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Toxicity is the main reason for the failure at
2023-10-08
Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele
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Previously we described that cadmium induces
2023-10-08
Previously, we described that cadmium induces a more pronounced, but not selective, cell death on primary cholinergic neurons from basal forebrain (Del Pino et al., 2014). Degeneration of septal cholinergic neurons from basal forebrain, as happens in AD, results in memory deficits (Scheiderer et al.
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br Acknowledgements MC and PD were funded by the Michael
2023-10-08
Acknowledgements MC and PD were funded by the Michael J Fox Foundation (Grant ID 9969). We would like to thank Pierluigi Saba, Francesco Traccis and Barbara Tuveri for their technical assistance. Introduction In the prostate, androgens play a crucial role in normal, BPH and cancerous growth b
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Double immunofluorescence staining of Gas and Axl with
2023-10-08
Double immunofluorescence staining of Gas6 and Axl with neuronal specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1), demonstrated that Gas6 and Axl are expressed by neurons, astrocytes and microglia/macrophages (Fig. 2). In
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br STAR Methods br Acknowledgments We thank Simcere
2023-10-08
STAR★Methods Acknowledgments We thank Simcere Pharmaceuticals, Nanjing, China, for providing a rabbit anti-VEGF neutralizing monoclonal antibody. We thank Dr. Schlisio in the Ludwig Institute for Cancer Research, Karolinska Institute, for assistance with hypoxia assay. Y.C.’s laboratory is sup
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The specific mechanism and neurotoxic A species
2023-10-08
The specific mechanism and neurotoxic Aβ ctep sale are yet to be elucidated, however recent studies have provided significant evidence for the amyloid channel hypothesis. These reports have established that relatively small oligomers ( Conflict of interest Acknowledgements This work was financ
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Several enzymes in serine and glycine metabolism have
2023-10-08
Several enzymes in serine and glycine metabolism have been proposed as biomarkers for cancer stage and prognosis. Phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), and serine hydroxymethyltransferase (SHMT) levels are high in TNBC and low in luminal-A breast cancers (Kim et a
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We found evidence of the interaction
2023-10-08
We found evidence of the interaction between AR and hemiacetals by evaluating the effect of glucose on l-idose reduction. l-idose was recently proposed as the best AR substrate able to mimic glucose [38]. This aldose is structurally very closely related to d-glucose, from which it differs only in th
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It could be hypothesized that the adiponectin system
2023-10-07
It could be hypothesized that the adiponectin system is regulated by gonadal steroid hormones. The lowest concentrations of adiponectin, AdipoR1 and AdipoR2 proteins in the endometrium and myometrium during the mid-luteal and late-luteal phases suggest that progesterone suppresses the expression of
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br Hyperadiponectinemia in disease conditions Other evidence
2023-10-07
Hyperadiponectinemia in disease conditions Other evidence indicates that hyperadiponectinemia does not necessarily always imply a healthy outcome. Indeed, a recent study suggested that hyperadiponectinemia occurs in various diseases. Given that the risk for AD and vascular dementia is increased i
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br Funding This work was supported by Arena
2023-10-07
Funding This work was supported by Arena Pharmaceuticals, Inc, San Diego, CA, USA. Introduction 5-hydroxytryptamine 1B (5-HT1B) receptors are widely distributed in the central nervous system (CNS); they have various modulatory functions in drug reinforcement, appetitive behaviors, stress, moo
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salt inducible kinase AdipoRon is an orally active synthetic
2023-10-07
AdipoRon is an orally active, synthetic small molecule that activates adiponectin receptor (AdipoR). It mimics the antidiabetic effects of adiponectin, exhibiting its effect through the activation of AMPK and PPARα pathways via AdipoR1 and AdipoR2, respectively (Fig. 2) [62]. AdipoR activation has r
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br Introduction Epilepsy is characterized by
2023-10-07
Introduction Epilepsy is characterized by spontaneous recurrent seizures and represents one of the most frequent neurological diseases affecting about 60 million people worldwide (McNamara, 1999). It is estimated that up to 50% of all cases are triggered by “initial precipitating injuries”, such
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Patients with AAG often respond to intravenous
2023-10-07
Patients with AAG often respond to intravenous immunoglobulin or plasma exchange. If these therapies are inadequate, ongoing immune suppression with steroids, azathioprine, mycophenylate or rituximab have been shown to be effective in case reports. Our patient seemed initially resistant to steroid t
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Tacrine an aminoacridine derivative Fig A
2023-10-07
Tacrine, an aminoacridine derivative (Fig. 1, A), was the first AChE inhibitor approved for treatment of AD [12], [13]. This compound was withdrawn from the market due to its hepatotoxicity [14]. In spite of tacrine's side effects, it is still an attractive lead compound for medicinal chemists due t
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