Coral-virus interactions: A double-edged sword?

Marine viruses were little studied until 1989, when they were discovered to be extremely abundant in the sea. Virology is now a growing field of science in coral reef research, largely related to an increase in the frequency of coral bleaching events and other coral diseases. Because viruses are obligate symbionts, they are generally perceived as parasitic and harmful to their hosts. However, evidence that viruses confer benefits to their hosts is growing and their role as mutualists is emerging. Here we review both the detrimental and beneficial aspects of viral infections and argue that as the field of coral virology expands, in addition to their pathogenicity, the idea that viruses represent functionally beneficial components of the coral holobiont be considered.     

The possible double-edged sword effects of vitamin D on COVID-19: A hypothesis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor-β. A higher IgA, Th2/Th1 ratio, and T-regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double-edged sword in COVID-19. Although VitD supplementation might be highly recommended in COVID-19, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID-19.     

Endosteal stem cells at the bone-blood interface: A double-edged sword for rapid bone formation

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non-endosteal perisinusoidal niche. Single-cell molecular profiling and in vivo cell lineage analyses play key roles in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor-making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast-chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell-like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation.     

Ketone bodies: A double-edged sword for mammalian life span

Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role of endogenous ketogenesis in mammalian life span, and the safety and efficacy of the long-term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole-body Hmgcs2 deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3-butanediol, a precursor of β-hydroxybutyrate. Furthermore, feeding the 1,3-butanediol-containing diet from early in life increases midlife mortality in normal mice, but in aged mice it extends life span and prevents the high mortality associated with atherosclerosis in ApoE-deficient mice. By contrast, an ad libitum low-carbohydrate ketogenic diet markedly increases mortality. In conclusion, endogenous ketogenesis affects mammalian survival, and ketone body supplementation may represent a double-edged sword with respect to survival, depending on the method of administration and health status.     

Akt: A double-edged sword for hematopoietic stem cells

The phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway is dysregulated in a wide range of malignancies, including leukemia, and several members of this pathway are attractive therapeutic targets in oncology1. Although Akt is constitutively phosphorylated in up to 90% of cases of acute myeloid leukemia (AML), its role in AML has been unclear2. In some cases, Akt activation is attributed to activation of tyrosine kinases, such as BCR-ABL or FLT3-ITD, but in many cases the mechanism of Akt phosphorylation and its significance is unknown. Is AKT activation simply a marker of leukemic transformation, or is it a driver of leukemogenesis?     

Cytotoxic and cytoprotective effects of tryptamine-4,5-dione on neuronal cells: a double-edged sword

Serotonin (5-hydroxytryptamine) is a putative substrate for myeloperoxidase, which may convert it into the reactive quinone tryptamine-4,5-dione (TD). In this study, we found that the viability of human SH-SY5Y neuroblastoma cells treated with 25?μM TD was increased to approximately 117%. On the other hand, the cell viability was significantly decreased by exposure to TD (150–200?μM), with an increase in intracellular reactive oxygen species (ROS). Interestingly, pre-treatment of SH-SY5Y cells with 100?μM TD prevented cell death and suppressed intracellular ROS generation evoked by the addition of hydrogen peroxide (H₂O₂). Expression of the phase-II antioxidant enzyme NAD(P)H: quinone oxidoreductase 1 and haem oxygenase 1 were upregulated by TD at a concentration of 50–100?μM. Nuclear factor erythroid 2-related factor 2 (Nrf2), the regulator of these enzyme, was translocated from the cytosol to the nucleus by 100?μM TD. In summary, moderate concentrations of TD may increase the self-defence capacity of neuronal cells against oxidative stress.     

Signalling pathways of the TNF superfamily: a double-edged sword

Two different tumour-necrosis factors (TNFs), first isolated in 1984, were found to be cytotoxic to tumour cells and to induce tumour regression in mice. Research during the past two decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors. These ligands, while regulating normal functions such as immune responses, haematopoiesis and morphogenesis, have also been implicated in tumorigenesis, transplant rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis and diabetes; so indicating their role as 'double-edged swords'. These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries.     

Role of JNK activation in apoptosis： A double-edged sword

JNK is a key regulator of many cellular events, including programmed cell death (apoptosis). In the absence of NF-κB activation, prolonged JNK activation contributes to TNF-α induced apoptosis. JNK is also essential for UV induced apoptosis. However, recent studies reveal that JNK can suppress apoptosis in IL-3-dependent hematopoietic cells via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Thus, JNK has pro- or antiapoptotic functions, depending on cell type, nature of the death stimulus, duration of its activation and the activity of other signaling pathways.     

Melatonin-mediated regulation of autophagy: Making sense of double-edged sword in cancer

Much research has been conducted to discover novel techniques to reverse the process of tumorigenesis and, cure already stablished malignancies. One well-stablished approach has been the use of organic compounds and naturally found agents such as melatonin whose anticancer effects have been shown in multiple studies, signaling a unique opportunity regarding cancer prevention and treatment. Various agents use a variety of methods to exert their anticancer effects. Two of the most important of these methods are interfering with cell signaling pathways and changing cellular functions, such as autophagy, which is essential in maintaining cellular stability against multiple exogenous and endogenous sources of stress, and is a major tool to evade early cell death. In this study, the importance of melatonin and autophagy are discussed, and the effects of melatonin on autophagy, and its contribution in the process of tumorigenesis are then noted.     

A double-edged sword: parental care increases risk of offspring infection by a maternally vectored parasite

Parental care can protect offspring from predators but can also create opportunities for parents to vector parasites to their offspring. We hypothesized that the risk of infection by maternally vectored parasites would increase with the frequency of mother–offspring contact. Ammophila spp. wasps (Hymenoptera: Sphecidae) build nests in which they rear a single offspring. Ammophila species exhibit varied offspring provisioning behaviours: some species enter the nest once to provision a single, large caterpillar, whereas others enter the nest repeatedly to provision with many smaller caterpillars. We hypothesized that each nest visit increases the risk of offspring parasitism by Paraxenos lugubris (Strepsiptera: Xenidae), whose infectious stages ride on the mother wasp (phoresy) to reach the vulnerable Ammophila offspring. We quantified parasitism risk by external examination of museum-curated Ammophila specimens—the anterior portion of P. lugubris protrudes between the adult host''s abdominal sclerites and reflects infection during the larval stage. As predicted, Ammophila species that receive larger numbers of provisions incur greater risks of parasitism, with nest provisioning behaviour explaining ca 90% of the interspecific variation in mean parasitism. These findings demonstrate that parental care can augment, rather than reduce, the risk of parasite transmission to offspring.     

Alternative pathways of NF-kappaB activation: a double-edged sword in health and disease

While the classical pathway of NF-kappaB activation plays critical roles in a wide range of biological processes, the more recently described "non-canonical" NF-kappaB pathway has important but more restricted roles in both normal and pathological processes. The non-canonical NF-kappaB pathway, based on processing of the nf-kappab2 gene product p100 to generate p52, appears to be involved in B-cell maturation and lymphoid development. Deregulated activation of this pathway has been observed in a variety of malignant and autoimmune diseases, thus inhibitors that specifically target p100 processing might be predicted to have potential roles as immunomodulators and in the therapy of malignant diseases. We review current understandings of NF-kappaB activation, particularly the mechanisms of p100 processing under both physiological and pathological conditions.     

Giardia duodenalis: The double-edged sword of immune responses in giardiasis

Giardiasis is one of the most common intestinal protozoan infections worldwide. The etiological agent, Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis), is a flagellated, binucleated protozoan parasite which infects a wide array of mammalian hosts (Adam, 2001). The symptoms of giardiasis include abdominal cramps, nausea, and acute or chronic diarrhea, with malabsorption and failure of children to thrive occurring in both sub-clinical and symptomatic disease (Thompson et al., 1993). Infections are transmitted by cysts which are excreted in the feces of infected humans and animals. Human giardiasis is distributed worldwide, with rates of detection between 2-5% in the developed world and 20-30% in the developing nations (Farthing, 1994). There is significant variation in the outcome of Giardia infections. Most infections are self-limiting, although re-infection is common in endemic areas and chronic infections also occur. Moreover, some individuals suffer from severe cramps, nausea and diarrhea while others escape these overt symptoms. This review will describe recent advances in parasite genetics and host immunity that are helping to shed light on this variability.     

病毒感染引起的炎症反应：宿主对抗病毒的“双刃剑”

先天性免疫系统作为宿主抵抗外来病原入侵的第一道防线,也是最迅速的防御系统。宿主先天性免疫系统中的模式识别受体识别入侵信号并激活炎症信号通路,诱导产生大量促炎性细胞因子,引起炎症反应。病毒感染是激活炎症反应的条件之一,诱导机体产生强烈的免疫应答,强大的炎症反应调控网络在宿主抗病毒过程中发挥关键作用,以维持机体的平衡。本文综述了病毒感染引起的炎症反应,重点介绍了宿主对炎症反应的调控网络,以及DNA和RNA病毒对炎症反应的调节机制,为病毒感染引起的免疫性疾病的治疗提供参考。     

Chirality induction in supramolecular aggregate: chiral recognition between armed cyclen-Na+ complexes having quadruplicated helical geometry

A water-soluble self-aggregate of octadentate Na+ complex with chiral cholesterol-armed cyclen provides unique microenvironments for chirality induction of guest cyclen-Na+ complex via supramolecular interaction.     

To be or not to be: The double-edged sword roles of liver progenitor cells

Given the liver's remarkable and unique regenerative capacity, researchers have long focused on liver progenitor cells (LPCs) and liver cancer stem cells (LCSCs). LPCs can differentiate into both hepatocytes and cholangiocytes. However, the mechanism underlying cell conversion and its distinct contribution to liver homeostasis and tumorigenesis remain unclear. In this review, we discuss the complicated conversions involving LPCs and LCSCs. As the critical intermediate state in malignant transformation, LPCs play double-edged sword roles. LPCs are not only involved in hepatic wound-healing responses by supplementing liver cells and bile duct cells in the damaged liver but may transform into LCSCs under dysregulation of key signaling pathways, resulting in refractory malignant liver tumors. Because LPC lineages are temporally and spatially dynamic, we discuss crucial LPC subgroups and summarize regulatory factors correlating with the trajectories of LPCs and LCSCs in the liver tumor microenvironment. This review elaborates on the double-edged sword roles of LPCs to help understand the liver's regenerative potential and tumor heterogeneity. Understanding the sources and transformations of LPCs is essential in determining how to exploit their regenerative capacity in the future.