Journal of Clinical Pharmacy and Therapeutics最新文献

Background: Wen-Jing-Zhi-Tong decoction (WJZTD) is a traditional Chinese medicine herbal decoction that has demonstrated clinical efficacy in treating primary dysmenorrhea (PDM) over decades. However, the underlying therapeutic mechanism of WJZTD requires further clarification.

Objective: This study aims to explore and elucidate the therapeutic mechanism of WJZTD in treating PDM through metabolomics, integrated network pharmacology, as well as in vitro and in vivo experiments.

Methods: A PDM rat model was established by estradiol benzoate and oxytocin for 3 consecutive estrous cycles, and then WJZTD treatment was administered for 3 consecutive estrous cycles. To evaluate the therapeutic effect of WJZTD on PDM, behavioral tests, histological analysis, and evaluation of serum prostaglandins (PGs) were performed. Moreover, immunofluorescence and Western blot analysis were carried out in dorsal root ganglion (DRG) tissues to explore the role of WJZTD in reducing pain sensitivity. Metabolomics and integrated pharmacology were utilized to identify potential bioactive targets, which were then validated through in vitro experiments.

Results: WJZTD significantly reduces pain sensitivity in PDM rats, treating the condition effectively by decreasing brain-derived neurotrophic factor (BDNF) protein expression, c-Fos-positive neurons in DRG, and serum prostaglandin PGF2α (PGF2α) levels. A nontargeted metabolic analysis identified 11 differential metabolites, suggesting ESR1 (estrogen receptor α, ERα) as a potential target. In vitro experiments confirmed WJZTD’s efficacy in treating PDM through regulating the ERα/BDNF signaling pathway.

Conclusion: WJZTD decreases the excitability of DRG neurons in rats with PDM through the ERα/BDNF pathway, which enhances pain sensitization and contributes to reducing dysmenorrhea.

Objective: Serum lactic acidosis has been reported as a serious adverse effect associated with linezolid. This study aims to explore the risk factors of linezolid-induced lactic acidosis.

Methods: Patients admitted to a 3600-bed university hospital, who received linezolid treatment and had at least one steady-state concentration of linezolid, were retrospectively reviewed to analyze the incidence of linezolid-induced lactic acidosis. Meanwhile, univariate and multivariate logistic regression analyses were conducted to determine the risk factors of lactic acidosis.

Results: A total of 95 adult patients were included in the study. 18.95% (18 out of 95) of patients developed lactic acidosis during linezolid treatment. Importantly, patients who concurrently used linezolid and metformin had a high risk of developing lactic acidosis (90.9%, 10 out of 11). After excluding these patients from the original database, 9.52% (8 out of the 84) of the patients developed lactic acidosis. In the population not receiving concurrent metformin treatment, univariate analysis showed that patients who developed lactic acidosis had higher linezolid C_min and serum creatinine levels or lower creatinine clearance, and multivariate analysis showed that C_min (OR: 1.114; 95% CI: 1.012–1.226; p = 0.027) was an independent risk factor for lactic acidosis.

Conclusion: The concurrent use of linezolid and metformin raises the risk of lactic acidosis. Therapeutic drug monitoring of linezolid based on C_min is recommended for decreasing the risk of lactic acidosis during linezolid treatment.

Objective: Many biological or targeted synthetic disease-modifying anti-rheumatic drugs (b/ts DMARDs) are used in the treatment of psoriatic arthritis (PsA) during recent years, but there are few head-to-head studies that directly compare these drugs to evaluate and compare the relative efficacy of these treatments at week 24. The aim of this study is to conduct a comprehensive comparison of all clinically used bDMARDs or tsDMARDs for PSA using a network meta-analysis to evaluate relative efficacy of these drugs, which is evaluated by ACR20, ACR50, ACR70, PASI75, and PASI90.

Methods: All randomized controlled trials of these treatments are searched in PubMed, Web of Science, and Embase, and data are extracted from the included articles, and network meta-analysis is performed using the Stata 13 software.

Results: secukinumab 300 mg is the top-ranked treatment for ACR20 and PASI90, infliximab 5 mg/kg is the top-ranked treatment for ACR50, and adalimumab 40 mg is the top-ranked treatment for ACR70 and PASI75.

Conclusions: Tumor necrosis factor-α inhibitors and interleukin 17A inhibitors are the top-ranked treatments for arthritis and skin responses of active PsA.

Backgrounds: Quercetin has potentially beneficial therapeutic effects for several chronic, inflammatory disorders of the airways. Thus, we explore the therapeutic value and mechanism of quercetin in the treatment of asthma and pulmonary fibrosis overlap syndrome after COVID-19.

Methods: The potential targets and molecular mechanisms of quercetin for the treatment of overlap syndrome were predicted using a network pharmacology method. The binding mechanism between the core potential compounds and their targets was predicted using molecular docking with AutoDock Vina. An asthma model induced by ovalbumin was built to evaluate the effect of quercetin on asthma.

Results: 55 common targets and eight key genes between the overlap syndrome and quercetin were obtained for further study. Most of the interested target genes were mainly focused on inflammation-related signaling pathways. Via molecular docking, quercetin showed a high degree of affinity for TNF, IL-6, and MMP9. In addition, quercetin improved asthma symptoms, inflammatory response, and pulmonary fibrosis.

Conclusion: This study, which examined the use of quercetin for the treatment of the overlap syndrome of asthma and pulmonary fibrosis following COVID-19 from the aspect of network pharmacology, might serve as a useful guidepost for future studies and clinical applications.

Backgrounds: The Zao Ren An Shen (ZRAS) Capsule, stemming from a traditional Chinese herbal formula, is recognized as a safe and effective sleep-regulating medication. Asthma often worsens during the night and early morning due to its distinct day–night rhythm, suggesting the potential for the ZRAS Capsule to intervene in asthma attacks and prognosis. Since inflammation is a primary mechanism in asthma, exploring the anti-inflammatory effects of the ZRAS Capsule is essential.

Methods: This study identifies the intersection of ZRAS Capsule-related targets and anti-inflammatory targets to uncover potential anti-inflammatory mechanisms. Core compounds and relevant genes were identified using protein–protein and compound–protein interaction networks. KEGG pathway and Gene Ontology analyses were performed on the anti-inflammatory targets to validate their role in mitigating asthma inflammation. Binding activities between the compounds and anti-inflammatory targets were assessed using western blot, qRT-PCR, molecular docking, and immunohistochemistry (IHC).

Results: Key compounds, including luteolin, (S)-Coclaurine, and zizyphusine, along with targets IL6, TNF, and MMP9, were identified. Their biological processes were linked to the IL-17 signaling pathway and TNF signaling pathway. Notably, the identified compounds inhibited the mRNA and protein expression of IL6, TNF, and MMP9.

Conclusion: Regulation of the IL-17/TNF signaling pathway is likely crucial for the protective effects of the ZRAS Capsule in asthma treatment.

Objective: To explore the effect and mechanism of pirfenidone (PFD) on lung injuries in newborn rats caused by intrauterine inflammation.

Methods: In vivo, we established the intrauterine inflammation model with lipopolysaccharide (LPS) injection in pregnant rats. The administration of PFD in pregnant rats was performed to evaluate its beneficial effect against intrauterine inflammation-induced lung injuries in neonatal rats. Lung tissues of newborns from three groups of pregnant rats (Saline + DMSO, LPS + DMSO, and LPS + PFD) were collected. Immunohistochemistry (IHC) and Western blot were used to detect the fibrotic-related protein expressions. In vitro, LPS-induced mouse lung epithelial cells (MLE 12) were employed to explore the underlying mechanism of PFD against intrauterine inflammation-induced lung injury in neonates.

Results: In vivo, the radial alveolar count (RAC) was decreased, the mean linear intercept (MLI) was increased, and the lung injury score was high in intrauterine inflammation (LPS + DMSO-treated pregnant rats) induced lung injuries in newborns. The protein level of matrix metallopeptidase 9 (MMP-9), TGF-β1 (transforming growth factor beta 1), phospho-Smad2 (Sma- and mad-related protein 2), and phosphor-Smad3 (Sma- and mad-related protein 3) levels were upregulated in neonatal lungs with intrauterine infection. Lung injuries were alleviated in LPS + PFD groups, and the protein levels of TGF-β1, p-Smad2, p-Smad3, and MMP-9 were reduced. In vitro, PFD attenuated the LPS-induced inflammatory response and reduced the expressions of MMP-9, TIMP-1, and Collagen IV in lung epithelial cells through the TGF-β1/Smad2/3 signaling pathway.

Conclusions: PFD alleviates intrauterine infection-induced lung injuries in neonates by targeting transforming growth factor beta 1/Sma- and mad-related protein signaling pathway. The inhibition of TGF-β1 signaling by PFD prevents the neonatal lung injuries by reducing MMP-9 and Collagen IV protein levels. This study provides theoretical basis and insights for PFD-mediated intervention of lung injury in neonates with intrauterine infection.

Background: The rise of drug-resistant bacteria poses a significant challenge to global healthcare, underscoring the urgent need for new therapeutic interventions. In this study, ethanolic extracts of Datura stramonium and Prosopis farcta, sourced from Northern Iran, were examined for their antibacterial properties against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Methods: The antibacterial activities of the medicinal extracts were examined in this study using disc diffusion, microbroth dilution, and agar well diffusion methods against both Gram-positive and Gram-negative microorganisms. In addition, the extracts were assessed for toxicity using the MTT assay on HT29 cells. The biofilm-inhibitory effects of the extracts were also investigated.

Results: The results showed that the ethanolic extracts from D. stramonium and P. farcta have strong antibacterial activity against S. aureus. However, their activity against P. aeruginosa and A. baumannii is less pronounced. The extracts showed significant antibiofilm capabilities against the tested bacteria at both MIC and 2× MIC concentrations (p < 0.05). The MTT test showed HT29 cells were more sensitive to P. farcta extract than D. stramonium, especially at 200 μg/mL concentration.

Conclusion: The findings demonstrate that ethanolic extracts of P. farcta and D. stramonium exhibit significant antibacterial activity, particularly against S. aureus, while also effectively disrupting bacterial biofilms. These results suggest that these extracts possess considerable potential as alternative therapeutic agents against drug-resistant bacterial infections. Further investigation is warranted to elucidate the specific mechanisms of action and to explore their efficacy in clinical applications.

Background: Pharmacological sedation during neonatal magnetic resonance imaging (MRI) is crucial for procedure success and minimizing artifacts. Hence, it is vital to evaluate the effectiveness and safety of conventional sedatives in this population. In this study, we aim to evaluate the effectiveness of oral chloral hydrate combined with intranasal dexmedetomidine in neonatal MRI.

Methods: Neonates aged 0 to 28 days undergoing MRI were enrolled and received intranasal dexmedetomidine followed by oral chloral hydrate. Subsequently, sedation scores, onset time, and overall time of sedation, as well as any potential adverse reactions, were recorded.

Results: All neonates completed the MRI without notable adverse reactions. 128 neonates (90.1%) completed the MRI study with a single dose, while 14 neonates (9.9%) required additional medications. In the neonates with a single dose, no statistically significant differences in onset time were observed across postnatal days, gender, and weight. And no statistically significant differences in total time were observed across postnatal days and gender. However, the total time was significantly extended in the neonates with a weight under 3 kg. Furthermore, compared to the neonates with a single dose, the total time was significantly extended in the neonates with additional medications.

Conclusion: Oral chloral hydrate combined with intranasal dexmedetomidine is effective and safe for neonatal MRI, but extra attention is needed for neonates under 3 kg.

To overcome TRAIL resistance, we tested the antidepressant drug citalopram (CTL) in combination with TRAIL. The resistance of several types of cancer cells to TRAIL impedes TRAIL-induced cancer cell death. In this study, we investigated the role of, and molecular mechanism by which, the antidepressant CTL-induced cell death in TRAIL-resistant lung cancer cells. We found that CTL increased death receptor 5 (DR5) expression levels by impairing autophagic flux and protecting against lysosomal degradation, thereby increasing the TRAIL-induced apoptosis of TRAIL-resistant A549 lung cancer cells. We also found that CTL impaired autophagic flux and promoted the conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, thereby inducing autophagosome accumulation. Our hypothesis that impaired autophagic flux plays an important role in the upregulation of DR5 being confirmed when we determined that DR5 upregulation by CTL was markedly decreased in the presence of rapamycin, an autophagy inducer. Further verification of our theory was achieved through experiments pairing CTL with the early-stage autophagy inhibitor 3-methyladenine (3-MA) and the late-stage autophagy inhibitor chloroquine (CQ). CQ inhibits autophagy by impairing autophagosome–lysosome fusion. Both CTL and CQ markedly increased DR5 expression levels and increase TRAIL-induced apoptosis, whereas 3-MA marginally enhanced TRAIL-induced apoptosis and resulted in minimal DR5 expression. In summary, our findings indicate that CTL impairs autophagic flux, resulting in autophagosome accumulation and augmentation of DR5 to potentiate TRAIL-induced apoptosis, suggesting that CTL may act as a therapeutic agent that sensitizes TRAIL-resistant cancer cells to TRAIL-mediated cancer therapy.

What Is Known and Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal and cardiovascular outcomes and have been reported to have a positive impact on anemia, a common and challenging condition in patients with chronic kidney disease (CKD). The aim of this study is to evaluate the effects of SGLT2 inhibitors on anemia in patients with CKD.

Methods: We performed a systematic review and meta-analysis of randomized controlled trials. Changes in hemoglobin (Hb) and hematocrit (Hct) levels were assessed in participants treated with SGLT2 inhibitors—empagliflozin, dapagliflozin, or canagliflozin—and compared with those receiving control treatments. Statistical analyses were performed using a fixed-effects model or a random-effects model, depending on the heterogeneity. Sensitivity analyses were also conducted to evaluate the impact of each study on the meta-analysis. Publication bias was examined using Begg’s and Egger’s tests.

Results and Discussion: Five studies assessing Hb levels were included. SGLT2 inhibitors significantly increased Hb levels compared with controls (standard difference in means [SE] = −0.350; 95% confidence interval [CI] −0.401–−0.299). Similarly, in three studies evaluating Hct levels, SGLT2 inhibitors significantly increased Hct levels compared with controls (SE = −0.453; 95% CI −0.829–0.077).

What Is New and the Conclusions: This systematic review confirms that SGLT2 inhibitors effectively improve anemia in patients with CKD. We recommend considering SGLT2 inhibitors as a treatment option for CKD patients, not only for their renal and cardiovascular benefits but also for their reliability in addressing anemia.