Effect of connective tissue growth factor and inflammatory factors on the condition and prognosis of patients undergoing reperfusion for acute ischemic stroke.

Objective: To evaluate the impact of connective tissue growth factor (CTGF) and inflammatory factors on the condition and prognosis of patients undergoing reperfusion therapy for acute ischemic stroke (AIS).

Methods: A retrospective analysis was conducted on 212 AIS patients who received reperfusion therapy at Wu Xi Traditional Chinese Medicine Hospital, Suqian Hospital of Traditional Chinese Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2021 to January 2024. Patients were divided into a control group (modified Rankin Scale [mRS] score = 0-3, n = 132) and a study group (mRS score = 4-6, n = 80).

Loss of AXIN1 regulates response to lenvatinib through a WNT/KDM5B/p15 signalling axis in hepatocellular carcinoma.

Background And Purpose: As a highly heterogeneous cancer, hepatocellular carcinoma (HCC) shows different response rates to the multi-kinase inhibitor lenvatinib. Thus, it is important to explore genetic biomarkers for precision lenvatinib therapy in HCC.

Experimental Approach: The effect and mechanism of AXIN1 mutation on HCC were revealed by cell proliferation assay, long-term clone formation assay, sphere formation assay and small molecule inhibitor library screening.

ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway.

Objective: is a traditional Chinese medicinal and functional food with various effects such as anti-liver injury, hypoglycemia, antioxidants, and anti-tumor. The aim of this study was to investigate the protective effects and mechanisms of the ethanolic extract of (EEIB) on alcohol-induced liver injury in mice.

Methods: Fifty-six female C57BL/6 mice were randomly divided into seven groups: control group (Con), ethanol feeding model group (EtOH), Silibinin positive treatment group (EtOH + Silibinin 100 mg/kg), EEIB treatment group (EtOH + EEIB 100, 200, and 400 mg/kg), and EEIB control group (EEIB 400 mg/kg).

Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR Mutant Non-Small Cell Lung Cancer.

Mutant epidermal growth factor receptor (EGFR) is a common driver of non-small cell lung cancer (NSCLC). While mutant EGFR has been reported to limit the efficacy of immunotherapy, a subset of EGFR mutant NSCLC patients benefit from treatment with immune checkpoint inhibitors. A better understanding of how co-occurring genomic alterations in oncogenic driver genes impact immunotherapy efficacy may provide a more complete understanding of cancer heterogeneity and identify biomarkers of response.

Synthesis of 1-Substituted Bicyclo[2.1.1]hexan-2-ones via a Sequential SmI-Mediated Pinacol Coupling and Acid-Catalyzed Pinacol Rearrangement Reaction.

A two-step procedure, combining a SmI-mediated transannular pinacol coupling reaction with an acid-catalyzed pinacol rearrangement process, was employed to prepare a diverse range of 1-substituted bicyclo[2.1.1]hexan-5-ones from cyclobutanedione derivatives.

Improvement effect and mechanism of XuanFuDaiZhe tang on rats with diarrheal irritable bowel syndrome induced by colorectal dilation.

Ethnopharmacological Relevance: XuanFuDaiZhe Tang (XFDZT) is used in traditional Chinese medicine (TCM) to treat diarrhoea-predominant irritable bowel syndrome (IBS-D). Our laboratory has demonstrated that XFDZT remarkably improves various gastrointestinal motility disorders in animal models. However, previous studies have only focused on one or several protein targets without systematically investigating dynamic changes and protein interrelations.

Pseudoginsenoside-F11 reduces cognitive impairment and white matter injury in vascular dementia by alleviating autophagy-lysosomal pathway deficiency.

Background: Vascular dementia (VaD) resulting from chronic cerebral hypoperfusion (CCH) induces cognitive impairment and white matter injury (WMI). We previously found that CCH induces dysfunction of the autophagy-lysosomal pathway (ALP) in white matter (WM) of rats. Enhancing oligodendrocyte autophagy to counteract ALP deficiency is beneficial for cognitive recovery.

KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer.

Background: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrL activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.

PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear.

ALKBH5 regulates paclitaxel resistance in NSCLC via inhibiting CEMIP-mediated EMT.

N6-methyladenosine (m6A) is the most prevalent mRNA modification, and it is verified to be closely correlated with cancer occurrence and progression. The m6A demethylase ALKBH5 (alkB homolog 5) is dysregulated in various cancers. However, the role and underlying mechanism of ALKBH5 in the pathogenesis and especially the chemo-resistance of non-small cell lung cancer (NSCLC) is poorly elucidated.

Metabolomics Reveals Molecular Signatures for Psoriasis Biomarkers and Drug Targets Discovery.

Purpose: Psoriasis is a chronic, multi-system skin disease that can be influenced by immunological, environmental, and genetic factors. Plasma metabolomic analysis can provide a great deal of information on potential diagnostic biomarkers, pathogenesis and personalized treatment. However, the role of metabolites in psoriasis is unknown.

Gain-of-function mutations in the catalytic domain of promote lung cancer malignant phenotypes via the MAPK/ERK signaling pathway.

Lung cancer is a lethal malignancy lacking effective therapies. Emerging evidence suggests that epigenetic enzyme mutations are closely related to the malignant phenotype of lung cancer. Here, we identified a series of gain-of-function mutations in the histone methyltransferase DOT1L.

Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats.

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO.

Phosphorylation of STAT3 at Tyr705 contributes to TFEB-mediated autophagy-lysosomal pathway dysfunction and leads to ischemic injury in rats.

We previously reported that permanent ischemia induces marked dysfunction of the autophagy-lysosomal pathway (ALP) in rats, which is possibly mediated by the transcription factor EB (TFEB). However, it is still unclear whether signal transducer and activator of transcription 3 (STAT3) is responsible for the TFEB-mediated dysfunction of ALP in ischemic stroke. In the present study, we used AAV-mediated genetic knockdown and pharmacological blockade of p-STAT3 to investigate the role of p-STAT3 in regulating TFEB-mediated ALP dysfunction in rats subjected to permanent middle cerebral occlusion (pMCAO).

Discovery of Dual Lysine Methyltransferase G9a and EZH2 Inhibitors with In Vivo Efficacy against Malignant Rhabdoid Tumor.

In recent years, it has been proposed that G9a/EZH2 dual inhibition is a promising cancer treatment strategy. Herein, we present the discovery of G9a/EZH2 dual inhibitors that merge the pharmacophores of G9a and EZH2 inhibitors. Among them, the most promising compound displayed potent inhibitory activities against G9a (IC = 2.

Hyperactive neuronal autophagy depletes BDNF and impairs adult hippocampal neurogenesis in a corticosterone-induced mouse model of depression.

Depression is a mental disorder that poses a serious threat to human health. Adult hippocampal neurogenesis (AHN) is closely associated with the efficacy of antidepressants. Chronic treatment with corticosterone (CORT), a well-validated pharmacological stressor, induces depressive-like behaviors and suppresses AHN in experimental animals.

Design, synthesis and evaluation of the novel chalcone derivatives with 2,2-dimethylbenzopyran as HIF-1 inhibitors that possess anti-angiogenic potential.

Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis and poor patient prognosis, has been recognized as an important cancer drug target. Up to now, some HIF-1 inhibitors with diverse skeletal structures were reported as anticancer agents, mostly natural product-derived compounds. In this study, we designed and synthesized a series of chalcone-based compounds with 2,2-dimethylbenzopyran using the combination principles to select benzopyrans and chalcones natural products.

TM2, a novel semi-synthetic taxoid, exerts anti-MDR activity in NSCLC by inhibiting P-gp function and stabilizing microtubule polymerization.

Taxane agents are of particular interest in non-small cell lung carcinomas (NSCLC) treatment, while multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) limits their clinical efficacy. TM2, a chemically semi-synthesized taxane derivative, exerted significant anti-cancer efficacy in vitro and in vivo, especially against vincristine-resistant and adriamycin-resistant cancer cells. In this study, the anti-cancer effect of TM2 on drug-resistant NSCLC was evaluated both in vitro and in vivo, and the mechanism underlying its anti-MDR activity was further clarified.

An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer.

Background: Lung cancer is a kind of malignancy with high morbidity and mortality worldwide. Paclitaxel (PTX) is the main treatment for non-small cell lung cancer (NSCLC), and resistance to PTX seriously affects the survival of patients. However, the underlying mechanism and potential reversing strategy need to be further explored.