Pakistan journal of pharmaceutical sciences最新文献

The global prevalence of schizophrenia is about 0.40% and in some parts of my country it is 0.54%-0.94%. Its treatment faces many difficulties. Antipsychotic drugs are commonly used treatments, but they have many side effects; repetitive transcranial magnetic stimulation (rTMS), as a non-invasive physical therapy, has a certain effect in improving mental and living abilities. This study used a randomized controlled trial to divide 100 patients into an experimental group (rTMS + drugs) and a control group (drugs only) and evaluated them with multiple scales. The relapse rate during the 24-month follow-up period was compared to evaluate rehabilitation and economic value. The results showed that the experimental group had lower Positive and Negative Syndrome Scale (PANSS), higher efficacy and lower relapse rates after treatment; both groups had improved quality of life and cognitive function-related indicators and the experimental group was more significant; the experimental group had higher Wisconsin Card Sorting Test (WCST) scores and better economic benefits; there were no serious adverse events in both groups. In summary, rTMS combined with antipsychotic drugs has good efficacy and safety in the treatment of schizophrenia, can improve patients' quality of life and economic benefits and provide a better choice for clinical treatment.

Fentanyl, a potent synthetic opioid analgesic, is commonly used to manage severe pain. However, the effects of fentanyl use on male reproductive health have not been adequately studied. This study aimed to investigate the effects of different doses of transdermal fentanyl patches on various reproductive parameters in male rats. Adult male Albino Wistar rats were divided into four groups. The treatment groups received transdermal fentanyl at doses of 25 mcg/h (Group II), 50 mcg/h (Group III), and 100 mcg/h (Group IV) for 9 days, respectively. Sperm motility, sperm concentration, abnormal sperm, live/dead sperm, testicular apoptosis, testicular oxidative stress, and androgen receptor levels were evaluated. The results showed that fentanyl administration decreased the oxidative stress parameters CAT and SOD1 levels in all treatment groups (p<0.001). No significant changes were observed in sperm motility, abnormal sperm ratio, or live/dead sperm ratio. However, Group IV showed a significant increase in sperm concentration compared to the other groups (p<0.001). In addition, all fentanyl treatment groups showed a significant increase in apoptosis-related Caspase 3/8/9 enzymes (p<0.001). This study reveals the effects of fentanyl on male reproductive health. This is the first study to demonstrate an increase in sperm concentration associated with high fentanyl doses.

The acute Kawasaki Disease (KD) is a pediatric condition that can cause significant cardiovascular damage, particularly affecting the coronary arteries. Recent research suggests that vitamin D regulates the immune responses and inflammation, potentially improving outcomes in KD. A randomized control trial involving 120 children aged 1-5 years assigned participants to either a treatment group (receiving intravenous immunoglobulin [IVIG], aspirin, and vitamin D; n=60) or a control group (receiving IVIG and aspirin only; n=60). Clinical symptoms, blood routine indices, and serum inflammatory markers (IL-1β, IL-6, and TNF-α) were assessed before and after treatment. Compared to the control group, the treatment group exhibited significantly faster fever resolution (antipyretic time: 27.2±1.3 hours vs. 50.4±2.4 hours in the control group, p < 0.001), lower incidence of IVIG adverse reactions (19 cases vs. 8 cases in the control group, p = 0.031), and reduced levels of inflammatory markers (WBC, CRP, ESR and platelet count). Additionally, the treatment group had lower post-treatment levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). These findings suggest that vitamin D supplementation may modulate the immune response and improve clinical outcomes in children with KD.

Silybum marianum (S. marianum) is famous for its nutritional value and medicinal benefits; while 1,4-dioxane is extensively used at the industrial level and in daily routine, but with all its uses, it is also becoming a major water contaminant with hazardous impacts on human health. The current study assessed the therapeutic potential of the ethanolic extract of S. marianum leaves against 1,4-dioxane induced hemato- hepato- nephrotoxicity in male Sprague-Dawley (SD) rats by involving 40 male SD rats, distributed into eight groups viz., control group (C), S. marianum extract groups (S1, S2 and S3 at 85, 165 and 247 mg/kg, respectively), positive control group (G1): treated with 1,4-dioxane at 3000 ppm, and three co-treated groups (G2, G3, G4: 1,4-dioxane at 3000 ppm + S. marianum at 85, 165 and 247 mg/kg, respectively). After the completion of the trial (60 days), significant (P<0.05) improvements in body weight, hepatic-, renal- and lipid profile as well as histo-architecture of liver and kidney were observed in co-treated groups in a dose-dependent manner. While 1,4-dioxane at 3000 ppm severely altered the selected parameters in SD rats. Conclusively, S. marianum, due to its therapeutic potential at 247 mg/kg, countermeasured the 1,4-dioxane induced hemato-, hepato- and nephrotoxicity in male SD rats.

Intracerebral hemorrhage (ICH) is a highly fatal neurological disease with few successful treatments. The aim of the current study was to investigate the neuroprotection by progesterone and the related molecular mechanisms following ICH. Mice were treated with progesterone (8 mg/kg), estrogen receptor (ER) agonist-erteberel (10 nmol/2 μL), or ER-β-specific siRNA (si-ER-β, 6 nmol/2 μL). Neurological function, edema in the brain and inflammatory cytokine levels were tested. Progesterone significantly increased neurological function on day 1 to day 7 post-ICH and reduced cerebral water content compared to the control group on day 7. Progesterone also suppressed estrogen receptor beta (ER-β) and decreased inflammatory mediator levels such as prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in ICH-evoked brain tissues and in LPS-stimulated BV-2 microglial cells. These anti-inflammatory effects were inhibited by erteberel, indicating direct interaction with ER-β signaling. Furthermore, progesterone treatment inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 via inhibition of ER-β. In summary, our findings show that progesterone is neuroprotective after ICH by modulating the ER-β/TLR4/NF-κB pathway and suggest its therapeutic value for managing post-ICH inflammation.

Docetaxel (Dtx) is a frequently used antineoplastic agent despite its dose-limiting toxic effects. Our objective was to assess the effects of oleuropein (Ole), a natural polyphenol, on Dtx-induced toxicity. Thirty-two male rats were randomly assigned to four groups for a four-week treatment: Control (sham), Dtx (5 mg/kg weekly, i.p.), Ole (30 mg/kg daily, p.o.) and Dtx+Ole. Biochemical and gene expression analyses were performed on liver, kidney and blood samples. Additionally, histological and immunohistochemical evaluations were conducted on the liver and kidneys. Ole reduced the Dtx-induced oxidative stress index in tissues. In contrast to Dtx, it decreased caspase-3 and Bax gene expressions while increasing Bcl-2 expression. Furthermore, Ole improved the ALT, AST, urea and creatinine levels, which were impaired by Dtx administration. It also reduced serum IL-6, IL-1β and TNF-α levels, which had been elevated due to Dtx. Histopathological and immunohistochemical examinations revealed that Ole administration mitigated Dtx-related damage in both tissues. These findings suggest that Ole might offer protection against Dtx-induced liver and kidney toxicity in rats.

Cantharidic acid (CA) has shown effective anticancer activity against many solid tumor cells, but it has not been reported in colorectal cancer (CRC). The PFKFB3 overexpression vector was transfected into SW480 and HT29 cells and the cells were treated with CA and PI3K activator 740 Y-P for 24 h. The malignant progression of the cells was evaluated through CCK-8, EdU, Transwell, flow cytometry, LDH release assay and Hoechst 33258 fluorescence. The expressions of aerobic glycolysis (AEG) and PI3K/Akt/P53 pathway were detected using the kit, extracellular acidification rate (ECAR) assay and Western blot. The subcutaneous tumor model was established by subcutaneous injection of SW480 cells. CA could significantly reduce the proliferation, migration and invasion of SW480 and HT29 cells and promote apoptosis and trigger cell cycle arrest. CA could reduce glucose uptake, lactic acid production and glycolytic capacity, reduce p-PI3K and p-Akt protein levels, raise P53 protein level. PFKFB3 overexpressed promoted CRC malignant progression. 740 Y-P could increase the AEG of CRC cells. Finally, CA reduced the volume and weight of CRC xenografts in mice and inhibited AEG and malignant biological behavior. In conclusion, CA inhibited AEG and malignant progression of CRC cells by regulating the PI3K/Akt/P53 pathway.

The plant Pandanus amaryllifolius Roxb (pandan), has been shown to have antidyslipidemic activity. This study showed the activity of various alkaloids and flavonoids from pandanus leaf that worked as antidyslipidemic. The in-vivo testing was done by taking the blood samples of normal and diabetic male albino rat and assessed the lipid profile. The molecular docking testing was done by the interactions of the alkaloids and flavonoids with the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, Peroxisome Proliferator Activator Receptor (PPAR) alpha and the Niemann Pick C1 Like 1 receptor (NPC1L1) at receptor 1HW9, 6LX4 and 7DFZ respectively. Analyses were carried out by studying the binding affinity of the different alkaloids (pandanamine, pandamarilactonine A and pandamarilactonine B) and flavonoids (catechin, epicatechin, epigallocatechin, kaemferol, myricetin, quercetin) present in pandan leaves. Cholestrol HDL ratio, triglycerides, VLDL decreased and HDL increased. The binding energy of alkaloids pandamarilactonine B at 6LX4 was -9.3 kcal/mol, at 7DFZ were -8.9 and at 1HW9 receptor binding energy of pandamarilactonine A was more negative as compared to standard drug simvastatin showed higher level of interaction between the above mentioned alkaloid, flavonoids and receptors. The studied concluded that pandanus alkaloids and flavonoids have marked good antidyslipidemic activity.

This study focused on the green synthesis of zinc oxide nanoparticles (ZnO-NPs) using the aqueous extract of C. graveolens and evaluated their antidiabetic activity. The extract served as both a reducing and capping agent. Synthesized ZnO-NPs were characterized by FTIR, XRD, SEM, and Zetasizer to determine their structural, morphological, and optical properties. Characterization confirmed the successful formation of spherical, crystalline ZnO-NPs with sizes ranging from 20-50 nm. FTIR spectra indicated the role of hydroxyl and carbonyl groups in nanoparticle stabilization. The antidiabetic activity of the ZnO-NPs was assessed through in vitro alpha-glucosidase and alpha-amylase inhibition assays. A concentration-dependent increase in alpha-glucosidase inhibition was observed, with inhibition rates of 67.8% at 50 µg/mL and 86.9% at 100 µg/mL. Similarly, alpha-amylase inhibition reached 81.7% at 100 µg/mL. These findings suggest that the enhanced activity may be due to the synergistic effects of zinc ions and phytochemicals from the plant extract. Overall, green-synthesized ZnO-NPs from C. graveolens demonstrate significant in vitro antidiabetic potential via dual enzyme inhibition. Further in vivo and clinical studies are recommended to confirm their therapeutic efficacy and safety, positioning them as a natural and cost-effective approach for managing type 2 diabetes.

Accurate noninvasive assessment of tumor grade and therapeutic response in HER2-positive breast cancer remains challenging. This prospective, single-center study aimed to evaluate the diagnostic value of multimodal MR functional imaging in grading malignant breast tumors and monitoring trastuzumab response. Eighty HER2-positive patients confirmed by IHC/FISH were enrolled, including 41 low-grade and 39 high-grade tumors (Nottingham grading system). Patients underwent comprehensive MR imaging, including diffusion tensor imaging, MR spectroscopy and perfusion imaging at baseline and during therapy. Tumor morphological features (size, necrosis, hemorrhage, edema, boundary clarity) and functional MR parameters (FA, tCho, MTT, TTP) were analyzed for correlation with pathological grade and treatment response. High-grade tumors showed larger size, more necrosis, hemorrhage and edema (P<0.05). Functional MR parameters, particularly tCho, MTT and TTP, correlated positively with tumor grade (P<0.05). ROC analysis demonstrated high diagnostic accuracy (sensitivity 89.2%, specificity 79.5%, AUC=0.887). Typical MR imaging patterns also reflected trastuzumab responsiveness, indicating potential for noninvasive monitoring of therapy. Multimodal MR functional imaging thus provides a sensitive and specific tool for tumor grading and evaluation of targeted therapeutic response.