Pharmacology最新文献

Wedelolactone (WED) is a polyphenolic compound with a coumarin skeleton isolated from marigold. Despite its wide application in traditional medicine, its mechanisms of action and safety profile require further investigation. The innovation of this review lies in: (1) the first systematic integration of WED's multi-target mechanisms across diseases through the AMPK/NF-κB/NLRP3 network; (2) clarification of its dose-effect relationship (effective therapeutic window: 5-100 mg/kg) and toxicity thresholds; (3) proposal of clinical translation strategies, including nanodelivery systems to address bioavailability issues . Recent studies revealed novel mechanisms such as WED's inhibition of ferroptosis via GPX4 and modulation of the FXR-bile acid axis , demonstrating efficacy in acute lung injury and liver fibrosis. This article provides a comprehensive framework integrating mechanistic insights and translational research for WED's clinical development.

Background: Escitalopram oxalate (ESC) was extensively reported to improve insomnia in patients with depression/anxiety. The serotonin transporter gene (SLC6A4) was involved in regulating insomnia. However, it is still unclear whether ESC improves insomnia by regulating SLC6A4 expression. Therefore, this study aims to investigate whether ESC improves insomnia by regulating SLC6A4 based on clinical and animal experiments.

Methods: The clinical and animal experiments were involved in this study. For clinical experiments, after all 110 participants were divided into four groups, the portable sleep electroencephalogram monitor, HAMA14 scale, and HAMD24 scale were used to evaluate patients' sleep quality, anxiety, and depression. For animal experiments, after all 18 ICR male mice were randomly divided into three groups (n = 6), the sodium pentobarbital-induced sleeping test, locomotor activity test, elevated plus maze, and open field test were used to evaluate mice's sleep quality and anxiety- and depression-like behaviors. The H&E staining was used to determine pathological injuries in mice's hippocampal tissues. The ELISA kits were adopted to detect the 5-HT, NE, GABA, and Glu levels in the hypothalamus tissue and the CRH, ACTH, and CORT levels in the serum. The PubChem, DrugBank, and Therapeutic Target Database were employed to predict the potential targets of ESC. The IHC staining and Western blot were applied to assay the SLC6A4, 5-HTR1A, and 5-HTR2A expression levels in the hippocampal tissues of mice.

Results: ESC shortened the sleep latency, extended the sleep time, enhanced the sleep efficiency, and improved anxiety and depression in patients and mice. ESC mitigated the pathological injuries in mice's hippocampal tissues. ESC effectively regulated mice's neurotransmitter levels and HPA axis homeostasis, including up-regulating 5-HT and GABA, and down-regulating NE, Glu, CRH, ACTH, and CORT. Moreover, SLC6A4 was predicted as the potential target of ESC. ESC prominently inhibited SLC6A4 expression (P < 0.001) and regulated 5-HTR1A and 5-HTR2A expression (P < 0.001) in hippocampal tissues.

Conclusion: Taken together, ESC was suitable for treating insomnia in the clinic and improved insomnia by targeting SLC6A4 to regulate the HPA axis in mice.

Background: Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies beyond conventional treatments. The increasing interest in natural and synthetic antiproliferative compounds is driven by their ability to target oncogenic pathways implicated in tumor progression, metastasis, and drug resistance. This review explores the potential of bioactive phytochemicals and molecularly targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors, in modulating cancer cell survival, proliferation, and immune evasion. A central focus is placed on the phosphoinositide 3-kinases (PI3Ks)/protein kinase B (AKT), JAK/STAT, and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways, which are frequently dysregulated in therapy-resistant cancers, particularly head and neck cancer.

Summary: Emerging evidence suggests that phytochemicals such as curcumin, resveratrol, and flavonoids not only suppress oncogenic signaling but also enhance apoptosis, inhibit epithelial-mesenchymal transition, and regulate oxidative stress responses. Additionally, recent preclinical and clinical studies indicate that combinatorial applications of phytochemicals with targeted agents can sensitize resistant tumors to chemotherapy and immunotherapy, thereby improving therapeutic efficacy. However, a major challenge limiting the clinical translation of phytochemicals is their low bioavailability and rapid metabolism. Advances in nanoparticle-based drug delivery, synthetic derivatives, and CRISPR-mediated genome editing offer promising solutions to overcome these limitations, ensuring optimal stability, targeted delivery, and enhanced anticancer activity.

Key messages: By integrating traditional phytotherapy with modern molecular oncology, this review highlights novel synergistic strategies that may revolutionize cancer treatment, paving the way for personalized anticancer therapeutics. DBCs and herbal medicine influence key oncogenic pathways, including EGFR, PI3K/AKT, and MEK/ERK. Human papillomavirus (HPV)-positive and HPV-negative tumors exhibit distinct molecular profiles, affecting their response to conventional treatments and adjunctive therapies. Polyphenols such as curcumin, resveratrol, and quercetin, along with herbal extracts including Scutellaria baicalensis and Camellia sinensis, demonstrate the ability to modulate oxidative stress, apoptosis, and immune responses while reducing therapy resistance. Nanoparticle-based formulations improve the bioavailability of these compounds, enhancing their anticancer effects. However, their effectiveness varies based on the HPV status of the tumor, with HPV-positive cancers showing greater sensitivity to immune-modulating compounds.

Introduction: Proton-pump inhibitor (PPI) monotherapy is standard for artificial ulcer healing after gastric endoscopic submucosal dissection, but evidence on the efficacy of PPI combined with gastric mucosal protectants remains inconclusive. This network meta-analysis aimed to compare the efficacy of 10 mucosal protectants combined with PPIs.

Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until January 2025. Included were 20 randomized controlled trials (n = 2,000) comparing PPI monotherapy versus PPI combined with protectants (e.g., rebamipide, ecabet, polaprezinc) or active controls. Primary outcomes included ulcer area reduction, healing rates (4/8 weeks), longest ulcer diameter, and bleeding risk. Frequentist random-effects models synthesized risk ratios (RRs) and MDs with 95% CIs. Consistency was evaluated using design-by-treatment interaction and node splitting. Risk of bias (RoB 2.0) was assessed at the outcome level. Certainty of evidence was graded with GRADE.

Results: Bismuth subcitrate-magnesium granules (BMG) + PPI most effectively reduced 4-week ulcer area (MD: -62.50 mm2, 95% CI: -87.25 to -37.75 vs. PPI; SUCRA = 94%). Ecabet sodium (EB) + PPI achieved the highest 8-week healing rate (RR: 7.71, 95% CI: 5.52-9.91). Hydrotalcite (HT) + PPI best reduced ulcer diameter (MD: -1.87 mm), while teprenone (TN) + PPI optimally prevented bleeding (RR: -3.41, 95% CI: -5.43 to -1.38). Rebamipide + PPI showed efficacy heterogeneity, particularly in large ulcers (>40 mm).

Conclusions: PPI-based combinations likely accelerate healing versus PPI alone, but conclusions are hypothesis generating given indirect evidence and regional concentration of trials. Combination therapy outperforms PPI monotherapy. BMG + PPI is optimal for early ulcer healing, EB + PPI for long-term healing, HT + PPI for diameter reduction, and TN + PPI for bleeding prevention. Stratified regimens by ulcer characteristics are recommended.

Introduction: The administration of medication through feeding tubes (FTs) represents a critical aspect of routine nursing practice. Although guidelines recommend the separate administration of medications to minimize potential interactions, it is common practice in the clinical settings for medications to be combined and administered simultaneously. Since there is a lack of data on this topic, this study assesses the stability of drugs crushed and mixed in water solution concurrently for administration through FT.

Methods: The drug compatibility was evaluated in vitro by monitoring the changes in drug content in water solution over time and identifying potential degradation products using a high-performance liquid chromatography system.

Results: The majority of drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process. The only medication that showed degradation over time was pantoprazole (especially when combined with acetylsalicylic acid and clopidogrel), which was attributed to the acidic environment. The remaining drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process.

Conclusion: This study proves that most drugs can be prepared and administered simultaneously, with the exception of acid-labile drugs, which undergo significant degradation in acidic solutions.

Introduction: High-risk neuroblastoma is a difficult-to-treat cancer with high rates of recurrence and treatment resistance, likely driven by a population of cancer stem cells. Multiple previous studies have suggested that the use of mevalonate pathway inhibitors, such as statins and bisphosphonates, may have anticancer activity against high-risk tumors.

Methods: We aimed to observe the use of mevalonate pathway inhibitors against the cancer stem cell population of high-risk neuroblastoma cell lines SH-SY5Y, SK-N-AS, and SK-N-BE(2)-C using spheroid-based assays.

Results: We observed significant reductions in spheroid formation capability, stem cell frequency, and stemness properties of these neuroblastoma cancer stem cells with fluvastatin and zoledronate treatment.

Conclusion: Treatment with mevalonate pathway inhibitors leads to reduced neuroblastoma cancer stem cell function through reductions in protein geranylgeranylation.

The article "Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway" [Pharmacology. 2017;99(3-4):188-195. https://doi.org/10.1159/000452340] by Lijuan Ding, Shudong Wang, Weiyao Wang, Peng Lv, Donghai Zhao, Feier Chen, Tianjiao Meng, Lihua Dong and Ling Qi has been retracted by the Publisher and the Editor.After the publication of this article, concerns were raised about the integrity of some of the data presented. Specifically, similar features appear between the two panels "FITC-A 740 Y-P" and "FITC-A Mixed" in Figure 3b of the article. In addition, panels in Figure 3b of this article are the same as panels in Figure 3 of another article by different authors, published subsequently in a different journal [1], specifically:Figure 3b panel "FITC-A Tan IIA" is the same as Figure 3c of [1].Figure 3b panel "FITC-A 740 Y-P" is the same as Figure 3a of [1].Figure 3b panel "FITC-A Mixed" is the same as Figure 3b of [1].The authors did not respond to requests to comment on the concerns and provide the raw data within the given timeframe despite multiple attempts of contact. We contacted the authors' institution to request an investigation. However, we did not receive a response. Given the severity of the concerns raised, this article is being retracted. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact.

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and the liver is its main site of distant metastasis. Colorectal cancer liver metastasis (CRLM) is a major cause of CRC-related death. Current treatments, including surgery, chemotherapy, and immunotherapy, have limited efficacy and often cause substantial side effects.

Summary: This review examines the emerging role of traditional Chinese medicine (TCM) in managing CRLM, focusing on its ability to modulate the tumor microenvironment (TME) by inhibiting epithelial-mesenchymal transition, suppressing angiogenesis, and reversing immune evasion. TCM provides a holistic, multi-targeted approach, but most supporting evidence comes from preclinical studies in cell and animal models, with limited clinical validation.

Key messages: TCM shows promise for targeting the CRLM-related TME. Most evidence is preclinical; well-designed clinical trials are urgently needed. Standardization, pharmacokinetics, and regulatory issues remain major barriers to clinical application.

Objective: This study aimed to unveil the impact of optimal pulse technology (OPT) combined with tobramycin and dexamethasone eye ointment on the ocular surface disease index (OSDI) and related outcomes in patients with blepharokeratoconjunctivitis (BKC).

Methods: Ninety-six BKC patients treated at our hospital from September 2022 to September 2023 were divided into a control group (n = 48) and an observation group (n = 48) by a random number table. Both groups received fluorometholone and sodium hyaluronate eye drops. The control group additionally applied tobramycin and dexamethasone eye ointment to the lid margin twice daily, while the observation group underwent OPT on this basis. The clinical efficacy and safety, OSDI, conjunctival hyperemia score, lid margin alteration score, meibomian gland yield secretory score (MGYSS), Demodex mite count, and tear break-up time (TBUT) were compared between the two groups before treatment and at 4 and 8 weeks post-treatment. Additionally, the National Eye Institute Visual Function Questionnaire-25 (NEIVFQ-25) scores were assessed before and after treatment.

Results: The total effective rate in the observation group was 100.00% (48/48) at 8 weeks post-treatment, higher than 89.58% (43/48) in the control group (P < 0.05). The OSDI, conjunctival hyperemia score, lid margin alteration scores, MGYSS, and Demodex mite count all decreased in both groups at 4 and 8 weeks post-treatment compared to baseline, with greater improvements in the observation group(P < 0.05). TBUT and NEIVFQ-25 scores increased in both groups at 8 weeks post-treatment compared to baseline, with the observation group achieving better outcomes than the control group (P < 0.05).

Conclusion: The addition of OPT to standard therapy for BKC is safe and provides superior short-term efficacy. It can alleviate lid margin inflammation, improve ocular surface symptoms, and enhance visual-related quality of life.

Introduction: Alpha-linolenic acid (ALA) is a well-known n-3 polyunsaturated fatty acid. Our previous study showed that ALA inhibits coronary contractions induced by U46619 (a thromboxane A₂ analog) and prostaglandin F_2α (PGF_2α) in pigs by antagonizing prostanoid TP receptors. In this study, we investigated the inhibitory effects of ALA on pig basilar artery contractions and explored the underlying mechanisms.

Methods: The effects of ALA on contractions of pig basilar arteries were assessed. The effects of K+ channel inhibitors on ALA-mediated attenuation were also evaluated.

Results: ALA inhibited TP receptor-mediated contractions induced by U46619 and PGF_2α in a concentration-dependent manner. It shifted the U46619 concentration-response curve to the right and reduced the maximal contraction. The slope of the regression line in the Schild plot analysis exceeded unity, although the difference was not statistically significant. ALA also inhibited PGF_2α-induced contractions (in the presence of SQ 29,548, a TP receptor antagonist) and endothelin-1-induced contractions, without affecting those induced by high-KCl. Among the tested K+ channel inhibitors, Ba2+, an inhibitor of inwardly rectifying K+ (K_ir) channels, most potently attenuated ALA's inhibitory effect on PGF_2α-induced contractions in the presence of SQ 29,548.

Conclusion: These findings indicate that ALA potently inhibits contractions induced by potentially spasmogenic substances in the pig cerebral artery. The inhibitory mechanisms likely involve both antagonism of prostanoid TP receptors and activation of K_ir channels.