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Ischemic heart disease, a major risk factor for myocardial infarction (MI), occurs when the blood vessels supplying oxygen-rich blood to the heart become partially or fully occluded by lipid-rich plaques, resulting in myocardial cell death, remodeling, and scarring. In addition, MI occurs as result of lipid-rich plaque rupture, resulting in thrombosis and vessel occlusion. Cardiac fibroblasts (CFs) and CF-derived growth factors are crucial post-MI in myocardial remodeling. Information regarding the regenerative phenotypes of CFs is scarce; however, regenerative CFs are translationally relevant in myocardial regeneration following MI. The emerging technologies in regenerative cardiology offer cutting-edge translational opportunities, including synthetic cells. In this review, we critically reviewed the current knowledge and the ongoing research efforts on application of synthetic cells for improving cardiac regeneration post-MI. Impact statement Synthetic cells offer tremendous regenerative potential in otherwise deleterious cardiac remodeling postmyocardial infarction. Understanding the role of fibroblasts in cardiac healing and the therapeutic applications of synthetic cells would open a multitude of novel cardiac regenerative approaches. The novel concept of synthetic fibroblasts that emulate native cardiac fibroblasts can provide an effective solution in cardiac healing.

BACKGROUND: Oropharyngeal myofunctional therapy is a multi-component therapy effective to reduce the severity of obstructive sleep apnoea (OSA). However, existing protocols are difficult to replicate in the clinical setting. There is a need to isolate the specific effectiveness of each component of the therapy. OBJECTIVE: To assess the effects of a 6 weeks tongue elevation training programme in patients with OSA. METHODS: We conducted a multicentre randomised controlled trial. Eligible participants were adults diagnosed with moderate OSA who presented low adherence to continuous positive airway pressure therapy (mean use

The global burden of cerebrovascular disease, especially cerebral infarction has been increasing at an alarming rate with the atherosclerosis in carotid arteries as the primary risk factor. Despite the active involvement of minimally oxidized LDL (oxLDL) in atherosclerosis, limited information is available regarding the role of oxLDL in the pathogenesis of cerebrovascular diseases. The present study utilized the carotid bifurcation tissues and isolated carotid SMCs challenged with oxLDL from clinically relevant minimally invasive minimally-oxLDL-induced carotid atheroma microswine model to examine the levels of pro-atherogenic and pro-inflammatory mediators and cellular processes following immunostaining approaches. The immunopositivity of IL18, PDGFRA, IL17, LOX1, TLR4, MYF5, IL1B, and PDPN were increased in the carotid artery bifurcation tissues with a concomitant decrease in DAMPs, HMGB1 and S100B in oxLDL (600μg)-treated group compared to non-intervention control. Moreover, the cultured SMCs displayed increased level of IL18, LOX1, TLR4, MYF5, NLRP3, and PDPN upon challenging with oxLDL (100 mg/ml) compared to non-treatment control. In addition, the SMCs treated with oxLDL were resistant to the peroxidation of lipids as evident from lipid peroxidation staining. Also, the oxLDL displayed compromised mitochondrial membrane potential based on mitochondrial pore transition assay and increased hypertrophy due to decreased level of microtubules. Overall, oxLDL alters the expression status of pathological mediators and multiple biological processes in carotid SMCs aggravating carotid atherosclerosis. The understanding regarding the molecular mechanisms underlying oxLDL-driven pathological events would open novel translational avenues in the management of carotid atherosclerosis.

Cardiovascular disease (CVD) is a major contributor to annual deaths globally. Atherosclerosis is a prominent risk factor for CVD. Although significant developments have been recently made in the prevention and treatment, the molecular pathology of atherosclerosis remains unknown. Interestingly, the recent discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) introduced a new avenue to explore the molecular pathogenesis and novel management strategies for atherosclerosis. Initial research focussed on the PCSK9-mediated degradation of low density lipoprotein receptor (LDLR) and subsequent activation of pro-inflammatory pathways by oxidised low density lipoprotein (ox-LDL). Recently, PCSK9 and lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) were shown to positively amplify each other pro-inflammatory activity and gene expression in endothelial cells, macrophages and vascular smooth muscle cells. In this literature review, we provide insight into the reciprocal relationship between PCSK9 and LOX-1 in the pathogenesis of atheroma formation and plaque instability in atherosclerosis. Further understanding of the LOX-1-PCSK9 axis possesses tremendous translational potential to design novel management approaches for atherosclerosis.

Currently, the most effective mosquito repellents employ the use of the chemical N, N-Diethyl-meta-toluamide (DEET), often considered the gold standard of repellents. However, as DEET continues to be widely used, it is beginning to lose efficacy as mosquitoes gradually gain resistance to it. Additionally, DEET only protects the skin that it is applied on, and therefore, it is difficult to achieve 100% repellency for the entire body. As urbanization and climate change continue to increase the threat of widespread mosquito-borne illnesses, new forms of repellents must be developed to combat the possibility of an epidemic. Previous studies indicate that a multitude of insects, including spiders, flies, and mosquitoes, avoid electrostatic fields at sufficiently high voltages. In this study, I evaluate if electrostatic fields can be used as a potential personal repellent against mosquitoes and an alternative to chemical sprays. I found that by charging the surface of a person’s body with a high voltage (9800V) but minuscule current, I created a safe and effective method that repels mosquitoes from landing on the skin. This method has similar efficacy to DEET, with near 100% repellency after 20 minutes of charging. It also has the advantage of not needing to be reapplied and provides full-body protection, allowing greater protection to the user than DEET. These results introduce a promising method of repelling mosquitoes, that used together with present-day chemical repellents, can help provide greater protection to malaria-endemic countries.

Emphysematous cystitis (EC) is a rare, severe, urinary tract infection caused by gas-producing bacteria. It is characterized by the accumulation of air inside the bladder wall and/or lumen and is common among elderly diabetic females. This case of a 90-year-old female, who underwent bilateral iliac angioplasty and stenting, is the first published correlation between iliac angioplasty and the development of EC. The endovascular procedure performed was a success, but later on, she was confused and developed frank haematuria with a fall in haemoglobin levels. CT revealed severe EC with abundant gas tracking outside of urinary bladder into the extraperitoneal space. She was catheterized and empirical antibiotics were started and converted based on the culture sensitivities. Frequent follow-up ensured the resolution of a conservatively managed case. It is essential to increase the awareness of EC associated with angioplasties among the healthcare staff, particularly those undertaking vascular procedures.

This article looks at the strategies religious non-governmental organizations (RNGOs) with strong transnational linkages use to maintain a continued presence in mainland China. It does so by utilizing neo-institutional theory as an instrument for analysis, with an emphasis on outlining the coercive, mimetic, and normative pressures RNGOs face. One of the key findings of the study is that there is creative circumvention of isomorphic pressures by working with local agents, fostering trust with the local government, and keeping a low profile. Moreover, RNGOs dealt with the uncertain institutional environment in China through staff exchanges, denominational supervision, tapping into global platforms, and undergoing a professionalization process.

This article questions the extent future generations of immigrants will engage with practices of religious transnationalism through its ethnic institutions. I examine how leaders of the next generation of English-speaking Chinese-Canadian evangelicals made sense of their participation in the Chinese Coordination Centre of World Evangelism, a movement that rallies behind both pan-Chinese and Chinese elect identities. I argue that the call to religious mobilization grounded on Chinese ethnicity stands on tenuous grounds and propose linguistic, geographical, generational, and ideological fractures as mechanisms on how the Chinese diaspora’s future generations’ participation in ethnically based transnational religious organizations may diminish. I conclude that these developments would push ‘negotiated transnational religious networks’ into a state of ‘renegotiation.’

DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.

Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild‐caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species’ lifespan.

We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and obesity. We demonstrated that chow-fed Ldlr-/-xLcat+/+ mice have elevated hepatic endoplasmic reticulum (ER) stress, which promotes IR, compared with wild-type controls, and this effect is normalized in Ldlr-/-xLcat-/- mice. In the present study, we tested the hypothesis that hepatic ER cholesterol metabolism differentially regulates ER stress using these models. We observed that the Ldlr-/-xLcat+/+ mice accumulate excess hepatic total and ER cholesterol primarily attributed to increased reuptake of biliary cholesterol as we observed reduced biliary cholesterol in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced. Expression of these genes was reversed in the Ldlr-/-xLcat-/- mice, accounting for the normalization of total and ER cholesterol and ER stress. Upon feeding a 2% high cholesterol diet (HCD), Ldlr-/-xLcat-/- mice accumulated a similar amount of total hepatic cholesterol compared with the Ldlr-/-xLcat+/+ mice, but the hepatic ER cholesterol levels remained low in conjunction with being protected from HCD-induced ER stress and IR. Hepatic ER stress correlates strongly with hepatic ER free cholesterol but poorly with hepatic tissue free cholesterol. The unexpectedly low ER cholesterol seen in HCD-fed Ldlr-/-xLcat-/- mice was attributable to a coordinated marked up-regulation of ACAT2 and suppressed SREBP2 processing. Thus, factors influencing the accumulation of ER cholesterol may be important for the development of hepatic insulin resistance.

The authors hypothesized that published hypertension rates in Tanzania were influenced by the physiological response of individuals to blood pressure (BP) testing, known as the white-coat effect (WCE). To test this, a representative sample of 79 participants from a baseline cohort of 2322 people aged 70 years and older were followed to assess BP using conventional BP measurement (CBPM) and ambulatory BP monitoring (ABPM). There was a significant difference between daytime ABPM and CBPM for both systolic BP (mean difference 29.7 mm Hg) and diastolic BP (mean difference 7.4 mm Hg). Rates of hypertension were significantly lower when measured by 24-hour ABPM (55.7%) than by CBPM (78.4%). The WCE was observed in 54 participants (68.4%). The WCE was responsible for an increase in recorded BP. Accurate identification of individuals in need of antihypertensive medication is important if resources are to be used efficiently, especially in resource-poor settings.

This study uses self-determination theory to explore the mechanisms of filial piety in the academic motivation of eight high-achieving secondary school seniors at an international school in South Korea, resulting in several findings. First, the students attributed their parents’ values and expectations as a major source of the students’ understanding of filial piety responsibilities in their academic pursuit. Second, the participants found ways to justify the authoritative parenting they received through a reciprocal relationship, especially when their parents were autonomy-supportive. Third, the definitions of filial piety responsibilities varied, depending on the students’ personal and familial idiosyncrasies.

The innate immune responses of early vertebrates, such as bony fishes, play a central role in host defence against infectious diseases and one of the most important effector cells of innate immunity are macrophages. In order for macrophages to be effective in host defence they must be present at all times in the tissues of their host and importantly, the host must be capable of rapidly increasing macrophage numbers during times of need. Hematopoiesis is a process of formation and development of mature blood cells, including macrophages. Hematopoiesis is controlled by soluble factors known as cytokines, that influence changes in transcription factors within the target cells, resulting in cell fate changes and the final development of specific effector cells. The processes involved in macrophage development have been largely derived from mammalian model organisms. However, recent advancements have been made in the understanding of macrophage development in bony fish, a group of organisms that rely heavily on their innate immune defences. Our understanding of the growth factors involved in teleost macrophage development, as well as the receptors and regulatory mechanisms in place to control them has increased substantially. Furthermore, model organisms such as the zebrafish have emerged as important instruments in furthering our understanding of the transcriptional control of cell development in fish as well as in mammals. This review highlights the recent advancements in our understanding of teleost macrophage development. We focused on the growth factors identified to be important in the regulation of macrophage development from a progenitor cell into a functional macrophage and discuss the important transcription factors that have been identified to function in teleost hematopoiesis. We also describe the findings of in vivo studies that have reinforced observations made in vitro and have greatly improved the relevance and importance of using teleost fish as model organisms for studying developmental processes.