Search Results (9)

Enterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this study, we successfully infected mice of different ages using a mouse-adapted EV71 strain, resulting in disease and mortality. We compared immune system responses between infected and uninfected mice of different ages to identify key pathogenic targets during EV71 infection. Our findings revealed that the level of Group 3 Innate Lymphoid Cells (ILC3s) in mice negatively correlated with the severity of disease induced by EV71 infection. We conducted anti-ILC3 cytokine injections and cytokine neutralizing antibody experiments on 14-day-old EV71-infected mice. The results showed that the cytokine IL-17 secreted by ILC3 cells had a mild protective effect, while IL-22 promoted inflammatory responses. Our research demonstrates that ILC3 cells play a dual role in EV71 infection. These findings not only clarify key immune factors in the progression of EV71-induced disease but also provide a promising approach for the early diagnosis and treatment of severe EV71 infections. Full article

Background: Understanding the causal relations between dietary habits and stroke is crucial for prioritizing public health interventions and developing effective health strategies. This study utilized Mendelian randomization (MR) analysis to examine the causal associations between 20 dietary habits and various stroke subtypes, aiming to identify potential mediators and evaluate the proportions of mediation. Methods: A two-sample MR analysis was conducted to examine the causal relationships between dietary habits and stroke incidence. Mediation analysis, two-step MR (TSMR), and multivariable MR (MVMR) were employed to identify potential mediators. Genetic data pertaining to dietary habits and stroke were obtained from extensive genome-wide association study (GWAS) consortia. The inverse variance-weighted (IVW) method served as the primary analytical approach, with the additional scrutiny of significant correlations conducted through the Egger regression, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and weighted median techniques. Results: Our analyses indicated that genetically predicted intakes of dried fruits, cheese, cereal, oily fish, and hot drink temperatures were protective against stroke, whereas higher intakes of lamb/mutton, poultry, and added salt significantly elevated stroke risk. Specifically, dried fruit consumption demonstrated a protective effect against total stroke (β = −0.009, p = 0.013), ischemic stroke (β = −0.475, p = 0.003), and small-vessel ischemic stroke (β = −0.682, p = 0.033) through reductions in BMI levels, accounting for mediated proportions of 3.2%, 17.1%, and 8.5%, respectively. Furthermore, cheese intake provided a protective effect against ischemic stroke (β = −0.275, p = 0.003) by decreasing BMI and increasing HDL-C levels, with mediated proportions of 30.5% and 6.5%. Together, BMI and HDL-C accounted for 34.9% of the beneficial effect of cheese intake on reducing the risk of ischemic stroke. In contrast, an increased salt intake exhibited a positive association with large-artery ischemic stroke (β = 0.432, p = 0.033) through BMI elevation, with a mediated proportion of 10.9%. Conclusions: Our findings provide compelling evidence supporting causal relationships between dietary habits and stroke subtypes, while identifying mediators and evaluating the proportions of mediation. Adhering to a low-calorie, nutrient-dense diet enriched with dried fruits, cheese, and cereal, along with reduced salt and poultry consumption, could potentially mitigate stroke risk. Full article

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-β levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage. Full article

Antiretroviral therapy is capable of inhibiting HIV replication, but it fails to completely achieve a cure due to HIV persistence. The commonly used HIV cure approach is the “shock and kill” strategy, which employs latency-reversing agents to trigger viral reactivation and boost cellular immunity. Finding the appropriate drug combination for the “shock and kill” strategy would greatly facilitate clinical trials. The toll-like receptor (TLR) 7 agonist GS–9620 and nicotinamide (NAM) are reported as potential latency-reversing agents. Herein, we found the absence of viral reactivation when SHIV_SF162P3-aviremic rhesus macaques were treated with GS–9620 monotherapy. However, our findings demonstrate that viral blips emerged in half of the macaques treated with the combination therapy of GS–9620 and NAM. Notably, an increase in the reactivation of the replication-competent latent virus was measured in monkeys treated with the combination therapy. These findings suggest that the GS–9620 and NAM combination could be used as a multipronged HIV latency stimulation approach, with potential for optimizing antiviral therapy design. Full article

Aging is an inevitable physiological process accompanied by a decline in body physiology, including male fertility. A preparation from Ganoderma lucidum (GL) containing triterpenes and polysaccharides has been shown to have anti-aging properties. In the current study, the effects of GL on mating ability, testosterone secretion, and testicular structure and function were observed in middle-aged male mice. The GL preparation was administered orally to mice for 2 to 5 months, and then behavioral, serological, and histopathological examinations were performed. Results showed that in the GL group of mice, the mating latency was shortened, the number of pursuits within 20 min was increased, and the mating success rate was higher compared to control mice. Additionally, the levels of serum testosterone, cell proliferation (Ki67), and sperm-specific lactate dehydrogenase (LDH)-C4 were increased, while the levels of senescence-related protein p16 and cellular apoptosis were decreased in GL mice. Testicular spermatogenic cells and sperm and stromal cells were reduced and exhibited structural disorder in 11- and 14-month-old control mice, while these changes were improved compared to age-matched mice receiving the GL preparation. Furthermore, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and the pro-apoptotic protein Bax were decreased, while the anti-apoptotic protein Bcl-2 was increased in GL mice. Finally, the mitochondrial structure was relatively complete in GL mice compared to controls. Therefore, GL has the potential to improve testicular structure and function in middle-aged male mice by alleviating oxidative stress, maintaining mitochondrial homeostasis, and reducing cellular apoptosis. Full article

Recently, a series of highly effective peptide- or protein-based HIV fusion inhibitors have been identified. However, due to their short half-life, their clinical application is limited. Therefore, the development of long-acting HIV fusion inhibitors is urgently needed. Here, we designed and constructed a protein-based, long-acting HIV fusion inhibitor, termed FLT (FN3-L35-T1144), consisting of a monobody, FN3, which contains an albumin-binding domain (ABD), a 35-mer linker (L35), and a peptide-based HIV fusion inhibitor, T1144. We found that FLT bound, via its FN3 component, with human serum albumin (HSA) in a reversible manner, thus maintaining the high efficiency of T1144 against infection by both HIV-1 IIIB (X4) and Bal (R5) strains with IC₅₀ of 11.6 nM and 15.3 nM, respectively, and remarkably prolonging the half-life of T1144 (~27 h in SD rats). This approach affords protein-based HIV fusion inhibitors with much longer half-life compared to enfuvirtide, a peptide-based HIV fusion inhibitor approved for use in clinics. Therefore, FLT is a promising candidate as a new protein-based anti-HIV drug with an improved pharmacokinetic profile. Full article

Humans and wildlife are at risk from certain vector-borne diseases such as malaria, dengue, and West Nile and yellow fevers. Factors linked to global change, including habitat alteration, land-use intensification, the spread of alien species, and climate change, are operating on a global scale and affect both the incidence and distribution of many vector-borne diseases. Hence, understanding the drivers that regulate the transmission of pathogens in the wild is of great importance for ecological, evolutionary, health, and economic reasons. In this literature review, we discuss the ecological factors potentially affecting the transmission of two mosquito-borne pathogens circulating naturally between birds and mosquitoes, namely, West Nile virus (WNV) and the avian malaria parasites of the genus Plasmodium. Traditionally, the study of pathogen transmission has focused only on vectors or hosts and the interactions between them, while the role of landscape has largely been ignored. However, from an ecological point of view, it is essential not only to study the interaction between each of these organisms but also to understand the environmental scenarios in which these processes take place. We describe here some of the similarities and differences in the transmission of these two pathogens and how research into both systems may facilitate a greater understanding of the dynamics of vector-borne pathogens in the wild. Full article

BNT162b2 is a highly efficacious mRNA vaccine approved to prevent COVID-19. This brief report describes the immunogenicity and anti-viral protective effect of BNT162b2 in hACE2 transgenic mice. Prime-boost immunization with BNT162b2 elicited high titers in neutralizing antibodies against SARS-CoV-2, which correlated with viral clearance and alleviated lung lesions in these mice after viral challenge. Full article

Mycobacterium ulcerans is the causative agent of Buruli ulcer, also known in Australia as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and painless necrosis of the skin and soft tissue with the formation of large ulcers, commonly on the leg or arm. To date, 33 countries with tropical, subtropical and temperate climates in Africa, the Americas, Asia and the Western Pacific have reported cases of Buruli ulcer. The disease is rarely fatal, although it may lead to permanent disability and/or disfigurement if not treated appropriately or in time. It is the third most common mycobacterial infection in the world after tuberculosis and leprosy. The precise mode of transmission of M. ulcerans is yet to be elucidated. Nevertheless, it is possible that the mode of transmission varies with different geographical areas and epidemiological settings. The knowledge about the possible routes of transmission and potential animal reservoirs of M. ulcerans is poorly understood and still remains patchy. Infectious diseases arise from the interaction of agent, host and environment. The majority of emerging or remerging infectious disease in human populations is spread by animals: either wildlife, livestock or pets. Animals may act as hosts or reservoirs and subsequently spread the organism to the environment or directly to the human population. The reservoirs may or may not be the direct source of infection for the hosts; however, they play a major role in maintenance of the organism in the environment, and in the mode of transmission. This remains valid for M. ulcerans. Possums have been suggested as one of the reservoir of M. ulcerans in south-eastern Australia, where possums ingest M. ulcerans from the environment, amplify them and shed the organism through their faeces. We conducted a systematic review with selected key words on PubMed and INFORMIT databases to aggregate available published data on animal reservoirs of M. ulcerans around the world. After certain inclusion and exclusion criteria were implemented, a total of 17 studies was included in the review. A variety of animals around the world e.g., rodents, shrews, possums (ringtail and brushtail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have been recorded as being infected with M. ulcerans. The majority of studies included in this review identified animal reservoirs as predisposing to the emergence and reemergence of M. ulcerans infection. Taken together, from the selected studies in this systematic review, it is clear that exotic wildlife and native mammals play a significant role as reservoirs for M. ulcerans. Full article