Safety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect study.

Purpose: Oroxylin A (OA) is a flavonoid, obtained from the root of Scutellaria baicalensis Georgi which is a traditional Chinese herbal, with antitumor and other pharmacological activities. OA tablets are an innovative drug, and a formal single ascending and multiple dose pharmacokinetic (PK) trial was conducted in humans to evaluate the required to determine the safety and tolerability of OA as well as the effect of food on its PK parameters profile.

Methods: This clinical study consisted of three parts: single ascending dose (400[n = 3], 800, 1600 and 2400 mg OA [n = 8/group] and placebo [n = 6]), multiple dose (1600 or 2400 mg OA [n = 8 / group] and placebo [n = 4] once daily), and food effects (1600 mg OA single dose [n = 12]).

Dual-pathway targeted therapy for Parkinson's disease: Biomimetic nanosomes inhibit ferroptosis and pyroptosis through NLRP3 inflammasome regulation.

Parkinson's disease (PD), a progressive neurodegenerative disorder, is marked by the degeneration of dopaminergic neurons. Emerging evidence highlights the critical involvement of neuronal ferroptosis and microglial pyroptosis in PD pathogenesis. In this study, we first characterized systemic inflammatory alterations in the peripheral blood of PD patients compared to healthy controls, revealing distinct pro-inflammatory signatures.

Psychometric properties of the Mandarin Chinese version of the thin ideal internalization assessment among young Chinese women.

The internalization of the thin ideal is closely associated with body image and eating disturbances among young Chinese women. This study aimed to examine the psychometric properties of a Chinese adaptation of the Thin Ideal Internalization Assessment (C-THIINA). Given that the original THIINA (Kidd et al.

Effect of urolithin A on intracellular survival of by regulating AKT-FOXO1-mediated autophagy.

Tuberculosis (TB), resulting from (Mtb), is one of the leading causes of morbidity and mortality in humans worldwide. Host-directed therapy (HDT) is a novel approach for treating TB, particularly those with drug resistance. Urolithin A (UroA) produced through bioconversion of plant-derived ellagic acid by gut microbes has been proven to have multiple beneficial effects in a variety of diseases without showing undesired adverse reactions.

Discovery of Highly Potent AKR1C3 Inhibitors Treating Sorafenib-Resistant Hepatocellular Carcinoma.

Aldo-keto reductase 1C3 (AKR1C3) plays a key role in tumor progression and chemotherapy resistance, particularly in sorafenib-resistant hepatocellular carcinoma (HCC). Targeting AKR1C3 represents a promising strategy to restore chemosensitivity in resistant HCC. Previous research identified the lead compound through a cascade virtual screening approach (AKR1C3 IC = 130 ± 30 nM, SI (selective index) > 77).

Discovery of highly potent AKR1Cs pan-inhibitors as chemotherapeutic potentiators to restore breast cancer drug resistance.

The acquired resistance of doxorubicin (DOX) significantly limits their application in breast cancer treatment. In earlier investigations, a pan-inhibitor, S07-2010, exhibiting inhibitory activity against Aldo-Keto Reductase 1C1-1C4 (AKR1C1-1C4) was discovered through virtual screening. In this study, four rounds of structural modifications were conducted, and the optimized compound 29 exhibited potent inhibitory activity against AKR1C1-1C4 (AKR1C1 IC = 0.

TA-V Nanozymes with Acid Resistance Capabilities Effectively Target and Alleviate Ulcerative Colitis Lesions via Oral Delivery.

As one of the most common inflammatory bowel diseases (IBDs), ulcerative colitis (UC) has become a rising global health issue that affects people's quality of life. Conventional therapeutic drugs have low bioavailability and may cause serious side effects due to their lack of acidic resistance and lesion-targeting capabilities. The development of novel nanomedicines to overcome these problems is urgently needed.

Self-objectification and depressive symptoms among young Chinese women: The roles of appearance comparison on social networking sites and regulatory emotional self-efficacy.

The present study examined the relationship between self-objectification and depressive symptoms among young Chinese women ( = 324), and investigated the roles of appearance comparison on social networking sites (SNS) and regulatory emotional self-efficacy in this relationship. The results showed that self-objectification was associated with depressive symptoms, and the relationship was mediated by appearance comparison on SNS. The study also found that regulatory emotional self-efficacy moderated the indirect relationship between self-objectification and depressive symptoms via appearance comparison on SNS.

Troglitazone Reduction of Intracellular Mycobacterium tuberculosis Survival Via Macrophage Autophagy Through LKB1-AMPKα Signaling.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb), results in significant disease and death worldwide. Host-directed therapy, including conventional drugs, is a promising antituberculosis strategy that shows synergistic antibacterial effects when combined with antituberculosis drugs. Here, the mycobactericidal effect of 3 antidiabetic drugs was examined.

LW-213, a derivative of wogonin, triggers reticulophagy-mediated cell death in NSCLC via lysosomal damage combined with NPC1 inhibition.

Background: Maintaining intracellular equilibrium is essential for the viability of tumor cells, which tend to be particularly vulnerable to environmental stressors. Consequently, targeting the disruption of this homeostasis offers a promising approach for oncological treatments. LW-213, a novel derivative of wogonin, effectively induces apoptosis in cancer cells by initiating endoplasmic reticulum (ER) stress, although the precise molecular pathways involved remain intricate and multifaceted.

GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition.

Objectives: GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism.

Methods: The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC).

Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production.

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation.

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

Background: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.

Methods: MPTP was introduced into C57BL/6 male mice to generate a PD model.

Paclitaxel combined with Compound K inducing pyroptosis of non-small cell lung cancer cells by regulating Treg/Th17 balance.

Background: Immune checkpoint inhibitors, which have attracted much attention in recent years, have achieved good efficacy, but their use is limited by the high incidence of acquired drug resistance. Therefore, there is an urgent need to develop new immunotherapy drugs. Compound taxus chinensis capsule (CTC) is an oral paclitaxel compound drug, clinical results showed it can change the number of regulatory T cells and T helper cell 17 in peripheral blood.

Pharmacokinetics, tissue distribution, and excretion study of GL-V9 and its glucuronide metabolite 5-O-glucuronide GL-V9 in Sprague-Dawley rats.

The objective of this study is to explore the pharmacokinetics, tissue distribution, and excretion patterns of GL-V9 and its glucuronide metabolite, 5-O-glucuronide GL-V9, following the administration of GL-V9 to Sprague-Dawley (SD) rats. In this research, we developed and validated rapid, sensitive, and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for quantifying GL-V9 and 5-O-glucuronide GL-V9 in various biological samples, including SD rat plasma, tissue homogenate, bile, urine, and feces. Quantification of GL-V9 and 5-O-glucuronide GL-V9 in plasma, tissue homogenate, bile, urine, and feces was performed using the validated LC-MS/MS methods.

Salivary microbiome profiles for different clinical phenotypes of pituitary adenomas by single-molecular long-read sequencing.

The gut and salivary microbiomes have been widely reported to be significantly associated with a number of neurological disorders. The stability of the microbiome in the oral cavity makes it a potentially ideal sample that can be conveniently obtained for the investigation of microbiome-based pathogenesis in diseases. In the present study, we used a single-molecule long-read sequencing technique to study the distribution of the salivary microbiota in patients with pituitary adenoma (PA) and healthy individuals, as well as among four clinical phenotypes of PA.

Oroxylin a promoted apoptotic extracellular vesicles transfer of glycolytic kinases to remodel immune microenvironment in hepatocellular carcinoma model.

Although oroxylin A, a natural flavonoid compound, suppressed progression of hepatocellular carcinoma, whether the tumor microenvironment especially the communication between cancer cells and immune cells was under its modulation remained obscure. Here we investigated the effect of extracellular vesicles from cancer cells elicited by oroxylin A on macrophages in vitro. The data shows oroxylin A elicits apoptosis-related extracellular vesicles through caspase-3-mediated activation of ROCK1in HCC cells, which regulates M1-like polarization of macrophage.

Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy.

Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity. Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer.

Development of Biaryl-Containing Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors for Reversing AKR1C3-Mediated Drug Resistance in Cancer Treatment.

Aldo-keto reductase 1C3 (AKR1C3) is correlated with tumor development and chemotherapy resistance. The catalytic activity of the enzyme has been recognized as one of the important factors in inducing anthracycline (ANT) resistance in cancer cells. Inhibition of AKR1C3 activity may provide a promising approach to restore the chemosensitivity of ANT-resistant cancers.

Trace quantification of GL-V9 and its glucuronide metabolites (5-O-glucuronide GL-V9) in Beagle dog plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

GL-V9, a new synthetic flavonoid derived from wogonin, has shown beneficial biological functions. In this study, accurate and sensitive UPLC-MS/MS methods were developed and validated for the quantification of GL-V9 and its glucuronide metabolite (5-O-glucuronide GL-V9) in Beagle dog plasma. The chromatographic separation was performed on a C8 column (ACE Excel 5 C8 50×3.

AFP deletion leads to anti-tumorigenic but pro-metastatic roles in liver cancers with concomitant CTNNB1 mutations.

HCC remains one of the most prevalent and deadliest cancers. Serum AFP level is a biomarker for clinical diagnosis of HCC, instead the contribution of AFP to HCC development is clearly highly complex. Here, we discussed the effect of AFP deletion in the tumorigenesis and progression of HCC.

Targeting lysosomal HSP70 induces acid sphingomyelinase-mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies.

Background: T cell malignancies proliferate vigorously, are highly dependent on lysosomal function, with limited therapeutic options. Deregulation of lysosomal structure and function has been confirmed to be a key role in the treatment of hematologic malignant disease.

Methods: Cell counting kit 8 and Annexin V/PI staining were used to assess the cell viability and apoptosis rate.

Multiple characteristic alterations and available therapeutic strategies of cellular senescence.

Given its state of stable proliferative inhibition, cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis. Cells undergoing senescence are often associated with the alteration of a series of specific features and functions, such as metabolic shifts, stemness induction, and microenvironment remodeling. However, recent research has revealed more complexity associated with senescence, including adverse effects on both physiological and pathological processes.

Development of highly potent and specific AKR1C3 inhibitors to restore the chemosensitivity of drug-resistant breast cancer.

Aldo-keto reductase 1C3 (AKR1C3) is overexpressed in multiple hormone related cancers, such as breast and prostate cancer, and is correlated with tumor development and aggressiveness. As a phase I biotransformation enzyme, AKR1C3 catalyzes the metabolic processes that lead to resistance to anthracyclines, the "gold standard" for breast cancer treatment. Novel approaches to restore the chemotherapy sensitivity of breast cancer are urgently required.