Vitamin C functions as double-edge sword on cancer progression depending on ERK activation or inhibition mediated by its receptor SVCT2

The effect of Vitamin C (Vc) in oncotherapy was controversial for decades. And hyperactivation of extracellular signal-regulated kinase (ERK) drove tumorigenesis. Herein, we demonstrated that Vc activated ERK through sodium-dependent Vc transporter 2 (SVCT2), while high-dose Vc resulted in persistent ERK feedback inhibition following activation. Extracellular Vc binding to SVCT2 initiated ERK activation, then transmembrane transport of Vc induced dimerization of SVCT2. Activated ERK phosphorylated protein tyrosine phosphatase non-receptor type 12 (PTPN12) at Ser434 and inhibited PTPN12 activity, thus enhancing phosphorylation of Janus kinase 2 (JAK2), which phosphorylated growth factor receptor bound protein 2 (GRB2) at Tyr160 to promote GRB2 dimers dissociation and recruitment of GRB2 to SVCT2, leading to further ERK activation. Different cancers have different sensitivities to Vc, the dose effects of Vc on cancer phenotypes depended on that ERK was activated or inhibited. These findings suggest SVCT2 is a Vc receptor mediating the ERK-PTPN12-JAK2-GRB2-ERK positive feedback loop and a potential target for oncotherapy.

Double-edge sword roles of iron in driving energy production versus instigating ferroptosis

Iron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

Photothermal Therapy may be a Double-edge Sword by Inducing the Formation of Bacterial Antibiotic Tolerance

Photothermal nanoparticles are thought to be the most potential candidates against infectious disease, by disrupting cell membrane and inhibiting metabolism. However, subpopulation survived with this low-activity state may be endowed...

Teacher Perceptions About the Incorporation of Mobile Devices in a Costa Rican Secondary School

Despite many studies researching the increased use and potential effectiveness of mobile devices in secondary education (high school) classrooms, less research has examined teachers' perceptions around such use. Accordingly, this qualitative (phenomenological) study used semi-structured interviews to explore 10 secondary teachers' perceptions around the use of mobile devices in Costa Rican classrooms. Utilizing an interpretive phenomenological analysis (IPA) approach to analyze the data of participants' experiences, results from this study found (1) that Costa Rican secondary teachers had mixed perceptions about using mobile devices for the teaching and learning process and (2) that mobile devices seem a “double edge sword,” which, if not used appropriately in the classroom, can be more detrimental than beneficial for students' learning processes.

Thymus Gland: A Double Edge Sword for Coronaviruses

The thymus is the main lymphoid organ that regulates the immune and endocrine systems by controlling thymic cell proliferation and differentiation. The gland is a primary lymphoid organ responsible for generating mature T cells into CD4+ or CD8+ single-positive (SP) T cells, contributing to cellular immunity. Regarding humoral immunity, the thymic plasma cells almost exclusively secrete IgG1 and IgG3, the two main complement-fixing effector IgG subclasses. Deformity in the thymus can lead to inflammatory diseases. Hassall’s corpuscles’ epithelial lining produces thymic stromal lymphopoietin, which induces differentiation of CDs thymocytes into regulatory T cells within the thymus medulla. Thymic B lymphocytes produce immunoglobulins and immunoregulating hormones, including thymosin. Modulation in T cell and naive T cells decrement due to thymus deformity induce alteration in the secretion of various inflammatory factors, resulting in multiple diseases. Influenza virus activates thymic CD4+ CD8+ thymocytes and a large amount of IFNγ. IFNs limit virus spread, enhance macrophages’ phagocytosis, and promote the natural killer cell restriction activity against infected cells. Th2 lymphocytes-produced cytokine IL-4 can bind to antiviral INFγ, decreasing the cell susceptibility and downregulating viral receptors. COVID-19 epitopes (S, M, and N proteins) with ≥90% identity to the SARS-CoV sequence have been predicted. These epitopes trigger immunity for antibodies production. Boosting the immune system by improving thymus function can be a therapeutic strategy for preventing virus-related diseases. This review aims to summarize the endocrine-immunoregulatory functions of the thymus and the underlying mechanisms in the prevention of COVID-19.

Humor of the Leader: A Source of Creativity of Employees Through Psychological Empowerment or Unethical Behavior Through Perceived Power? The Role of Self-Deprecating Behavior

Although we use humor in our daily communication, there still needs to cognize its effects on the attitudes and behavior of the employees. Based on benign violation theory (BVT), the study proposes that leader's humor (LH) conveys social information about counter norms. The BVT has been amalgamated with social information processing theory (SIPT) to develop hypotheses assuming the consequences of LH on the attitude and behavior of the employees. This study hypothesizes that even though LH is linked positively with employee creativity via leader-member exchange and psychological empowerment in sequence (blessing path), it may also send information to the employees about the acceptability of norm violation. This perception ultimately leads to power perception and, causes unethical behavior in the series (curse path). Moreover, this study also postulates that leader's self-deprecating humor (LSDH) moderates these indirect effects by enhancing the blessing and reducing the curse, which emerged from LH. Quantitative data of 630 software engineers from software houses based in Pakistan provided support to test the hypotheses. The results demonstrate that LH is a double-edge sword that enhances blessing (creativity) as well as curse (employee unethical behavior), whereas LSDH augments the blessing and throttles back the curse. Theoretical and managerial implications have also been discussed.