Targeting autophagy for breast cancer prevention and therapy: From classical methods to phytochemical agents
Breast cancer is a heterogeneous illness comprising diverse biological subtypes, each of which differs in incidence, response to therapies, and prognosis. Despite the presence of novel medications that effectively target vital cellular signaling pathways and their application in clinical practice, breast cancer can still develop resistance to therapies by various mechanisms. Autophagy is a conserved catabolic cellular process that maintains intracellular metabolic homeostasis by removing dysfunctional or unnecessary cellular materials to recycle cytosolic components. This process serves as an adaptive survival response to diverse stress stimuli, thereby contributing to tumor initiation, progression, and drug resistance, leading to restriction of the effectiveness of chemotherapeutic treatments. Regarding this potential role of autophagy, molecular regulation and signal transduction of this process represent an attractive approach to combat cancer development and drug resistance. Among various therapeutic agents, bioactive plant-derived compounds have received significant interest as promising anticancer drugs. A plethora of evidence has shown that phytochemicals with the capacity to modulate autophagy may have the potential to be used as inhibitors of breast cancer growth. In this review, we describe recent findings on autophagy targeting along with conventional methods for breast cancer therapy. Subsequently, we introduce phytochemical compounds with the capacity to modulate autophagy for breast cancer treatment.
Baicalein blocked gastric cancer cell proliferation and invasion through modulated platelet type 12-lipoxygenase
Baicalein (BAI) is one of the main ingredients of georgi. Its pharmacological effects have been widely reported in various cancers. However, the specific molecular mechanism of BAI in gastric cancer (GC) has not been defined. This study investigates BAI's inhibitory effect on gastric cancer and its potential mechanisms.
Genistein inhibits the release of pro-inflammatory substances from macrophages by suppressing potassium loss- and ROS-mediated caspase-1/gasdermin D pathway activation and pyroptotic cell lysis
The expression of pro-inflammatory substances is closely related to various diseases. Genistein (GEN), a soy isoflavone, has been proven to inhibit the production of pro-inflammatory substances in macrophages. This study aimed to determine whether GEN exerts its inhibitory effect on the expression of pro-inflammatory substances by suppressing the release of these substances via attenuating pyroptotic cell lysis.
Neuroprotective effects of walnut in nervous system disorders: A comprehensive review
Juglans regia L. (walnut) has a rich history in traditional medicine due to its various medicinal properties, including its neuroprotective effects on nervous system disorders. This updated review sheds light on the therapeutic potential of walnuts in nervous system disorders such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, and pain, supported by evidence from in vivo and in vitro studies. These beneficial effects are attributed to the walnut's rich composition of bioactive compounds, including gallic acid, protocatechuic acid, ferulic acid, sinapate, ellagic acid, p-hydroxybenzoic acid, p-coumaric acid, quercetin 3-galactoside, juglone, vanillic acid, quercetin, myricetin, kaempferol, apigenin, luteolin, daidzein, and others. The mechanisms underlying the neuroprotective effects of walnuts include decreasing oxidative stress, inflammation, apoptosis, proteolysis, β-amyloid plaque accumulation, acetylcholinesterase (AChE) activity, phosphorylated-c-Jun N-terminal kinase (p-JNK) levels, increasing adenosine triphosphate (ATP) levels, mitochondrial homeostasis, expression of mitophagy-related proteins, and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (KEAP1)/heme oxygenase-1 (HO-1) pathway. Although walnuts hold great promise in managing nervous system disorders and their complications, further preclinical and clinical investigations are necessary to consolidate these findings. This comprehensive review highlights the potential of walnuts as a natural therapeutic agent and encourages future research to unlock their full neuroprotective potential.
Effect of mild gestational diabetes mellitus on histological, ultrastructural, and quantitative morphometric alterations of rat fetal liver
Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue.
Anti-oxidant and anti-apoptotic effects of royal jelly against polystyrene microplastic-induced testicular injury in mice
In recent years, microplastics (MPs), which are novel environmental contaminants measuring 5 mm in diameter, have garnered considerable attention. However, information regarding substances that can mitigate the dangers of MPs for animals remains extremely limited.
Doxorubicin-loaded NK exosomes enable cytotoxicity against triple-negative breast cancer spheroids
Natural killer (NK) cells are the most professional innate immune cells that initiate extracellular apoptosis via cytotoxic granules in malignant cells. Antitumoral properties of NK-derived exosomes (Exos) are attributed to their parent cells. Loading drugs into Exos as a carrier can enhance their effect and enable targeted delivery. In the present study, we aim to deliver Doxorubicin (DOX) to the breast cancer spheroids by NK-Exos.
Quercetin is a foe in the heart by targeting the hERG potassium channel
Quercetin is a plant flavonoid known for its pharmacological activities, such as antioxidant, anti-inflammatory, and anti-cancer properties. However, there is limited information available regarding its potential toxicities. A previous study showed that quercetin can inhibit human ether-a-go-related gene (hERG, also named KCNH2) currents, which may lead to long QT syndrome, torsade de pointes (TdP), and even sudden cardiac death. This study aimed to investigate the effects of quercetin on hERG and its potential mechanism.
Zinc oxide nanoparticle-reinforced sodium alginate/hydroxyapatite scaffolds for osteoporosis treatment in fragility fracture patients: Development and characterization using artificial neural networks (ANNs) modeling
Osteoporosis is a significant public health concern due to its association with fragility fractures. Despite experiencing such fractures, many patients remain at high risk of future fractures due to inadequate management and treatment of their underlying osteoporosis. This research presents a comprehensive intervention to enhance osteoporosis management in patients with fragility fractures. The intervention involves a thorough personalized assessment of fracture risk using clinical factors and bone density testing, followed by customized treatment based on the individual's fracture risk level. It also addresses non-compliance through patient education, counseling, reminders, and improved care coordination among acute, primary, and specialty providers.
Isorhamnetin alleviates symptoms and inhibits oxidative stress levels in rats with pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease with high mortality. Isorhamnetin (ISO), one of the main natural flavonoids extracted from sea buckthorn, has pharmacological effects such as anti-inflammatory, anti-proliferative and antioxidant. This study aimed to investigate the protective effect of ISO on PAH and its relationship with the phosphorylation of the c-Src tyrosine kinase (p-c-src)/NOX1 signaling pathway.
Evening primrose oil ameliorates tissue architecture, apoptosis, and oxidative stress in the pancreas of diabetic rats: Possible role of miR-21
Activating apoptosis and oxidative stress contributes to the pathogenesis of diabetes. Evening primrose oil (EPO) has been shown to regulate lipid profiles and hyperglycemia under metabolic conditions. This study aimed to examine the effect of EPO on miR-21 expression, oxidative stress, apoptosis, and histological changes in the pancreas of male rats with experimental diabetes induced by streptozotocin (STZ).
High-intensity interval training combined with cannabidiol supplementation improves cognitive impairment by regulating the expression of apolipoprotein E, presenilin-1, and glutamate proteins in a rat model of amyloid β-induced Alzheimer's disease
Alzheimer's disease (AD) is a major public concern and one of the primary types of dementia characterized by memory impairment and cognitive decline. Although the properties of exercise training and cannabidiol (CBD) treatments for improving AD have recently been revealed, the exact mechanisms remain unknown. Therefore, this study highlights the interactive impact of high-intensity interval training (HIIT) and CBD administration on improving cognitive impairment in a rat model of amyloid beta (Aꞵ)-induced AD through modulating the expression of apolipoprotein E (APOE), presenilin-1, and glutamate proteins.
The simultaneous use of CRISPR/Cas9 to knock out the PI3Kca gene with radiation to enhance radiosensitivity and inhibit tumor growth in breast cancer
Breast neoplasm is a malignancy that can have a poor prognosis. The PI3K/AKT signaling pathway is frequently activated in various tumor types, including breast cancer, leading to alterations in the tumor microenvironment and radioresistance. Selective inhibition of PI3Kca (p110α) has been considered an alternative approach to overcome radioresistance, owing to concerns surrounding the excessive side effects of pan-PI3K inhibitors tested in clinical trials. This investigation aimed to evaluate the efficacy of co-administering PI3Kca knocking out with radiation therapy in mitigating radioresistance and suppressing tumor growth in the MDA-MB-231 cell line.
Vitamin C, doxycycline, and azithromycin (VDA) targeted changes in cellular senescence-related genes in human adipose-derived mesenchymal stem cells
Adipose-derived Mesenchymal stem cells (ASCs) have garnered attention for their regenerative potential; therefore, their cellular senescence-related gene expression remains crucial in therapeutic contexts. Nowadays, combination therapies have shown promising results in reducing senescent cells. This study investigated the effects of vitamin C, doxycycline, and azithromycin co-treatment on the key cellular senescence-associated genes in ASCs.
Taurine supplementation decreases fat accumulation by suppressing FAS and enhancing ATGL through the ATGL pathway
Obesity leads to severe health issues like cardiovascular disease. Natural substances with anti-obesity properties are gaining attention. This study investigates the impact of taurine on lipid levels in rats fed a high-fat diet.
Saroglitazar suppresses KIM-1 and type IV collagen in high fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats
Nephropathy is the most common comorbidity linked to T2D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.
Regenerative role of mast cells and mesenchymal stem cells in histopathology of the sciatic nerve and tibialis cranialis muscle, following denervation in rats
Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells.
Apatinib has anti-tumor effects and induces autophagy in lung cancer cells with high expression of VEGFR-2
This study investigated the inhibitory effect of apatinib on lung cancer cells with high expression of vascular endothelial growth factor-2 (VEGFR-2) and on inducing cellular autophagy and drug resistance.
Catalpol alleviates amyloid- generation and neuronal oxidative stress injury via activating the Keap1-Nrf2/ARE signaling pathway in the immortalized lymphocytes from patients with late-onset Alzheimer's disease and SKNMC cells co-culture model
To assess the effect of catalpol, the major bioactive constituents of , on our Alzheimer's disease (AD) model.
Total flavonoids of (P. Beauv.) Spring ameliorates diabetes-induced acute lung injury via activating Nrf2/HO-1
This investigation explored the mechanism by which the total flavonoids of (P.Beauv.) Spring (TFST) mitigate oxidative stress through the activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), thereby ameliorating acute lung injury (ALI) induced by diabetes.
Crocin from saffron ameliorates allergic airway inflammation through NF-κB, IL-17, and Nrf2/HO-1 signaling pathways in mice
Asthma is a complex inflammatory disorder with the infiltration of inflammatory cells in the lung airways. Saffron's active component, crocin, has been proven to possess anti-inflammatory and anti-oxidant effects. The objective of this current study was to explore the impact of crocin on NF-kB and nuclear erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathways in ovalbumin (OVA)-sensitized mice, aiming to understand its mechanism.