Advancements in CDK-based Dual-target Inhibitors for Cancer Therapy.

Background: The cyclin-dependent kinases (CDKs) play a crucial role in the normal progression of these stages. In tumor cells, CDKs are often highly expressed, leading to uncontrolled cell proliferation. Inhibiting the activity of CDKs in tumor cells can inhibit their growth and proliferation, thereby achieving anti-tumor effects.

Enhancing NK Cell Antitumor Activity With Natural Compounds: Research Advances and Molecular Mechanisms.

In recent years, immunotherapy has become a novel antitumor strategy in addition to traditional surgery, radiotherapy, and chemotherapy and has exhibited promising results in clinical applications. Despite significant breakthroughs in immunotherapy, such as immune checkpoint blockade and CAR-T cell therapy, it remains necessary to develop more efficacious, safer, and cheaper immunotherapeutic drugs due to factors including small reaction populations, acquired resistance, adverse side effects, and high costs. Natural killer (NK) cells are preeminent cytotoxic lymphocytes of the innate immune system that act as the first line of defense against tumors and synergistically enhance the adaptive immune response of T lymphocytes.

Banxia Baizhu Tianma Decoction alleviates pentylenetetrazol-induced epileptic seizures in rats by preventing neuronal cell damage and apoptosis and altering serum and urine metabolic profiles.

Ethnopharmacological Relevance: Epilepsy (EP) is one of the most prevalent chronic neurological disorders in children, characterised by a prolonged course and a propensity for recurrence. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine formula, is commonly employed in the clinical management of EP and has demonstrated satisfactory therapeutic effects.

Aim Of The Study: This study aimed to evaluate the anti-epileptic effects of BBTD and to explore its molecular mechanisms.

PLXNA1 confers enzalutamide resistance in prostate cancer via AKT signaling pathway.

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR).

Mechanism of baicalein in treatment of castration-resistant prostate cancer based on network pharmacology and cell experiments.

Objective: Baicalein, one of the most abundant flavonoids found in Chinese herb Georgi, exhibits pharmacological activities against various cancers. However, the precise pharmacological mechanism of baicalein in treating castration-resistant prostate cancer (CRPC) remains elusive. This study aimed to elucidate the potential mechanism of baicalein against CRPC through a combination of network pharmacology and experimental approaches, thereby providing new avenues for research in CRPC treatment.

Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer.

Background: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins.

The discovery of water-soluble indazole derivatives as potent microtubule polymerization inhibitors.

Taking a previously discovered indazole derivative 1 as a lead, systematic structural modifications were performed with an indazole core at the 1- and 6-positions to improve its aqueous solubility. Among the designed indazole derivatives, 6-methylpyridin-3-yl indazole derivative 8l and 1H-indol-4-yl indazole derivative 8m exhibited high potency in the low nanomolar range against A549, Huh-7, and T24 cancer cells, including Taxol-resistant variant cells (A549/Tax). As a hydrochloride salt, 8l exhibited much improved aqueous solubility, and its log P value fell into a favorable range.

Suppressing NK Cells by Astragaloside IV Protects Against Acute Ischemic Stroke in Mice Inhibiting STAT3.

Natural killer (NK) cells, a key member of innate lymphocytes, are a promising immunotherapeutic target for ischemic stroke. Astragaloside IV (ASIV) is isolated from (Fabaceae), a herbal medicine possessing immunomodulatory ability. This study investigated the effect of ASIV on NK cells during the acute stage of brain ischemic injury in a mouse model of middle cerebral artery occlusion (MCAO).

Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice.

Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD). However, the side effects of OCA may limit its application in clinics. We identified previously that isotschimgine (ITG) is a non-steroidal FXR selective agonist and has potent therapeutic effects on NAFLD in mice.

Astragaloside IV suppresses post-ischemic natural killer cell infiltration and activation in the brain: involvement of histone deacetylase inhibition.

Natural killer (NK) cells, a type of cytotoxic lymphocytes, can infiltrate into ischemic brain and exacerbate neuronal cell death. Astragaloside IV (ASIV) is the major bioactive ingredient of Astragalus membranaceus, a Chinese herbal medicine, and possesses potent immunomodulatory and neuroprotective properties. This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells.

Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia.

Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain.

Buyang Huanwu Decoction Attenuates Infiltration of Natural Killer Cells and Protects Against Ischemic Brain Injury.

Background/aims: Natural killer (NK) cells are among the first immune cells that respond to an ischemic insult in human brains. The infiltrated NK cells damage blood-brain barrier (BBB) and exacerbate brain infarction. Buyang Huanwu Decoction (BHD), a classic Chinese traditional herbal prescription, has long been used for the treatment of ischemic stroke.