Pakistan journal of pharmaceutical sciences最新文献

Objectives: This study aimed to evaluate the added benefits of a structured nutritional intervention combined with dapagliflozin in patients with DN.

Methods: In this prospective, randomized, open-label trial, 108 patients with DN were assigned to a control group (CG, conventional care), a treatment group (TG, CG + dapagliflozin 10 mg/day), or an observation group (OG, TG + Mediterranean diet and oral nutritional supplements). Key outcomes included glycaemic control (FBG, PBG, HbA1c), renal function (BUN, sCr, UACR, eGFR), nutritional status (albumin, ferritin, SGA), inflammation (CRP, TNF-α, IL-6), safety and quality of life (SF-36), assessed at baseline, 3 and 6 months.

Results: Both TG and OG showed significant improvements over CG in glycaemic control and renal parameters (P<0.05). The OG demonstrated superior outcomes compared to TG: greater reductions in HbA1c (-1.5% vs. -0.9%), FBG, PBG and UACR (-48% vs. -35%) (all P<0.05). Nutritional markers (albumin, ferritin) and SF-36 scores improved significantly more in the OG. Inflammatory markers decreased in both treatment groups, with a trend favoring OG. Adverse event rates did not differ significantly among groups.

Conclusion: Adjunctive nutritional intervention significantly enhances the glycaemic, renal, nutritional and quality-of-life benefits of dapagliflozin in patients with DN, offering a promising integrated therapeutic strategy.

Background: Osteoporosis (OP) is closely related to osteoblast damage and abnormal activation of ferroptosis.

Aims: To investigate whether natural polyphenolic compound syringaresinol (Syr) improves OP by activating the Nrf2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway.

Methods: A dexamethasone (DEX)-induced osteoblast injury model of MC3T3-E1 was established and the impacts of Syr on cell viability were assessed using Cell Counting Kit-8 and lactate dehydrogenase (LDH) assay. Osteogenic differentiation of MC3T3-E1 cells was assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining and different kits. Oxidative stress factors and Fe2+ content were examined by flow cytometry and different kits. The levels of bone formation, ferroptosis and Nrf2/SLC7A11/GPX4 pathway-related proteins were examined through western blot.

Results: Syr at concentrations of 25, 50, and 100 μM did not negatively impact MC3T3-E1 cell viability, and was able to enhance the viability of DEX-treated MC3T3-E1 cells and inhibit LDH release. Syr effectively increased ALP activity and ARS stained area and up-regulated bone formation marker proteins in MC3T3-E1 cells. Additionally, Syr inhibited oxidative stress and decreased ferroptosis-related protein levels. Notably, Syr activated Nrf2/SLC7A11/GPX4 pathway. Silencing Nrf2 impaired the ameliorative impact of Syr on osteogenic function and caused oxidative stress and ferroptosis.

Conclusion: Syr inhibits ferroptosis, promotes osteogenesis in MC3T3-E1 cells and ameliorates DEX-induced OP by activating Nrf2/SLC7A11/GPX4 pathway.

Background: Sepsis-associated acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disorder with high mortality. Bruceine A (BA), a quassinoid from Brucea javanica, exhibits anti-inflammatory and immunomodulatory activities, but its role in ARDS is unclear.

Objectives: This study evaluated the protective effects of BA in lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms.

Methods: Thirty-six C57BL/6 mice were randomized into four groups: Control, LPS, LPS+BA and LPS+dexamethasone (Dex). Lung injury was assessed by histopathology, wet/dry weight ratio and TUNEL assay. Cytokine levels (TNF-α, IL-6, IL-1β, IL-10) were measured by ELISA. Macrophage polarization markers (iNOS, COX-2, Arg-1, YM1, CD206) and NF-κB pathway proteins were evaluated using immunohistochemistry and Western blotting.

Results: BA significantly alleviated LPS-induced lung injury, reducing edema, tissue damage and alveolar apoptosis. It suppressed proinflammatory cytokines while enhancing IL-10. BA shifted macrophage polarization from proinflammatory M1 toward anti-inflammatory M2 phenotypes. Furthermore, BA inhibited NF-κB activation, evidenced by reduced phosphorylated p65 and restored IκBα levels. These effects were comparable to Dex.

Conclusion: BA protects against LPS-induced ARDS in mice by modulating cytokine release, promoting M2 macrophage polarization and suppressing NF-κB activation. These findings suggest BA as a promising natural immunomodulatory agent for inflammatory lung diseases.

Background: Luffa cylindrica flower has been used to treat haemorrhoids and breast hyperplasia, but the mechanism is unclear.

Objectives: In this study, the antiproliferation activity of L. cylindrica flower extract (LCFE) was tested in breast cancer cells.

Methods: Following LCFE treatment, the CCK-8 assay, Hoechst staining and wound healing assay were used to evaluate cell proliferation, apoptotic cell morphology, and cell migration, respectively. qRT-PCR and western blot were used to analyze the expression of genes and proteins involved in the apoptosis and autophagy pathways. LC-MS was performed to characterize chemical constituents of LCFE.

Results: CCK-8 and wound healing assays revealed that LCFE suppressed the proliferation and migration of MCF-7 and MDA-MB-231 cells. In these two breast cancer cells, the extract treatment induced apoptotic morphological changes. LCFE treatment induced apoptosis by upregulating ZFP36 and BNIP3 expression, while downregulating Bcl-2 expression in MCF-7 cells. LCFE increases ZFP36 expression while decreasing BMP4 expression in MDA-MB-231 cells, promoting apoptosis. Meanwhile, LCFE treatment induced autophagy by increasing VMP1 expression and activating LC3 in MCF-7 cells. It also triggered autophagy by decreasing TBC1D14 expression, increasing ATG5 and VAMP8 expression, and activating LC3 in MDA-MB-231 cells.

Conclusion: LCFE exerts an anti-tumor effect by activating apoptosis and autophagy processes in breast cancer cells, while having low cytotoxicity for normal breast cells, highlighting the potential of LCFE as a natural agent for cancer treatment.

Background: The rising prevalence of mild myopia among kids needs very effective methods for preventing its progression. Recent research suggests that a combination of acupuncture and a small dose of atropine eye drops might be more effectively combined for myopia control. The trial will evaluate myopia control among kids aged 6-14 years old using buried needle acupuncture with low-dose atropine 0.01%.

Objectives: To evaluate if there is a synergistic effect from periocular acupuncture and low doses of atropine on mild myopia in children 6-14 years old.

Methods: A total of 80 children with mild myopia and 160 eyes were included in the randomized controlled trial from March 2020 to June 2021. All participants were then randomly assigned equally into both the treatment group, which included acupuncture and low doses of atropine and routine eye care, and the control group, which included sham acupuncture and routine eye care. The main outcomes were uncorrected visual acuity, best-corrected visual acuity, spherical equivalent refraction, amplitude and facility of accommodation, and axial length. All these were measured at 0, 2, 6, and 12 months. Treatment compliance and attendance were monitored.

Results: The treatment group showed marked improvement in UCVA and BCVA, accommodation function, and rate of SER and axial length progression compared with the control group (P < 0.05). There were no serious side effects; two patients complained of mild transient pain. The combination regimen was generally tolerated without serious ocular or systemic side effects.

Conclusion: Periocular acupuncture with low dose atropine solution (.01%) seems to be a safe and more effective method as compared with conventional treatment alone for controlling mild myopia in children. Large scale trials should be conducted for validating these findings.

Background: Postoperative xerophthalmia (XER) following cataract surgery significantly impacts patient prognosis and quality of life, with traditional artificial tears offering limited efficacy.

Objectives: This study investigates the therapeutic effects and molecular mechanisms of recombinant human epidermal growth factor (rhEGF) combined with hydroxyglycoside.

Methods: A total of 164 patients were enrolled: A control group treated with hydroxyglycoside and an observation group treated with rhEGF combined with hydroxyglycoside. Before and after treatment, the tear film break-up time, Schirmer test, corneal fluorescence staining and other indicators were detected, and the levels of serum inflammatory factors and oxidative stress markers were measured in the two groups. At the same time, the dry eye rat model was established, and the rats were divided into groups for intervention. The pathological changes of corneal tissues were observed by HE staining, and the expressions of ERK/NF-KB pathway related proteins were detected by Western blot.

Results: After 8 weeks of treatment, there was no significant difference in the overall response rate between the two groups (P>0.05). However, the observation group demonstrated a significantly higher and good response rate compared to the control group (P<0.05). Furthermore, the observation group demonstrated superior tear film function compared to the control group post-treatment (P<0.05). Blood sample analysis revealed greater reductions in serum inflammatory factors and oxidative stress markers, along with significantly higher superoxide dismutase activity in the observation group (P<0.05). Finally, animal experiments further confirmed that rhEGF combination therapy mitigates corneal epithelial damage, inhibits inflammatory cell infiltration and reduces the expression of phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated NF-κB (p-p65) in corneal tissue.

Conclusion: This combination therapy offers a potential treatment strategy for postoperative XER following cataract surgery.

Background: Spinal cord injury (SCI) is a severe condition causing sensory, motor, and autonomic dysfunctions, with over 759,000 patients and 66,374 new cases yearly in China. Secondary injury, driven by inflammation and apoptosis, hinders neurorestoration, making treatment challenging. Schisantherin B (SCHB), an active component of the traditional Chinese medicine Schisandra chinensis, has anti-inflammatory and anti-apoptotic effects in cerebrovascular and neurodegenerative diseases but its role in SCI remains unstudied.

Objectives: This study aimed to investigate SCHB's therapeutic effects on SCI and clarify its underlying molecular mechanism, focusing on the PI3K/AKT signaling pathway.

Methods: In vitro, H₂O₂-induced PC12 cell apoptosis models were treated with different SCHB concentrations; cell viability (microplate reader), apoptosis (flow cytometry, immunofluorescence for cleaved caspase-3), and PI3K/AKT activation (immunofluorescence) were detected. In vivo, mouse SCI models (12.5g weight-drop contusion) received 15mg/kg SCHB intravenously; motor function (Basso Mouse Scale, footprint analysis), tissue damage (HE/Nissl staining), apoptosis (TUNEL staining), inflammation (ELISA for TNF-α/IL-1β/IL-6/IL-10), and PI3K/AKT activation (Western blot, immunofluorescence) were assessed.

Results: SCHB (25μM in vitro) increased PC12 cell viability (66.15% vs. 40.86% in H2O2 group), reduced apoptosis (5.84% vs. 10.81%), and upregulated PI3K/AKT proteins. In mice, SCHB improved BMS scores (21/28 days post-injury), increased stride length/width, reduced spinal cord cavity size, preserved motor neurons, lowered pro-inflammatory cytokines (TNF-α/IL-1β/IL-6), elevated IL-10, and activated the PI3K/AKT pathway.

Conclusion: SCHB exerts therapeutic effects on SCI by inhibiting inflammation and apoptosis via activating the PI3K/AKT signaling pathway, supporting its potential as a candidate for SCI treatment.

Background: The cross-disciplinary integration of sports and medicine has become an important trend. This integration not only creates conditions for optimizing disease treatment plans and enhancing the efficacy of drug therapy, but also provides a new path for promoting public health and improving the efficiency of health resources.

Objective: The integration of sports and medicine offers opportunities to optimize drug therapies and improve health outcomes.

Method: This study applies structural equation modeling to analyze the interplay between sports activity, pharmaceutical interventions and health promotion. By integrating quantitative and qualitative indicators-such as resource allocation, participation rates and drug utilization patterns-the research identifies pathways to enhance collaborative governance in sports-medicine fusion.

Results: Strategic investment in sports and medicine can jointly enhance medication compliance, health outcomes, and resource utilization efficiency, and has clarified the key path for promoting the collaborative governance of sports and medicine integration.

Conclusion: The research results provide a basis for formulating comprehensive policies that integrate physical exercise and drug intervention, which is conducive to promoting the deep integration of sports and medicine and achieving an improvement in the overall health level of the population.

Background: Calcaneal fracture (FOC) is a common foot trauma. Severe postoperative pain can easily trigger the body's stress response, increase the risk of thrombosis, and seriously affect the recovery of patients. Sciatic nerve block (SNB) guided by traditional nerve stimulator (NS) has some problems such as inaccurate positioning and unstable block effect. Ultrasound-guided technology can visualize the nerve structure and puncture process in real time to improve the accuracy of block.

Objective: In this study, we observed the analgesic effect of ropivacaine SNB on FOC under the guidance of ultrasound combined with a NS.

Methods: We retrospectively analyzed 200 FOC patients, including 113 patients who received ropivacaine SNB guided by ultrasound combined with an NS (ultrasound group) and 87 patients who received ropivacaine SNB under the guidance of an NS (conventional group).

Results: The ultrasound group showed a shorter onset time of anesthesia and a greater number of grade I (the block was successful and the patient had no obvious pain and muscle relaxation) anesthetic effect in patients (P<0.05). At 30 minutes after analgesia and 60 minutes after analgesia, the vital signs of the ultrasound group were more stable. In addition, the stress response indexes Epinephrine (E) and Cortisol (Cor) in the Ultrasound group were lower than those in the conventional group (P lt;0.05) and coagulation function indexes were higher than those in the conventional group (P lt;0.05). Finally, the incidence of adverse reactions in the ultrasound group was lower than that in the conventional group (10.34% vs. 2.65%, P lt;0.05).

Conclusion: Ultrasound-guided ropivacaine SNB combined with NS has a good analgesic effect in analgesia after FOC surgery.

This study aimed to explore the effect of a targeted collaborative nursing scheme of antimicrobial agents combined with physical cooling on drug efficacy and patient comfort during the postoperative infection period of orthopedic patients. A total of 150 patients with postoperative infection in the Department of Orthopedics of Zhejiang Provincial Tongde Hospital from January 2023 to January 2024 were selected and randomly divided into a control group (75 cases) and an observation group (75 cases). The control group received conventional antimicrobial treatment and basic nursing care, while the observation group received a collaborative nursing program of antimicrobial treatment combined with physical cooling on the basis of the control group. Compared with the control group, the observation group showed significantly shorter onset time, infection control time and temperature recovery time of antimicrobial drugs (P<0.05); significantly higher General Comfort Questionnaire (GCQ) scores (P<0.05); significantly lower incidence of adverse reactions (P<0.05); and significantly higher blood concentration compliance rate of different antimicrobial drugs (P<0.05). This collaborative nursing can significantly improve the efficacy of antimicrobial drugs, accelerate infection control, enhance patient comfort and reduce the risk of adverse reactions, with important clinical promotion value from a pharmaceutical perspective.