Pakistan journal of pharmaceutical sciences最新文献

Mesenchymal stem cells (MSCs) are applied to clinical practice. Nanometer titanium dioxide (Nano-TiO2) is a type of biological material with great biocompatibility. Herein, we aimed to explore Nano-TiO₂'s effects on differentiation of bone marrow MSCs (BMSCs) after transfection with CXCR4. After transfection of CXCR4 to BMSCs, we cultured BMSCs in medium containing 70 nm and 100 nm Nano-TiO₂. At the same time, BMSCs without CXCR4 transfection were cultured using 100nm Nano-TiO₂ medium and set as NC group. Then the cytotoxicity was detected by MTT assay, followed by ALP staining. Western blot and RT-qPCR were conducted to determine Runx2 and BGP expression. Application of TiO₂ (70 nm and 100 nm) decreased the viability of BMSCs (P < 0.05) and ALP activity, while ALP activity of 70 nm group was markedly greater than that of 100 nm group. After BMSCs were cultured for 7 d and 14 d, lower expression of Runx2 and BGP was noticed in BMSCs of 100 nm group relative to 70 nm group (P < 0.05), accompanied with lower CXCR4 mRNA expression. In conclusion, Nano-TiO₂ exhibited inhibitory effects on CXCR4-transfected BMSCs in a participle size-dependent manner. Increased size of nanoparticles was associated with decreased viability and greater cytotoxicity.

After the occurrence of cerebral hemorrhage (CH), patients generally develop neurological disorders and dysphagia, requiring enteral nutrition support. In this study, the research team explored the impact of predictive management-assisted probiotic low-fat nutritional supplements on CH patients. A total of 114 CH patients admitted to our hospital from August 2022 to June 2024 were selected as the study subjects. They were divided into a control group (n=57) using low-fat nutritional supplements and an experimental group (n=57) using probiotic combined with low-fat nutritional supplements. After treatment, the NIHSS of the experimental group was found to be lower than that of the control group, while the ADL was higher than that of the control group (p<0.05). In addition, glutamate (Glu), aspartic acid (Asp), CD8+ and inflammatory factors were lower in the experimental group than in the control group after treatment, whereas glycine (Gly), gamma-aminobutyric acid (GABA), cluster of differentiation (CD)3+, CD4+, CD4+/CD8+ were higher than in the control group (P< 0.05). In conclusion, probiotic low-fat nutrition combined with predictive management significantly improves neurological function.

The current work aims to study the anti-hyperlipidemic effectiveness of the ethanolic extracts from various parts of Ziziphus spina-christi (Sidr) plant; seed (SSF), pulp (SPF) and leaf (SLF) against rosuvastatin (ROF), 10 mg/kg) in rats induced with hyperlipidemia via a (10-week) high-fat diet. Several biochemical, hematological and physiological parameters were determined. The SSF verified greater effectiveness, mainly enhancing liver and kidney functions in particular; it reduced alanine aminotransferase (ALT) levels to 29.16 U/L (vs. 35.89 in SLF and 29.14 in control) and considerably improved kidney functions by reducing urea and creatinine levels to 1.84 mmol/L and 119.83 µmol/L, respectively. Lipid profile with the SSF group was comparable to the rosuvastatin group. Additionally, SSF group ameliorated the hematological alterations and decreased hyperlipidemia-induced organ damage more than the other extracts. In conclusion, the seed extract was the most efficient part, as it established the most positive function biomarkers, such as ALT activity, urea and creatinine, sustaining its potential for more preclinical and clinical developments.

In this study, we synthesized aryl-substituted tetracarboxylic acid dianhydride (TCDA) diastereomers having potential for chemoselective DNA alkylation. The TCDAs were obtained through a radical-initiated addition chain reaction. Diastereomeric reaction mixture was characterized by FTIR, UV, EI-MS, and elemental analysis. Quantum Mechanical (QM) calculations, including relaxed potential energy surface (PES) scans at B3LYP/6311+G (d,p) and MP2/6-31G optimizations of global minima of each diastereomer, revealed that the most stable and polar aryl-substituted TCDA diastereomers adopt non-anti dihedral geometries between the two anhydride rings. This conformation effectively reduces nucleophilic accessibility on the C=O, thereby limiting nucleophilic attack under physiological conditions, with possible activation under mildly acidic microenvironments of tumors. The stability and polarity are additional helpful drug attributes. Further validation of reduced reactivity came from biological screening of the aryl-substituted diastereomeric mixture against human HeLa cancer cell line, which demonstrated reduced reactivity compared to alkyl TCDA control analogs, despite both sharing the same crosslinking TCDA arm. These computational and bioactivity results suggest that aryl substitution imposes conformational constraints that induce environment-dependent differences in reactivity. Overall, this study shows that stereoelectronic factors can modulate reactivity, offering a rationale for the development of selective therapeutic agents. Further investigations are underway to evaluate the individual bioactivities of isolated diastereomers.

The therapeutic approach of combining doxycycline (DOX) with azithromycin (AZM) has emerged as an effective strategy for managing pediatric Mycoplasmal pneumonia (MP), with its clinical efficacy well-established. It is worth noting that both DOX and AZM are antibiotics and require an interval of 24-72 hours when used in combination, but there are few studies on the optimal interval between the two drugs. This study aimed to elucidate the differential outcomes of two treatment regimens. The short-term group received DOX in combination with AZM within 24-72 hours after AZM administration for MP treatment, while the long-term group initiated DOX therapy more than 72 hours after AZM treatment. Our findings indicated that there were no statistically significant differences in clinical efficacy and the impact on pediatric pulmonary function between the two groups (P>0.05). However, the time for symptom improvement in the short-term group was significantly shortened (P<0.05), while the long-term group exhibited lower inflammatory responses, stress responses and a reduced incidence of complications (P<0.05). In conclusion, initiating DOX within 72 hours after AZM treatment can expedite the treatment course of MP, while using DOX more than 72 hours after AZM treatment confers enhanced safety.

Older leukemia patients frequently endure cancer-related pain and fatigue, impairing their daily lives and reducing treatment adherence. Pharmacological intervention is a key approach to alleviating these symptoms. This study focuses on the efficacy and safety of analgesic and anti-fatigue drugs in elderly leukemia patients, aiming to optimize drug selection for precision treatment. From January 2022 to June 2024, Taixing People's Hospital enrolled 82 elderly leukemia patients with pain and fatigue, dividing them into a control group (no analgesics) and a celecoxib group. Clinical outcomes: Pain relief, fatigue reduction, depression improvement, quality of life and adverse reactions were compared at 1, 4, and 8 weeks. The celecoxib group showed significant improvements in pain, fatigue, anxiety, and depression, with better scores on the Numeric Rating Scale (NRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Edmonton Symptom Assessment System-revised (ESAS-r), the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and the Hospital Anxiety and Depression Scale-Depression (HADS-D) scales at all-time points (P<0.05). Their Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL) scores also indicated enhanced functional and overall quality of life, with lower symptom scores compared to the control group (P<0.05). No serious adverse events occurred, confirming celecoxib's safety.

Granulomatous mastitis (GM) is a chronic inflammatory breast disease with a high recurrence rate and low effectiveness of the traditional treatments. This randomized controlled trial compared the effectiveness of the combined use of Xihuang Capsules and low-power High-Intensity Focused Ultrasound (HIFU) and their impact on macrophage infiltration (CD68) and cell proliferation (Ki67). Sixty women with histologically proven GM were randomized to experimental (HIFU + Xihuang) or control (HIFU alone) groups (n=30 each group). Follow-up was for 12 weeks and recurrence at 6 months. Compared with controls, the combination group experienced more lesion reduction (3.50±0.79 cm to 0.92±0.42 cm vs. 3.42±0.88 cm to 1.85±0.60 cm, p<0.001), improved complete resolution (86.7% vs. 60.0%, p = 0.023), earlier resolution (6.2±1.4 vs. 9.1±1.8 weeks, p<0.001) and greater pain reduction (VAS: 7.2±1.1 to 1.3±0.6 vs. 7.0±1.3 to 2.8±0.9, p<0.001). Immunohistochemistry also demonstrated marked reductions in CD68+ macrophages and Ki67 index, both blindly graded. Recurrence at 6 months reduced with combination therapy (6.7% vs. 20.0%, p=0.098). Both treatments were well tolerated. These data indicate that Xihuang Capsules plus low-power HIFU produce faster regression of lesions, disappearance of symptoms and modulation of macrophage infiltration and cell proliferation in GM, with tendency of decreased recurrence.

Glomerulonephritis (GN) is a kidney disorder characterized by inflammation of the glomeruli. This study aims to explore the potential therapeutic mechanisms of C. officinalis in the treatment of GN through network pharmacology and molecular docking analysis. The active ingredients of the plant were obtained from the intersections of articles and databases. The GN targets were obtained from the GeneCards database. The STRING database was used to construct a PPI network obtained from the intersection of target and disease. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the biological significance of disease and plant active ingredient targets. Quercetin, isorhamnetin and kaempferol were identified as key compounds, while TNF, AKT1 and SRC emerged as central targets in the PPI network. GO and KEGG analyses revealed that C. officinalis may exert its effects through processes on important signaling pathways including PI3K-Akt and EGFR tyrosine kinase inhibitor resistance. Molecular docking results provided important affinities between the main compounds and the core proteins. This study provides a preliminary scientific foundation for future investigations into the molecular mechanisms by which C. officinalis may contribute to the treatment of glomerulonephritis.

This study investigated the effects of Proton pump inhibitors (PPIs) combined with triple therapy on elderly non-erosive gastroesophageal reflux disease (NERD) patients. A total of 120 elderly patients diagnosed with NERD were divided into two groups: The study group received PPIs combined with triple therapy, while the control group received PPI monotherapy. Significant improvements were observed in the study group compared with the control group: gut microbiota diversity (Shannon Index: from 3.80±0.40 to 5.30±0.60), increased abundance of beneficial Lactobacillus and Bifidobacterium and reduced Enterococcus levels (All p<0.001). Visceral hypersensitivity scores showed increased pressure and pain thresholds (p<0.001) and reduced urgency and bloating (p<0.05). Gastrointestinal hormone such as motilin, ghrelin levels were increased (both p<0.001), and somatostatin was decreased (p=0.034). Systemic inflammatory markers such as IL-6, CRP, TNF-α, and IL-1β significantly declined, while anti-inflammatory IL-10 increased (All p<0.001). GERDQ scores improved more significantly in the study group (p < 0.001), and SF-36 quality of life domains reflected better physical and mental outcomes (p<0.001). These findings underscore the potential of combination therapy as a superior treatment strategy for elderly NERD patients, improving both clinical outcomes and quality of life. Further studies are warranted to explore long-term benefits and optimize treatment protocols.

The clinical and microbiological features of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia among intensive care unit (ICU) patients were assessed in this study, as well as the relationship between linezolid treatment and outcomes. Of 282 ICU patients (January 2019-March 2024), 176 survived and 106 passed away. Independent predictors of death were age >60 years, tracheal intubation, central venous catheterization, ≥3 comorbidities and elevated procalcitonin (PCT). Seventy-two sputum representative MRSA isolates were analyzed for resistance determinants (mecA, SCCmec) and prevalent virulence genes (sea, hla,tsst-1,icaA,pvl). Linezolid therapy was associated with improved survival, reduced PCT levels and reduced prevalence of sea, tsst-1 and icaA. pvl co-presence with other virulence genes was related to poor outcomes. Including use of linezolid in predictive models improved discrimination (ROC AUC 0.805) .Transfusion recipients frequently present with independent risk factors associated with mortality in ICU patients diagnosed with MRSA pneumonia. Prognosis for ICU MRSA pneumonia is based on clinical risk factors, virulence gene carriage and transfusion status. Limitations are the retrospective study design and that sputum samples were used, which may result in misclassification.