Multi-faced neuroprotectice effects of Ginsenoside Rg1 in an Alzheimer mouse model

There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12–13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment

Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction

Mitochondrial dysfunction is one of the major pathological changes seen in Alzheimer's disease (AD). Amyloid beta-peptide (Aβ), a neurotoxic peptide, accumulates in the brain of AD subjects and mediates mitochondrial and neuronal stress. Therefore, protecting mitochondrion from Aβ-induced toxicity holds potential benefits for halting and treating and perhaps preventing AD. Here, we report that administration of ginsenoside Rg1, a known neuroprotective drug, to primary cultured cortical neurons, rescues Aβ-mediated mitochondrial dysfunction as shown by increases in mitochondrial membrane potential, ATP levels, activity of cytochrome c oxidase (a key enzyme associated with mitochondrial respiratory function), and decreases in cytochrome c release. The protective effects of Rg1 on mitochondrial dysfunction correlate to neuronal injury in the presence of Aβ. This finding suggests that ginsenoside Rg1 may attenuate Aβ-induced neuronal death through the suppression of intracellular mitochondrial oxidative stress and may rescue neurons in AD

Multi-faced neuroprotectice effects of Ginsenoside Rg1 in an Alzheimer mouse model

There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12–13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment

Workplace Learning in China: Transferring Training Into Practice to Improve Performance

Purpose: The present study seeks to examine the efficacy of different training modalities on increasing workplace learning, representatives' intent to transfer what they learned into their work, and importantly how training impacts actual work performance. These relationships are tested in the context of a Chinese division of a multinational pharmaceutical company, where pharmaceutical representatives are tasked with relaying relevant efficacy and safety information on pharmaceutical products to health care professionals who prescribe them to patients. Methods: The present study employed a three-group between-subjects experimental design. Representatives received varying forms of training (instruction only, instruction plus reflection, and instruction, reflection, plus direct feedback) based on experimental conditions. After three training sessions over the course of six weeks, representatives were assessed on how much they learned in the training and their actual work performance through observer assessment of meetings with health care professionals, facilitated by the representatives. Findings: In this study, it was found that the process of actively reflecting on what was learned in training led to increased learning, as well as increased performance, compared to simply studying the material. However, receiving direct feedback on training performance, combined with active reflection training, did not provide any further benefits in terms of learning or work performance. Notably, there were no differences in intent to transfer learned material to work, as all conditions reported high levels of transfer intention. Conclusion: The finding provides insightful evidence to support the benefits of fostering trainees' active reflections for work-based learning in the Chinese industry training scenario. In contrast, receiving direct comments on how students performed from a manager or trainer, as well as advise on how do better in the future, had no effect on increasing learning or performance. Although the effect of direct feedback is not statistically significant in this context, further research should be done in understanding individuals' thoughts and behaviors when received direct feedbacks received in workplace training. Relatively little workplace research has assessed both workplace learning and performance in the same study, specifically in the Chinese context. While training efficacy likely varies across cultures to begin with, compensation structures in China do not provide the same monetary incentives for workplace learning (i.e. chance to increase income) as Western culture. This means that any way to increase workplace learning should be of extra value, as employees otherwise may not engage in it at all.

Workplace learning in China: transferring training into practice to improve performance

Purpose: The present study seeks to examine the efficacy of different training modalities on increasing workplace learning, representatives\u27 intent to transfer what they learned into their work, and importantly how training impacts actual work performance. These relationships are tested in the context of a Chinese division of a multinational pharmaceutical company, where pharmaceutical representatives are tasked with relaying relevant efficacy and safety information on pharmaceutical products to health care professionals who prescribe them to patients. Methods: The present study employed a three-group between-subjects experimental design. Representatives received varying forms of training (instruction only, instruction plus reflection, and instruction, reflection, plus direct feedback) based on experimental conditions. After three training sessions over the course of six weeks, representatives were assessed on how much they learned in the training and their actual work performance through observer assessment of meetings with health care professionals, facilitated by the representatives. Findings: In this study, it was found that the process of actively reflecting on what was learned in training led to increased learning, as well as increased performance, compared to simply studying the material. However, receiving direct feedback on training performance, combined with active reflection training, did not provide any further benefits in terms of learning or work performance. Notably, there were no differences in intent to transfer learned material to work, as all conditions reported high levels of transfer intention. Conclusion: The finding provides insightful evidence to support the benefits of fostering trainees\u27 active reflections for work-based learning in the Chinese industry training scenario. In contrast, receiving direct comments on how students performed from a manager or trainer, as well as advise on how do better in the future, had no effect on increasing learning or performance. Although the effect of direct feedback is not statistically significant in this context, further research should be done in understanding individuals\u27 thoughts and behaviors when received direct feedbacks received in workplace training. Relatively little workplace research has assessed both workplace learning and performance in the same study,specifically in the Chinese context. While training efficacy likely varies across cultures to begin with, compensation structures in China do not provide the same monetary incentives for workplace learning (i.e. chance to increase income) as Western culture. This means that any way to increase workplace learning should be of extra value, as employees otherwise may not engage in it at all. (DIPF/Orig.

Ferroptosis in hematological malignant tumors

Ferroptosis is a kind of iron-dependent programmed cell death discovered in recent years. Its main feature is the accumulation of lipid reactive oxygen species in cells, eventually leading to oxidative stress and cell death. It plays a pivotal role in normal physical conditions and the occurrence and development of various diseases. Studies have shown that tumor cells of the blood system, such as leukemia cells and lymphoma cells, are sensitive to the response to ferroptosis. Regulators that modulate the Ferroptosis pathway can accelerate or inhibit tumor disease progression. This article reviews the mechanism of ferroptosis and its research status in hematological malignancies. Understanding the mechanisms of ferroptosis could provide practical guidance for treating and preventing these dreaded diseases

Treadmill Exercise Ameliorates Depression-Like Behavior in the Rats With Prenatal Dexamethasone Exposure: The Role of Hippocampal Mitochondria

Prenatal exposure to synthetic glucocorticoids (sGCs) can increase the risk of affective disorders, such as depression, in adulthood. Given that exercise training can ameliorate depression and improve mitochondrial function, we sought to investigate whether exercise can ameliorate depression-like behavior induced by prenatal sGC exposure and mitochondria function contributes to that behavior. At first, we confirmed that prenatal dexamethasone (Dex) administration in late pregnancy resulted in depression-like behavior and elevated level of circulatory corticosterone in adult offspring. We then found that mRNA and protein expression of a number of mitochondrial genes was changed in the hippocampus of Dex offspring. Mitochondria in the hippocampus showed abnormal morphology, oxidative stress and dysfunction in Dex offspring. Intracerebroventricular (ICV) injection of the mitochondrial superoxide scavenger mitoTEMPO significantly alleviated depression-like behavior but did not significantly affect circulatory corticosterone level in Dex offspring. The adult Dex offspring treated with treadmill exercise starting at four-weeks of age showed ameliorated depressive-like behavior, improved mitochondrial morphology and function and reduced circulatory corticosterone level. Our data suggest mitochondria dysfunction contributes to depression-like behavior caused by prenatal sGC exposure. Intervention with exercise training in early life can reverse depression caused by prenatal Dex exposure, which is associated with improvement of mitochondrial function in the hippocampus

Alterations in cellular metabolisms after TKI therapy for Philadelphia chromosome-positive leukemia in children: A review

Incidence rates of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) are lower but more aggressive in children than in adults due to different biological and host factors. After the clinical application of tyrosine kinase inhibitor (TKI) blocking BCR/ABL kinase activity, the prognosis of children with CML and Ph+ ALL has improved dramatically. Yet, off-target effects and drug tolerance will occur during the TKI treatments, contributing to treatment failure. In addition, compared to adults, children may need a longer course of TKIs therapy, causing detrimental effects on growth and development. In recent years, accumulating evidence indicates that drug resistance and side effects during TKI treatment may result from the cellular metabolism alterations. In this review, we provide a detailed summary of the current knowledge on alterations in metabolic pathways including glucose metabolism, lipid metabolism, amino acid metabolism, and other metabolic processes. In order to obtain better TKI treatment outcomes and avoid side effects, it is essential to understand how the TKIs affect cellular metabolism. Hence, we also discuss the relevance of cellular metabolism in TKIs therapy to provide ideas for better use of TKIs in clinical practice