P = .014) and between days 7 and 30 (P < .0001). Group comparisons showed no statistically significant differences in blood osteocalcin levels (P = .518). However, there were statistically significant differences (P = .0028) between the groups in blood BMP-7 levels. The post hoc test revealed statistically significant differences in blood BMP-7 levels between days 7 and 14 (P = .048) and between days 14 and 30 (P = .0195).Conclusions: The developed experimental model of intra-articular fractures of long tubular bones allows for a comprehensive assessment of reparative processes of cartilage and bone tissue. The model is close to the real mechanism of pathology development.
Heterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved in endometrial cancer have yet to be elucidated. We aimed to explore the potential mechanisms of heterogeneous CAFs in promoting endometrial cancer progression. The presence of melanoma cell adhesion molecule (MCAM; CD146) positive CAFs was confirmed by tissue multi-immunofluorescence (mIF), and fluorescence activated cell sorting (FACS). The biological functions were determined by wound healing assays, tuber formation assays and cord formation assays. The effects of CD146 + CAFs on endometrial cancer cells were studied in vitro and in vivo. The expression level of interleukin 10 (IL-10) was measured by quantitative real time polymerase chain reaction (qRT-PCR), western boltting and enzyme linked immunosorbent assays (ELISAs). In addition, the transcription factor STAT3 was identified by bioinformatics methods and chromatin immunoprecipitation (ChIP). A subtype of CAFs marked with CD146 was found in endometrial cancer and correlated with poor prognosis. CD146 + CAFs promoted angiogenesis and vasculogenic mimicry (VM) in vitro. A xenograft tumour model also showed that CD146 + CAFs can facilitate tumour progression. The expression of IL-10 was elevated in CD146 + CAFs. IL-10 promoted epithelial-endothelial transformation (EET) and further VM formation in endometrial cancer cells via the janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signalling pathway. This process could be blocked by the JAK1/STAT3 inhibitor niclosamide. Mechanically, STAT3 can bind to the promoter of cadherin5 (CDH5) to promote its transcription which may be stimulated by IL-10. We concluded that CD146 + CAFs could promote angiogenesis and VM formation via the IL-10/JAK1/STAT3 signalling pathway. These findings may lead to the identification of potential targets for antiangiogenic therapeutic strategies for endometrial cancers.
Gut microbiome alterations are associated with various cancers including brain tumours such as glioma and glioblastoma. The gut communicates with the brain via a bidirectional pathway known as the gut-brain axis (GBA) which is essential for maintaining homeostasis. The gut microbiota produces many metabolites including short chain fatty acids (SCFAs) and essential amino acids such as glutamate, glutamine, arginine and tryptophan. Through the modulation of these metabolites the gut microbiome is able to regulate several functions of brain cells, immune cells and tumour cells including DNA methylation, mitochondrial function, the aryl hydrocarbon receptor (AhR), T-cell proliferation, autophagy and even apoptosis. Here, we summarise current findings on gut microbiome with respect to brain cancers, an area of research that is widely overlooked. Several studies investigated the relationship between gut microbiota and brain tumours. However, it remains unclear whether the gut microbiome variation is a cause or product of cancer. Subsequently, a biomarker panel was constructed for use as a predictive, prognostic and diagnostic tool with respect to multiple cancers including glioma and glioblastoma multiforme (GBM). This review further presents the intratumoural microbiome, a fascinating microenvironment within the tumour as a possible treatment target that can be manipulated to maximise effectiveness of treatment via personalised therapy. Studies utilising the microbiome as a biomarker and therapeutic strategy are necessary to accurately assess the effectiveness of the gut microbiome as a clinical tool with respect to brain cancers.
The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (p < 0.0001) in cases with unfavourable prognosis. Univariate survival analysis highlighted the significant role of these factors in progression-free survival, while multivariate Cox analysis identified VM and CD146+ vessels as predictive factors. This study demonstrates, for the first time, that VM, CD146, and CD105-positive vessels are involved in EA prognosis, suggesting their potential as independent prognostic indicators and targets for antiangiogenic therapy. However, these findings require further validation through large-scale studies.
Project-based learning (PBL) has been found to deepen learning and develop employability skills for students through active engagement with the learning materials. Foundation, first and second year Biomedical Science students at the University of Sussex were introduced to a PBL exercise. Each class had an approximate student to staff ratio of eighty to two. Students were put into groups of four to five and asked to create a revision guide for a disease system, which was then shared among the cohort for exam preparation. Students were later surveyed on the effectiveness of this group activity. 74% indicated the activity helped them integrate knowledge from previous modules, with the majority of the students scoring the activity 4 out of 5 for consolidation of knowledge. 75% of the participants who took part before the pandemic indicated that the tasks enabled them to build a cohort identity, with 59% students feeling similarly during the pandemic. Additionally, we qualitatively assessed the development of transferrable skills, such as teamwork, effective communication and time management. The results of the questionnaire suggested that students were able to gain these skills. This paper outlines the study, discusses benefits and limitations, and provides potential solutions for the future.
Project-based learning (PBL) is a widely used active learning approach in science, technology, engineering and mathematics (STEM) education, but concerns about unequal participation in group work can arise. To address this, we incorporated peer evaluation via the Buddycheck tool into a summative PBL assessment. In this study, students worked in small groups to create and present posters, with Buddycheck enabling them to evaluate each other’s contributions. This peer evaluation process generated an adjustment factor, which was applied to the final group mark to assign individual grades based on performance. Students reported that the peer evaluation promoted fairness in grading and increased their accountability, leading to higher engagement in group activities. They also found the exercise valuable for consolidating their knowledge and improving communication skills. Overall, the use of Buddycheck in PBL was well received, with students expressing greater satisfaction and a sense of equity in the grading process. The tool not only improved learning outcomes but also contributed to better group dynamics and an overall improvement in final grades.
Decolonising the curriculum (DtC) is an emerging concept that continues to challenge higher education institutions globally, with educators and scholars increasingly recognising how traditional curricular structures, content, and pedagogical practices can reinforce colonial biases and marginalise certain student groups. DtC can be seen as a process rather than a phenomenon, one which is ongoing and multiplexed, consisting of elements that aim to dismantle the hierarchy between staff and students and question the ways in which knowledge is produced, valued, and disseminated. The expected outcome is to provide students with an education which is equitable, inclusive, and relevant to their personal lives and experiences. Efforts in DtC have continued to gain traction, but assessment practices remain overlooked as a crucial component, with most decolonising efforts focussed towards content and pedagogy. As such, this review aims to contribute to the conversation by exploring the roots and impacts of colonisation on higher education, particularly within the context of assessment in STEM subjects. We examine various elements of decolonised assessment methods and ultimately suggest project-based learning (PBL) as a comprehensive approach that brings together the aforementioned decolonial elements, illustrating this concept through the examination of a PBL assessment mode study conducted at the University of Sussex.
CD109 antigen on the endothelial cell surface plays an important role in vascular pathology. The aim of the work was to investigate the effect of the immobilization of CD109 antigen with specific antibodies on nanomechanical properties of human umbilical endothelial cells (HUVECs) using atomic force microscopy in quantitative nanomechanical property mapping mode (PeakForce QNM). Anti-CD109 antibodies induced significant stiffening of the cell surface Me(LQ; UQ): in 1.45(1.07;2.29) times with respect to control cells for fixed cells and in 4.9(3.6;5.9) times with respect to control cells for living cells, and changes in the spatial distribution of cell surface mechanical properties. The changes in the HUVEC's mechanical properties were accompanied by the activation of the TGF-/Smad2/3 signaling pathway and reorganization of the vimentin and actin cytoskeletal elements. Our findings show that blocking CD109 antigen using anti-CD109 antibodies leads in HUVECs to the processes similar to that occur after cell TGF-β-signaling activation. Therefore, we suggest that CD109 antigen may be involved in regulating the mechanical behavior of endothelial cells.
COVID-19 has brought to light the systemic racism faced by ethnic minorities in the UK. During the pandemic, we saw an increase in anti-Asian hate crimes and a lack of support from the government given to both patients and healthcare workers from minority backgrounds on the front lines. This lack of support potentially contributed to the increased susceptibility of ethnic minorities to COVID-19 and also their hesitancy toward the vaccine, particularly the south Asian communities. In this paper we discuss potential reasons for COVID-19 vaccine hesitancy among south Asian groups. Additionally, we propose that introducing a decolonised curriculum in secondary school may enhance cultural awareness with historical context among the white British populations, allowing for more inclusion for south Asian communities. By exploring ways to decolonise specific subjects in the secondary curriculum, this paper aims to set out a guideline for teachers and education professionals on expanding secondary school pupils’ knowledge of racial issues and equality, to start the process of educating a new generation appropriately. We propose that decolonising the secondary school curriculum is a potential long-term solution to eradicating racism and discrimination.
Current cardiac biomarkers, troponins and brain natriuretic peptide, are primarily used to assist in the diagnosis or exclusion of myocardial damage and congestive heart failure, respectively. The use of these biomarkers in chemotherapy-induced cardiotoxicity has been evaluated by various studies. However, neither biomarker provides early predictive value, leaving many cancer survivors with irreversible cardiac injury. Assessing endothelial dysfunction could be an effective measure of chemotherapy-induced cardiotoxicity at the vascular level. Risk profiling and detection of vascular toxicities may offer predictive biomarkers to prevent chronic manifestation of irreversible cardiotoxicities. Emerging interest has developed in finding biomarkers that could ideally provide earlier prognostic value. Thus, the aim of this review is to give an overview of current blood-based cardiac biomarkers and discuss the potential of endothelin-1 (ET-1) and more stable peptide fragments of ET-1 synthesis as biomarkers of endothelial dysfunction. For instance, endothelin-like domain peptide (ELDP) and C-terminal pro-endothelin-1 (CT-proET-1) demonstrated high-sensitivity and longer clearance rate than ET-1. Thus, investigating their biomarker role in chemotherapy-induced cardiotoxicity is important and could provide additional insights for identifying patients at risk. Also, additional research is required to fully understand ELDP-mediated vasoconstriction. This review will discuss the future development of ET-1, ELDP and CT-proET-1 as prospective predictive biomarkers.
Cancer remains a formidable global health challenge, and as such, investigators are constantly exploring un- derlying mechanisms that drive its progression. One area of interest is the role of lysosomal enzymes, such as cathepsins, in regulating cancer growth and development in the tumour microenvironment (TME). Pericytes, a key component of vasculature, play a key role in regulating blood vessel formation in the TME, have been shown to be influenced by cathepsins and their activity. Although cathepsins such as cathepsins D and L have been shown to induce angiogenesis, currently no direct link is known between pericytes and cathepsins interaction. This review aims to shed light on the potential interplay between pericytes and cathepsins in the TME, high- lighting the possible implications for cancer therapy and future research directions.
ImportanceTo our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.ObjectiveTo study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.Design, Setting, and ParticipantsThis was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.Main Outcomes and MeasuresFor analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.ResultsOf the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.Conclusions and RelevanceThis cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.