Entrectinib can induce nerve cell damage by inhibiting PI3K-AKT and TGF-β signaling pathways.

Background: The tyrosine receptor kinase inhibitor (TRKi) entrectinib is used to treat neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors and ROS1-positive patients. Despite its impressive efficacy against cancer, the clinical application is still limited by the central nervous system (CNS)-related toxicities. However, the precise mechanism of such CNS-related toxicities remains elusive.

Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism.

The endoplasmic reticulum (ER) is a crucial cellular organelle involved in protein synthesis, folding, modification, and transport. Exposure to internal and external stressors can induce endoplasmic reticulum stress (ERS), leading to abnormal protein folding and ER malfunction. This stress can disrupt lipid synthesis, metabolism, and transport processes.

Fabrication of soy protein isolate-konjac glucomannan emulsion gels to mimic the texture, rheological behavior and in vitro digestion of pork fat.

Fats are essential nutrients, but excessive intake can lead to obesity and certain cardiovascular diseases. In this study, an emulsion gel was prepared using alkali heat treatment with soy protein isolate (SPI) and konjac glucomannan (KGM) as a fat substitute, while pork fat was used as the control. Gel strength, rheological properties, and water holding capacity of soy protein isolate-konjac glucomannan (SPI-KGM) emulsion gel improved progressively with higher KGM content.

Clinical characteristics and pregnancy outcomes in pregnant women with TB: a retrospective cohort study.

Purpose: The influence of pregnancy on tuberculosis (TB) has not been well studied. This study aimed to investigate the demographics, clinical characteristics and outcomes of pregnant-related TB compared with the general population with TB.

Methods: We retrospectively analysed medical records of women during pregnancy or within six months postpartum with active TB who were admitted to the West China Hospital between 2011 and 2022.

SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma.

The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL).

Pharmacological activities of L. plants and its exploitation and utilization.

The study aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and exploitation and utilizations of L. Besides, the possible tendency and perspective for future research of this plant are discussed, as well. This article uses " L.

Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes based on AMPK signaling pathway.

Background: With the increasing awareness of the safety of traditional Chinese medicine and food, as well as in-depth studies on the pharmacological activity and toxicity of Zanthoxylum armatum DC. (ZADC), it has been found that ZADC is hepatotoxic. However, the toxic substance basis and mechanism of action have not been fully elucidated.

Synthesis and characterization of ion-induced sodium alginate/soy protein isolate microgels for the controlled release.

In this study, sodium alginate/ soy protein isolate (SPI) microgels cross-linked by various divalent cations including Cu, Ba, Ca, and Zn were fabricated. Cryo-scanning electron microscopy observations revealed distinctive structural variations among the microgels. In the context of gastric pH conditions, the degree of shrinkage of the microgels followed the sequence of Ca > Ba > Cu > Zn.

A toxicological review of alkaloids.

Alkaloids are naturally occurring compounds with complex structures found in natural plants. To further improve the understanding of plant alkaloids, this review focuses on the classification, toxicity and mechanisms of action, providing insight into the occurrence of alkaloid-poisoning events and guiding the safe use of alkaloids in food, supplements and clinical applications. Based on their chemical structure, alkaloids can be divided into organic amines, diterpenoids, pyridines, isoquinolines, indoles, pyrrolidines, steroids, imidazoles and purines.

Study on SH-SY5Y autophagy inhibition and apoptosis induced by methanol extract of DC. based on mTOR signal pathway.

Background: Zanthoxylum armatum DC. (ZADC) is a novel food raw material resource, offering both edible and medicinal properties. Recent research has unveiled the toxic nature of ZADC, particularly its close association with the nervous system.

Predicting circRNA-miRNA interactions utilizing transformer-based RNA sequential learning and high-order proximity preserved embedding.

A key regulatory mechanism involves circular RNA (circRNA) acting as a sponge to modulate microRNA (miRNA), and thus, studying their interaction has significant medical implications. In this field, there are currently two pressing issues that remain unresolved. Firstly, due to the scarcity of verified interactions, we require a minimal amount of samples for training.

Behavioral impulse and time pressure jointly influence intentional inhibition: evidence from the Free Two-Choice Oddball task.

Intentional inhibition is a crucial component of self-regulation, yet it is under-researched, because it is difficult to study without external stimuli or overt behaviors. Although Free-Choice tasks have been developed, it remains unclear how two key design features (i.e.

Host factors associated with false negative results in an interferon-γ release assay in adults with active tuberculosis.

Objective: To identify host factors associated with false-negative results of interferon-γ release tests in adults with active tuberculosis.

Methods: The clinical data of 943 patients with active tuberculosis diagnosed by acid-fast smear staining, culture, PCR and pathological examination at West China Hospital of Sichuan University were retrospectively analysed. According to the results of the interferon γ release test (IGRA), the patients were divided into the IGRA group and IGRA group.

SIKs Regulate HDAC7 Stabilization and Cytokine Recall in Late-Stage T Cell Effector Differentiation.

Understanding the mechanisms underlying the acquisition and maintenance of effector function during T cell differentiation is important to unraveling how these processes can be dysregulated in the context of disease and manipulated for therapeutic intervention. In this study, we report the identification of a previously unappreciated regulator of murine T cell differentiation through the evaluation of a previously unreported activity of the kinase inhibitor, BioE-1197. Specifically, we demonstrate that liver kinase B1 (LKB1)-mediated activation of salt-inducible kinases epigenetically regulates cytokine recall potential in effector CD8+ and Th1 cells.

Neurotoxicity study of ethyl acetate extract of Zanthoxylum armatum DC. on SH-SY5Y based on ROS mediated mitochondrial apoptosis pathway.

Ethnopharmacological Relevance: Zanthoxylum armatum DC. (ZADC) is a traditional medicinal plant with various pharmacological activities and is widely used in China, Japan, India, and other regions. Previous studies have revealed that the methanol extract of ZADC can cause neurotoxicity symptoms in rats, such as drooling, decreased appetite, decreased movement, and increased respiratory rate.

The Causal Impact of the Gut Microbiota on Respiratory Tuberculosis Susceptibility.

Introduction: Recent cross-sectional research has demonstrated a substantial link between tuberculosis (TB) and gut microbiota. Nevertheless, the causal impact of the gut microbiota on TB susceptibility in humans remains unknown.

Methods: The Mendelian randomization (MR) method was utilized for investigating the causality between them.

Zanthoxylum armatum DC fruit ethyl acetate extract site induced hepatotoxicity by activating endoplasmic reticulum stress and inhibiting autophagy in BRL-3A models.

Ethnopharmacological Relevance: Zanthoxylum armatum DC (Z. armatum) is renowned not only as a culinary spice but also as a staple in traditional ethnic medicine, predominantly in Southeast Asia and various other regions. Recent research has unveiled its multifaceted pharmacological properties, including anti-inflammatory, antibacterial, and toothache relief effects.

TSC2 S1365A mutation potently regulates CD8+ T cell function and differentiation and improves adoptive cellular cancer therapy.

MTORC1 integrates signaling from the immune microenvironment to regulate T cell activation, differentiation, and function. TSC2 in the tuberous sclerosis complex tightly regulates mTORC1 activation. CD8+ T cells lacking TSC2 have constitutively enhanced mTORC1 activity and generate robust effector T cells; however, sustained mTORC1 activation prevents generation of long-lived memory CD8+ T cells.

The effect of acupuncture on oestrogen receptors in rats with benign prostatic hyperplasia.

The effects of acupuncture on the protein and gene expression of oestrogen receptors (ERs) alpha (α) and beta (β) in testosterone-induced benign prostatic hyperplasia (BPH) in rats remains unclear. In this study, rats were randomly divided into four groups (n = 10 per group). The rats in the blank group did not receive any treatment, while the rats in the model group were injected intraperitoneally with testosterone propionate for 28 days to establish the BPH model and then randomly sub-divided into a control group, an acupuncture group and a finasteride group (positive control group).

Revealing the mechanism of Zanthoxylum armatum DC. extract-induced liver injury in mice based on lipidomics.

Ethnopharmacological Relevance: Zanthoxylum armatum DC. (Z. armatum) is an herbal medicine with various active ingredients and pharmacological effects.

Huannao Yicong decoction ameliorates cognitive deficits in APP/PS1/tau triple transgenic mice by interfering with neurotoxic interaction of Aβ-tau.

Ethnopharmacological Relevance: Huannao Yicong decoction (HYD) has been used in the study of AD for many years, which consists of Polygonum multiflorum Thunb., Panax ginseng C.A.

Serendipitous Discovery of T Cell-Produced KLK1b22 as a Regulator of Systemic Metabolism.

In order to study mechanistic/mammalian target of rapamycin's role in T cell differentiation, we generated mice in which Rheb is selectively deleted in T cells (T-Rheb-/- C57BL/6J background). During these studies, we noted that T-Rheb-/- mice were consistently heavier but had improved glucose tolerance and insulin sensitivity as well as a marked increase in beige fat. Microarray analysis of Rheb-/- T cells revealed a marked increase in expression of kallikrein 1-related peptidase b22 (Klk1b22).

Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts.

Although the biological utilities of endogenous RNAi (endo-RNAi) have been largely elusive, recent studies reveal its critical role in the non-model fruitfly Drosophila simulans to suppress selfish genes, whose unchecked activities can severely impair spermatogenesis. In particular, hairpin RNA (hpRNA) loci generate endo-siRNAs that suppress evolutionary novel, X-linked, meiotic drive loci. The consequences of deleting even a single hpRNA (Nmy) in males are profound, as such individuals are nearly incapable of siring male progeny.