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During exercise circulatory adjustments to meet oxygen demands are mediated by multiple autonomic mechanisms, the skeletal muscle exercise pressor reflex (EPR), the baroreflex (BR), and by feedforward signals from central command neurons in higher brain centers. Insulin resistance in peripheral tissues includes sensitization of skeletal muscle afferents by hyperinsulinemia which is in part responsible for the abnormally heightened EPR function observed in diabetic animal models and patients. However, the role of insulin signaling within the central nervous system (CNS) is receiving increased attention as a potential therapeutic intervention in diseases with underlying insulin resistance.

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The Role of Endogenous Beta-Endorphin and Enkephalins in the Crosstalk Between Ethanol and Morphine.

Pharmaceuticals (Basel)

January 2025

Department of Biotechnology and Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.

There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol, by causing the release of opioid peptides, may sensitize the system to the action of exogenous opioids such as morphine.

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New Promising Steroidal Aromatase Inhibitors with Multi-Target Action on Estrogen and Androgen Receptors for Breast Cancer Treatment.

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UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.

Endocrine therapies that comprise anti-estrogens and aromatase inhibitors (AIs) are the standard treatment for estrogen receptor-positive (ER+) (Luminal A) breast cancer-the most prevalent subtype. However, the emergence of resistance restricts their success by causing tumor relapse and re-growth, which demands a switch towards other therapeutic approaches in order to minimize or overcome resistance. Indeed, this clinical limitation highlights the search for new molecules to improve cancer treatment.

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Neuron Modulation by Synergetic Management of Redox Status and Oxidative Stress.

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January 2025

Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Academy for Engineering and Technology, Fudan University, Shanghai, 200433, P. R. China.

The transient receptor potential (TRP) channel is a key sensor for diverse cellular stimuli, regulating the excitability of primary nociceptive neurons. Sensitization of the TRP channel can heighten pain sensitivity to innocuous or mildly noxious stimuli. Here, reversible modulation of TRP channels is achieved by controlling both the light-induced photoelectrochemical reaction to induce neuronal depolarization, and antioxidants for neuronal protection.

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Immunization plays a substantial role in reducing the under-five mortality rate. However, Tanzania still has a significant number of zero-dose and under-vaccinated children and was ranked among the top ten African countries with the highest numbers of zero-dose children in 2022. The human-centered design (HCD) approach is more ethical and effective at addressing public health challenges in complex sociocultural settings.

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