Pharmacology最新文献

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: 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.

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.

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: Muscular dystrophy (MD) refers to a group of genetic disorders leading to progressive weakness and degeneration of skeletal muscle. Among them, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most common types. Histone deacetylase inhibitors (i.e., givinostat) is a recently approved therapy for DMD. In this systematic review, we aimed to evaluate givinostat in MD patients regarding safety and efficacy.

Methods: A systematic review was performed according to the PRISMA guidelines by searching through Medline, Embase, Cochrane Library, and Web of Science. Only randomized control trials comparing givinostat vs. placebo or other therapies are included. The primary outcomes were motor function alteration and histopathologic muscle changes and the secondary outcomes were the adverse reactions.

Results: A total of 188 records were identified, and after screening, two clinical trials met the inclusion criteria. In DMD patients, givinostat significantly slowed disease progression, improving four-stair climb times (p = 0.037) and reducing muscle fat infiltration. In BMD patients, fibrosis progression was not significantly different (p = 0.8282), but MRI showed reduced muscle fat replacement. Common adverse events included diarrhoea, thrombocytopenia, and hypertriglyceridemia, leading to dose reductions, though no new safety signals or treatment-related deaths were observed.

Conclusion: Givinostat seems to be effective in slowing disease progression in DMD but has little benefit in BMD. Its safety profile requires rigorous monitoring. Efficacy difference might be explained by the pathophysiology of the disease and the progression rate. Larger and longer follow-up trials are warranted to confirm longer term benefits and to optimize dosing strategies. Givinostat offers potential as a disease-modifying therapy for DMD but requires further investigation to establish its role in BMD.

Background: Sepsis, a severe infectious systemic syndrome with high morbidity and mortality, is pathologically characterized by multi-organ dysfunction, with pulmonary involvement predominating as acute lung injury (ALI) or its severe progression to acute respiratory distress syndrome. Contemporary therapeutic strategies exhibit limited efficacy, while traditional Chinese medicine (TCM) grounded in millennia of clinical empiricism demonstrates unique pharmacological advantages through multi-component and multi-target regulation.

Summary: The mechanism underlying sepsis-induced ALI centers on dysregulated inflammatory response, redox imbalance, and coagulopathy. This review systematically evaluates the effectiveness, mechanism, and clinical research progress of eight TCM formulas in the treatment of sepsis and ALI. Accumulating fundamental research and clinical trials demonstrate the potential of these TCM formulas in treating sepsis-induced ALI. The challenges and opportunities of TCM formulas in treating, including but not limited to, sepsis-induced ALI were emphasized.

Key message: This review bridges traditional therapeutic wisdom with modern pathogenesis understanding, offering novel combinatorial strategies for sepsis-induced ALI management.

Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons, finally leading to death by respiratory failure. However, no effective drug is available for treating patients with ALS owing to the complex pathological mechanisms. Herbal medicines are globally known for the effects of their multiple bioactive components and lack of adverse effects. This study investigated the effects of a combined herbal medicine formulation containing Achyranthes bidentata Blume, Gastrodia elata Blume, and Chaenomeles sinensis Koehne extracts on motor function and to analyze the underlying biological mechanisms in the gastrocnemius and tibia anterior muscles and spinal cord of hSOD1G93A mice.

Methods: Rotarod and footprint analyses were performed to examine motor function. The biological mechanisms were examined using Western blot and immunohistochemistry analyses of the muscles and spinal cord in hSOD1G93A mice.

Results: Herbal medicine treatment improved motor function in hSOD1G93A mice by reducing the expression of inflammation-related proteins (glial fibrillary acidic protein and CD11b) and oxidative stress-related proteins (heme oxygenase 1 and ferritin) in the gastrocnemius and tibia anterior muscles and spinal cord. It also regulated autophagy in the muscles and spinal cord of hSOD1G93A mice.

Conclusion: Collectively, these findings suggest that the herbal medicine formulation reported herein may facilitate management of diseases with complex pathological mechanisms, such as ALS, or those with unclear pathological mechanisms.

Introduction: While the high morbidity of cancer continues to affect the global population, there are currently no effective and safe therapeutic options. Amphotericin-A21 (AmB-A21) is a derivative of amphotericin B (AmB). Its efficacy is similar to that of its precursor, but it has greater safety. AmB-A21 can induce apoptosis in neoplastic cells, meaning it could potentially be employed as a safe chemotherapeutic agent.

Methods: This study examined the antineoplastic effect of AmB-A21 on MCF-7, U-87MG, and A-549 cells by evaluating cytotoxicity, apoptosis, and protein expressions associated with cell death. MCF-7 cells were treated with AmB-A21 at 40 µm, U-87MG cells with AmB-A21 at 423 µm, and A-549 cells with AmB-A21 at 192 µm for all experiments. Non-treated cells were used as negative control. Comparative studies using AmB and cisplatin were also carried out.

Results: AmB-A21 reduced cell viability in a time-dependent manner. At 72 h, cell viability was reduced by 67% in MCF-7, 48% in U-87MG, and 47% in A-549 cells. AmB-A21 induced apoptosis by 50%, 58%, and 80% in MCF-7, U-87MG, and A-549 cells, respectively. A significant reduction in Bcl-2 expression and an important increase in Bax expression (55%/2.8-fold in MCF-7 cells, 40%/3.5 fold in U-87MG cells, and 45%/4.5-fold in A-549 cells) were also observed. AmB-A21 likewise increased caspase 9 activity 8.5-fold in MCF-7 cells, 4.1-fold in U-87MG cells, and 8-fold in A-549 cells.

Conclusion: Although comparatively AmB-A21 concentration for U-87MG cells was higher, it has potential for cancer therapy due to its safer profile.

Introduction: Exposure to potential drug-drug interactions (pDDIs) can be a notable source of avoidable drug-related harm that requires adequate management to prevent medical errors. We aimed to evaluate pDDIs and associated factors in hospitalized urological patients on admission, during hospitalization, and on discharge.

Methods: A retrospective cohort study was conducted at the Clinic of Urology of the University Clinical Centre Kragujevac, Serbia. To detect pDDIs, we used Lexicomp, which categorizes pDDIs as follows: X (avoid combination), D (consider therapy modification), C (monitor therapy), B (no action needed), and A (no known interaction). Multiple linear regression analysis was used to identify factors associated with the number of pDDIs.

Results: More than half of the 220 included patients had at least one pDDI on admission and discharge (57.3% and 63.6%, respectively), whereas 95.0% had at least one pDDI during hospitalization. The total number and number of X, D, C, and B categories of pDDIs were the highest during hospitalization and the lowest on admission. Duration of hospitalization, arrhythmias, dementia, renal failure, cancer, surgery during hospitalization, number of prescribed drugs, and various pharmacological drug classes were risk factors for a higher number of pDDIs, while age, ischemic heart disease, hypertension, and development of infection during hospitalization were protective factors in at least one of the stages. The impact of renal colic depended on the stage and category of pDDI.

Conclusion: More than half of the urological patients were exposed to at least one pDDIs at all stages. Medical professionals should regularly screen for pDDIs, particularly in patients with risk factors.

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects various body systems, including the skin and facial features. Estrogen promotes lupus in human and mouse models of SLE. In this study, we conducted an in vivo study to investigate the relationship between two estrogen receptors (ER_α and ER_β) and platelet-activating factor acetylhydrolase (PAF-AH) on the symptoms of SLE.

Methods: Skin and facial features, serum PAF-AH activity, tumor-necrosis factor-alpha (TNF-α), and anti-double stranded DNA (anti-dsDNA) antibody titer, all of which are central to the classification and pathogenesis of SLE, were measured in SLE model mice injected with various ER antagonists.

Results: In SLE mice, the injection of an ER_β antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidine-3-yl]-phenol induced the expression of facial erythema (especially around a cheek). The injection of an ER_α/β antagonist tamoxifen induced hair-loss on the head and the neck. The injection of an ER_α antagonist methylpiperidino pyrazole or tamoxifen increased PAF-AH activity and decreased TNF-α levels and anti-dsDNA antibody in mouse serum.

Conclusions: The activation of ER_α and inactivation of ER_β can cause inflammatory and cutaneous symptoms of SLE, respectively, implying that ER_α antagonists and/or ER_β agonists can be useful for the prevention and treatment of SLE.