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Alzheimer's disease (AD) is a degenerative disease of the central nervous system that is the most common type of senile dementia. Ferroptosis is a new type of iron-dependent programmed cell death identified in recent years that is different from other cell death forms. Ferroptosis is induced by excessive accumulation of lipid peroxides and reactive oxygen species (ROS) in cells. In recent years, it has been found that ferroptosis plays an important role in the pathological process of AD. Iron dyshomeostasis contribute to senile plaques (SP) deposition and neurofibrillary tangles (NFTs). Iron metabolism imbalance in brain and the dysfunction of endogenous antioxidant systems including system Xc- and glutathione peroxidase (GPX) are closely related to the etiopathogenesis of AD. Dysfunction of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy induced ferroptosis can accelerates the pathological process of AD. In addition, NRF2, through regulating the expression of a considerable number of genes related to ferroptosis, including genes related to iron and glutathione metabolism, plays an important role in the development of AD. Here, we review the potential interaction between AD and ferroptosis and the major pathways regulating ferroptosis in AD. We also review the active natural and synthetic compounds such as iron chelators, lipid peroxidation inhibitors and antioxidants available to treat AD by alleviating iron dyshomeostasis and preventing ferroptosis in mice and cell models to provide valuable information for the future treatment and prevention of AD.Microtubule-targeting (MT) drugs taxanes and vinca alkaloids are widely used as chemotherapeutic agents against different tumors for more than 30 years because of their ability to block mitotic progression by disrupting the mitotic spindle and activating the spindle assembly checkpoint (SAC) for a prolonged period of time. However, responses to mitotic arrest are different-some cells die during mitotic arrest, whereas others undergo mitotic slippage and survive becoming able for proliferation. Using normal fibroblasts and several cancer cell types we determined two critical doses, T1 and T2, of mitotic inhibitors (nocodazole, Taxol, and vinorelbine). T1 is the maximal dose cells can tolerate undergoing normal division, and T2 is the minimal mitostatic dose, wherein > 90% of mitotic cells are arrested in mitosis. In all studied cell lines after treatment with mitotic inhibitors in a dose above T2 cells had entered mitosis either die or undergo mitotic slippage. We show that for all three drugs used cell death totic inhibitors and inhibitors of Bcl-xL anti-apoptotic protein will be efficient only if the Bcl-xL inhibitor will be added before mitotic slippage occurs or soon afterward. The combined treatment proposed might be an efficient approach to anti-cancer therapy.[This corrects the article DOI 10.3389/fphar.2021.710778.].Ethnopharmacological relevance Pien-Tze-Huang (PZH)-a traditional Chinese medicine (TCM) compound-has been employed to treat various liver inflammation and tumors for over 10 decades. Interestingly, most of the pharmacological effects had been validated and explored toward liver ailment along with pro-inflammatory conditions and cancer at the cellular and molecular level to date. Aim of the study The present study aimed to investigate the therapeutic effect of PZH on autophagy and TGF-β1 signaling pathways in rats with liver fibrosis and hepatic stellate cell line (HSC). Materials and methods Male SD rats with carbon tetrachloride (CCl4)-induced liver fibrosis were used as the animal model. Next, PZH treatment was given for 8 weeks. Afterward, the therapeutic effects of PZH were analyzed through a hepatic tissue structure by hematoxylin-eosin (H&E), Van Gieson (VG) staining, and transmission electron microscopy (TEM), activity of ALT and AST by enzyme-associated immunosorbent assay as well. Subsequently, mRNAight chain 3 (LC3) toward suppressing HSC autophagy, and PZH exhibited similar effects to that of SM16. Conclusion To conclude, PZH alleviated CCl4-induced liver fibrosis to reduce the production of extracellular collagen and inhibiting the activation of HSC. In addition, their pharmacological mechanisms related to autophagy and TGF-β1/Smad2 signaling pathways were revealed for the first time.Breast cancer has recently been known as the first lethal malignancy in women worldwide. Despite the existing treatments that have improved the patients' prognosis, some types of breast cancer are serious challenges to treat. Therefore, efforts are underway to provide more efficient therapy. Cryptotanshinone (CPT) is a liposoluble diterpenoid derivation of a traditional Chinese herbal medicine called Salvia miltiorrhiza Bunge. It has been considered in the past decades due to its vast therapeutic properties, including anti-tumor, anti-inflammatory, and anti-fibrosis. Recently, studies have found that CPT showed a significant anti-breast cancer effect in vivo and in vitro through different physiological and immunological mechanisms. This study summarized the latest research findings on the antitumor effect of CPT in breast cancer. GDC-0973 MEK inhibitor Further, the main molecular mechanisms based on breast cancer types and combination with other drugs were reviewed to provide essential evidence for future longitudinal research and its clinical application in breast cancer treatment.Neuropsychiatric diseases are a group of disorders that cause significant morbidity and disability. The symptoms of psychiatric disorders include anxiety, depression, eating disorders, autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, and conduct disorder. Various medicinal plants are frequently used as therapeutics in traditional medicine in different parts of the world. Nowadays, using medicinal plants as an alternative medication has been considered due to their biological safety. Despite the wide range of medications, many patients are unable to tolerate the side effects and eventually lose their response. By considering the therapeutic advantages of medicinal plants in the case of side effects, patients may prefer to use them instead of chemical drugs. Today, the use of medicinal plants in traditional medicine is diverse and increasing, and these plants are a precious heritage for humanity. Investigation about traditional medicine continues, and several studies have indicated thecines compared to FDA-approved medicines for the treatment of mental disorders. Therefore, future clinical studies are needed to accelerate the potential use of natural compounds in the management of these diseases.Ophiopogon japonicus (OJ) is a traditional Chinese herbal medicine that has been used for thousands of years. Recently, the anticancer effects of OJ have been reported in multiple types of cancer, particularly in lung cancer. However, the underlying mechanisms remain unclear. In present study, the effects of OJ against NCI-H1299 human lung cancer cells were investigated, and the underlying mechanisms were explored using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS)-based cell metabolomics. As a result, OJ inhibited the proliferation, induced the apoptosis and suppressed the migration of NCI-H1299 cells. A total of 22 differential metabolites responsible for the effects of OJ were screened and annotated based on the LC-MS-based cell metabolomics approach. The altered metabolites were involved in three metabolic pathways, including glycerophospholipid metabolism, ether lipid metabolism and glutathione metabolism. These results showed that cell metabolomics-based strategies are promising tools to discover the action mechanisms of OJ against lung cancer cells.Females have higher inflammatory tolerance because they have some special sex-related anti-inflammatory pathways. Andrographolide, a diterpene lactone compound from Andrographis paniculata (Burm.f.) Nees, has a powerful anti-inflammatory effect. But whether andrographolide regulates sex-related anti-inflammatory pathways in females has yet to be reported. A non-targeted metabonomics method was employed to investigate the metabolic pathways of andrographolide in LPS-induced inflammatory female rats. Substances and genes were then selected out of gender-related pathways discovered by metabonomics experiments and their quantities or expressions were evaluated. Furthermore, the effects of andrographolide on these chemicals or genes in non-inflammatory female rats were also examined in order to investigate the cascade interaction between anti-inflammatory mechanisms and metabolites. The biomarkers of 24 metabolites in plasma were identified. Following pathway enrichment analysis, these metabolic markers were clustthways, andrographolide prevented the stimulation of inflammatory factors on the production of sex hormones. It does not, however, directly inhibit or enhance the synthesis of sex hormones.Higenamine (HG) is a chemical compound found in various plants, such as aconite. Recent pharmacological studies have demonstrated its effectiveness in the management of many diseases. Several mechanisms of action of HG have been proposed; however, they have not yet been classified. This review summarises the signalling pathways and pharmacological targets of HG, focusing on its potential as a naturally extracted drug. Articles related to the pharmacological effects, signalling pathways and pharmacological targets of HG were selected by searching the keyword "Higenamine" in the PubMed, Web of Science and Google Scholar databases without limiting the search by publication years. HG possesses anti-oxidant, anti-apoptotic, anti-inflammatory, electrophysiology regulatory, anti-fibrotic and lipid-lowering activities. It is a structural analogue of catecholamines and possesses characteristics similar to those of adrenergic receptor ligands. It can modulate multiple targets, including anti-inflammation- and anti-apoptosis-related targets and some transcription factors, which directly or indirectly influence the disease course. Other naturally occurring compounds, such as cucurbitacin B (Cu B) and 6-gingerol (6-GR), can be combined with HG to enhance its anti-apoptotic activity. Although significant research progress has been made, follow-up pharmacological studies are required to determine the exact mechanism of action, new signalling pathways and targets of HG and the effects of using it in combination with other drugs.Selective serotonin reuptake inhibitors (SSRIs) are widely used for a variety of diseases, and their impact on semen quality is unclear. We performed a systematic search in PubMed and Embase, and after a strict screening, we included 4 studies with a total of 222 male participants. In result, SSRIs reduced normal sperm morphology (95% CI [-16.29, -3.77], p = 0.002), sperm concentration (95%CI [-43.88, -4.18], p = 0.02), sperm motility (95%CI [-23.46, -0.47], p = 0.04) and sperm DNA fragmentation index (DFI) (95% CI [6.66,21.93], p = 0.0002), without a statistically significant effect on semen volume (95%CI [-0.75,0.65], p = 0.89). Moreover, the impact on both sperm morphology and sperm concentration were observed within the 3-month period of SSRIs use. In general, our meta-analysis showed that SSRIs have a negative effect on semen quality. More larger, randomized, well-controlled clinical studies should be conducted to support our conclusion.
Homepage: https://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html
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