Inhibitory Effects of Alkaloids on BCRP Implicated in Reversing Multidrug Resistance: A Case Example of Enhancing Temozolomide Cytotoxicity.

Breast cancer resistance protein (BCRP), an important ATP-binding cassette transporter, is mainly responsible for drug efflux from cells, especially in high-expressing tumor cells, and is closely associated with multidrug resistance (MDR). Numerous studies have demonstrated that the inhibition of BCRP can reverse MDR, so inhibiting BCRP is considered to be a promising strategy for cancer treatment. Alkaloids are the primary bioactive ingredients in various traditional Chinese medicines (TCMs), some of which have been reported to reverse MDR by inhibiting BCRP.

Discovery of Novel Isoindolin-1-one Derivatives as GABA Receptors Positive Allosteric Modulators with Antiepileptic Efficacy.

Epilepsy is one of the most common and life-threatening neurological diseases, and the GABARs are important therapeutic targets for epilepsy. Herein, a series of novel 2,7-disubstituted isoindolin-1-one derivatives were designed and synthesized, and extensive structure-activity relationships led to a number of highly potent PAMs of GABARs with EC values at 10-10 M level and value of 5-15-fold. In particular, exhibited strong in vitro potentiation effects toward both synaptic and extra-synaptic GABARs, and produced highly potent in vivo efficacies in mouse seizure models, including sc-PTZ (ED = 8.

Integration of AND logic circuit with CRISPR/Cas12a system for sensitive detection of biomarkers and accurate discrimination of breast cancer cells.

Flap endonuclease 1 (FEN1) is a structure-selective nuclease that is of great significance in maintaining genomic stability. FEN1 is up-regulation in various cancers and is regarded as a new biomarker for cancer diagnosis. Herein, we integrate DNA logic circuit with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system for sensitive detection of FEN1 at the cellular level and accurate discrimination of different cell types.

Apigenin alleviates dextran sulfate sodium-induced ulcerative colitis via regulation of endoplasmic reticulum stress in goblet cells.

Ulcerative colitis (UC) significantly impairs quality of life and incurs substantial economic costs. Apigenin, a flavonoid abundant in fruits and vegetables, has demonstrated potential in UC management. Utilizing DSS-induced UC mouse models and LS 174 T goblet cell models, this study elucidates apigenin's protective mechanisms.

Knowledge and stigma of autism spectrum disorders in Chinese university students in the context of inclusive education.

This study investigated knowledge of autism spectrum disorder and associated stigma among Chinese university students, utilizing the cross-culturally validated Chinese version of the Autism Stigma and Knowledge Questionnaire. A total of 2,081 students from 25 provinces participated in an online survey. Independent-samples t-tests and one-way ANOVAs revealed that female students, upper-grade students, normal-education students, special education majors, and those who had completed inclusive education courses demonstrated significantly higher levels of ASD knowledge and lower levels of stigma.

F-box only protein 10 protects against kidney tubulointerstitial fibrosis by inhibiting ACSL4-mediated lipid peroxidation and ferroptosis.

Renal tubular epithelial cell ferroptosis is significantly linked to kidney tubulointerstitial fibrosis, a critical pathological condition in chronic kidney disease. F-box only protein 10 (FBXO10), a newly identified ferroptosis-regulating gene, plays a role in various pathological contexts; however, its involvement in kidney tubulointerstitial fibrosis is not yet fully understood. This research sought to investigate whether FBXO10 regulates ferroptosis in kidney tubular epithelial cells and its relationship with kidney tubulointerstitial fibrosis in both animal and cellular models.

Apigenin-Mediated ESCRT-III Activation and Mitophagy Alleviate LPS-Induced Necroptosis in Renal Cells.

Apigenin (API) is a flavonoid widely distributed in vegetables and fruits that exhibits numerous biological functions. Lipopolysaccharide (LPS), a key component of the outer membrane of Gram-negative bacteria, can cause kidney injury when released into the bloodstream. Necroptosis is a form of programmed cell death characterized by the rupture of cell membranes.

Luteolin Modulate Endoplasmic Reticulum Stress by Targeting SIRT1 to Ameliorate DSS-Induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities.

Construction of a dual-color fluorescent light-up biosensor based on sequential coding for label-free and sensitive detection of multiple Piwi-interacting RNAs.

We construct a dual-color light-up biosensor for label-free and sensitive detection of multiple piRNAs. This biosensor exhibits high sensitivity with a limit of detection of 3.19 aM for piRNA-36026 and 4.

Effects of music therapy on physiological response and anxiety in perioperative ophthalmic patients: a systematic review.

Purpose: The purpose of this study is to evaluate the effectiveness of music therapy on physiological response and anxiety in perioperative ophthalmic patients. Furthermore, to explore the differentiation of intervention effects based on different intervention timing and music types.

Methods: Five databases including PubMed, Embase, Web of Science, the Cochrane library and CINAHL were adopted for comprehensive search, from the inception of the database to October 2024.

Lighting up three-dimensional nanolantern for circular RNA imaging and precise gene therapy.

Circular RNAs (circRNAs) are a category of endogenous single-stranded RNAs with covalently closed head-to-tail topology, and they play a crucial part in regulating gene expression at post-transcriptional and transcriptional levels. Herein, we construct a three-dimensional nanolantern for circRNA imaging and precise gene therapy. This assay involves an integrated multi-functionalized lantern-shaped probe.

Assessment of genetic diversity in Korean field mouse (Apodemus peninsulae): A study based on microsatellite molecular markers.

Background: Understanding the genetic background of Korean field mouse(Apodemus peninsulae Thomas, 1906) is important for employing the animal as an experimental model in research. However, limited genetic information is available about A. peninsulae.

Inhibitory Effects of Alkaloids on OATP1B1 In Vitro and In Vivo: Prediction for Food/Herb-Drug Interactions and Hepatoprotective Effects Based on Structure-Activity Relationships.

Alkaloids, a class of low-molecular-weight nitrogenous compounds, attract a great deal of interest because of their biological activities and therapeutic potential. Yet, surprisingly little is known about their interactions with drug transporters, especially Organic Anion Transporting Polypeptide 1B1 (OATP1B1), a liver-specific uptake transporter, which is closely associated with drug-induced liver injury (DILI). This study aims to investigate the inhibitory effects of 160 alkaloids on OATP1B1, assess the hepatoprotective effects against bosentan-induced liver injury, and elucidate the structure-activity relationships of alkaloids with OATP1B1.

Apigenin Reduces Lipid Droplet Accumulation in Hepatocytes by Enhancing Chaperone-Mediated Autophagy via AMPK.

Apigenin (4',5,7-trihydroxyflavone) is a significant natural flavonoid compound that is abundantly found in various fruits and vegetables. It has been demonstrated to alleviate nonalcoholic fatty liver disease and exhibit lipid-lowering effects. However, its impact on lipid droplet (LD) degradation in hepatocytes remains unclear.

Inhibitory effects of flavonoids on organic cation transporter 1: Implications for food/herb-drug interactions and hepatoprotective effects.

Organic cation transporter 1 (OCT1, gene symbol: SLC22A1) is mainly responsible for the hepatic uptake of various cationic drugs, closely associated with drug-induced liver injury (DILI). Screening and identifying potent OCT1 inhibitors with little toxicity in natural products is of great value in alleviating OCT1-mediated liver injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions (FDIs).

Discovery of 4-(Arylethynyl)piperidine Derivatives as Potent Nonsaccharide -GlcNAcase Inhibitors for the Treatment of Alzheimer's Disease.

Inhibiting -GlcNAcase and thereby up-regulation of the -GlcNAc levels of tau was a potential approach for discovering AD treatments. Herein, a series of novel highly potent OGA inhibitors embracing a 4-(arylethynyl)piperidine moiety was achieved by capitalizing on the substrate recognition domain. Extensive structure-activity relationships resulted in compound with significant enzymatic inhibition (IC = 4.

Up-regulation of long non-coding RNA H19 ameliorates renal tubulointerstitial fibrosis by reducing lipid deposition and inflammatory response through regulation of the microRNA-130a-3p/long-chain acyl-CoA synthetase 1 axis.

Long non-coding RNA (lncRNA) H19 is an extensively studied lncRNA that is related to numerous pathological changes. Our previous findings have documented that serum lncRNA H19 levels are decreased in patients with chronic kidney disorder and lncRNA H19 reduction is closely correlated with renal tubulointerstitial fibrosis, an essential step in developing end-stage kidney disease. Nonetheless, the precise function and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis are not fully comprehended.

Construction of a Spatial-Confined Self-Stacking Catalytic Circuit for Rapid and Sensitive Imaging of Piwi-Interacting RNA in Living Cells.

Piwi-interacting RNAs (piRNAs) are small noncoding RNAs that repress transposable elements to maintain genome integrity. The canonical catalytic hairpin assembly (CHA) circuit relies on random collisions of free-diffused reactant probes, which substantially slow down reaction efficiency and kinetics. Herein, we demonstrate the construction of a spatial-confined self-stacking catalytic circuit for rapid and sensitive imaging of piRNA in living cells based on intramolecular and intermolecular hybridization-accelerated CHA.

Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb-drug interaction and drug-induced kidney injury.

Multidrug and toxin extrusion protein 1 (MATE1), an efflux transporter mainly expressed in renal proximal tubules, mediates the renal secretion of organic cationic drugs. The inhibition of MATE1 will impair the excretion of drugs into the tubular lumen, leading to the accumulation of nephrotoxic drugs in the kidney and consequently potentiating nephrotoxicity. Screening and identifying potent MATE1 inhibitors can predict or minimize the risk of drug-induced kidney injury.