Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Given the high incidence of apnea of prematurity (AOP) and the repeated hypoxia-induced nerve damage, treatment optimization from the dosing perspective is critical. Caffeine is the current first-line therapeutic drug for AOP. However, the conventional dose results in low blood concentration compliance, with significant variation among individuals. Objectives: To explore the clinical efficacy and safety of a therapeutic drug monitoring (TDM)-guided individualized caffeine dosage regimen and its association with early neurobehavioral development and weight gain in preterm infants (PTIs). Methods: In this retrospective propensity score-matched cohort study, 130 PTIs with AOP were included after 1:1 matching, with 65 infants in the TDM-guided individualized dosing group and 65 in the conventional fixed-dose group. Inter-group comparative assessments were conducted from the perspectives of blood drug concentration compliance rates, apnea control, adverse reactions, neurobehavioral development scores, clinical outcomes and weight gain rates. Results: Compared with the conventional fixed-dose group, the TDM-guided individualized dosing group had a significantly higher target attainment rate of blood caffeine concentration (92.31% vs 70.77%; OR=5.22, 95% CI 1.68-12.74, P=0.002), lower apnea episode frequency at 4 weeks (MD -1.40 times/day, 95% CI -2.13 to -0.67, P<0.001), lower overall incidence of adverse reactions (6.15% vs 20.00%; OR=0.26, 95% CI 0.09-0.87, P=0.035), higher NBNA score at 40 weeks of corrected gestational age (MD 1.74, 95% CI 1.23-2.25, P<0.001), shorter hospital stay (MD -4.11 days, 95% CI -6.51 to -1.71, P=0.001) and faster weight gain rate (MD 7.88 g/day, 95% CI 3.21-12.55, P=0.001). Conclusion: The TDM-guided individualized caffeine dosing regimen was associated with improved precision of AOP treatment, better short-term therapeutic efficacy and safety, and higher early neurobehavioral assessment scores and weight gain in preterm infants within 6 months of corrected gestational age. Multicenter studies with longer follow-up are needed to further verify its long-term clinical benefits.

Abstract: Background: Postoperative chemotherapy for breast cancer often leads to intestinal dysbiosis and immune suppression. Traditional Chinese medicine shows potential in regulating gut microbiota and enhancing immune function, offering a promising adjunctive therapeutic strategy. Objectives: To explore the effects of a traditional Chinese medicine compound on the recovery of intestinal bifidobacteria and CD4+ T-cell activation in breast cancer patients undergoing postoperative chemotherapy. Methods: Female patients with newly diagnosed breast cancer were randomly assigned to a control group (triamcinolone tablets) and an observation group (control treatment plus kidney-tonifying and compound traditional Chinese medicine soup). Intestinal flora and immune indices were measured and analyzed using SPSS 22.0. Results: After chemotherapy, the observation group showed significant increases in bifidobacteria to 9.01±1.49 lg (CFU/g) and in CD4+ T-cell counts to 969/μL. The expression levels of peripheral blood CD4+ T cells and the differences in S2, nm23 and Her-2 indices were significant between the groups, with the observation group showing greater CD4+ T cell activation. The incidence of adverse reactions was significantly lower in the observation group (P-values: 0.002, 0.006 and 0.030). The observation group also demonstrated better control of gastrointestinal conditions and disease progression (P<0.001). Conclusion: The traditional Chinese medicine compound effectively maintained intestinal flora balance, promoted beneficial bacterial growth, reduced adverse reactions and offered better therapeutic prospects for breast cancer patients.

Abstract: Background: Fracture healing is a dynamic biological process involving inflammation, callus formation, mineralization and remodeling. Osteogenic and apoptosis-related markers may reflect changes during repair, but tissue-level marker expression alone does not establish a causal apoptotic mechanism. Objectives: To evaluate whether Compound Miao medicine Jiuxian Luohan bone-setting decoction is associated with improved femoral fracture healing in rats and with altered expression of runt-related transcription factor 2 (Runx2), Osterix, procollagen type I N-terminal propeptide (PINP), Bcl-2-associated X protein (Bax) and Caspase-3 at the fracture site. Methods: Twenty-five male specific-pathogen-free (SPF) Sprague-Dawley rats were used to establish a right femoral fracture model and were randomized into five groups (n=5/group): model, low-, medium- and high-dose decoction and orthopedic bone-setting tablet groups. Treatments were initiated 24 h after modeling and administered by gavage twice daily for 30 days. Anteroposterior and lateral radiographs were obtained on day 15 and scored using the Lane-Sandhu system. Fracture-site tissues were collected on day 30 for reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry and Alizarin Red staining. Results: Compared with the model group, the high-dose decoction group showed a higher Lane-Sandhu score at week 2 and greater callus formation. Runx2, Osterix and PINP mRNA/protein levels increased, whereas Bax and Caspase-3 mRNA/protein levels decreased in treated groups, particularly in the high-dose group. Alizarin Red staining indicated greater deposition of mineralized matrix in treated tissues. Conclusion: Compound Miao medicine Jiuxian Luohan bone-setting decoction was associated with improved radiographic healing and favorable changes in osteogenic and apoptosis-related markers in this rat femoral fracture model.

Abstract: Macrophage functional states are increasingly viewed as a dynamic spectrum rather than a fixed M1/M2 dichotomy. Astragalus polysaccharides (APS) are structurally heterogeneous natural polysaccharides with reported immunomodulatory, anti-inflammatory, antioxidant, antitumor and tissue-repair activities; however, their structure-activity relationships, receptor-recognition mechanisms and translational readiness remain incompletely defined. This review summarizes mechanistic and translational evidence for APS-mediated regulation of macrophage functional states, with emphasis on structural heterogeneity, innate immune recognition, pathway crosstalk, disease-context dependence and current barriers to clinical development. A narrative literature review was conducted using PubMed, Web of Science, Scopus, Google Scholar and selected publisher databases. The literature search focused on studies published between 2020 and 2026, with priority given to recent mechanistic, preclinical and translational studies addressing APS, macrophage activation, macrophage polarization, immunometabolism, oxidative stress and disease-specific immune remodeling. Predominantly preclinical evidence suggests that APS do not act as simple unidirectional inducers of M1- or M2-like polarization. Instead, APS appear to modulate macrophage functional states according to structural features, receptor engagement and disease context. TLR4/MyD88/NF-kappaB, MAPK, Notch, PI3K/Akt/Nrf2/HO-1, JAK/STAT, cGAS-STING, NLRP3 inflammasome and immunometabolic pathways form interconnected regulatory networks. Preclinical studies suggest that APS may promote antitumor inflammatory and antigen-presenting programs in tumors while attenuating excessive inflammatory activation and supporting reparative programs in diabetic vascular injury, acute kidney injury and chronic wounds. This review integrates APS structure-activity relationships with macrophage plasticity and translational limitations. Further progress toward clinical development would depend on high-purity fractionation, rigorous quality control, glycomics-based receptor mapping, single-cell and spatial validation, pharmacokinetic and safety studies and well-designed clinical investigations.

Abstract: Background: Bergenin (BN), a C-glucoside of 4-O-methyl gallic acid, exhibits a broad spectrum of pharmacological activities, including notable antioxidant, anti-inflammatory and anticancer effects. Objectives: This study aimed to explore the impact of polydopamine nanoparticles loaded with bergenin (PDANPs-BN) on glioma and their mechanisms of action. Methods: PDANPs-BN nanocomposites were prepared and U251 cells were cultured and divided into the BN group and the PDANPs-BN group. The biological processes of U251 cells were observed by using CASC11 mimic, si-CASC11 and agonists and inhibitors of AKT3. Results: Compared to free BN, PDANPs-BN significantly inhibited the malignant biological behavior of U251 cells, reducing the cell proliferation rate by approximately 45% and suppressing migration capacity by about 60% (P<0.05). Mechanistic studies revealed that PDANPs-BN downregulated CASC11 expression levels by 2.1-fold, thereby inhibiting AKT3 signaling pathway activity. The strongest antitumor effect was observed when combined with si-CASC11 and an AKT3 inhibitor. While the addition of an AKT3 agonist partially reversed this effect, cell proliferation remained suppressedand colony-forming ability was altered. Conclusion: PDANPs-BN acts by targeting the CASC11/AKT3 axis, resulting in downregulation of CASC11 and consequent inhibition of AKT3 signaling, which ultimately curbs the malignant progression of glioma.