There are fifteen species of Datura, a perennial shrub-like herb, with Datura alba (D. alba) being the most important medicinal plant because of its therapeutic and aesthetic uses. Pharmaceutical goods use fresh seeds, fresh leaves, roots, dried leaves, dried mature seeds and fruits of D. alba. Seed proteins are the plant component most often overlooked for use in complementary and alternative medicine, even though all plant parts have nearly identical therapeutic properties and effects. This results from a deficiency of knowledge on the components of proteins. The current study is to extract proteins from D. alba plant seeds in order to show data that will identify few major enzymes in the whole protein extract. The protein chemistry techniques, such as gel electrophoresis and chromatography, have been applied for seed protein analysis. After extraction of seed proteins in PBS (pH 7.4) buffer, the chromatography using DEAE Sephacryl (macroprep) resin, SDS-PAGE, zymography and biochemical tests were performed. There were three distinct peaks identified by the chromatographic separation. Protein bands were visible in the reduced and non-reduced SDS-PAGE analysis, while the results of substrate zymography indicated the presence of proteases and phospholipases. Strong antioxidant activity and antibiofilm activity on MRSA were also observed in the D. alba seeds proteins. Enzymatic and biochemical activities were observed with the protein extract obtained from the seeds of D. alba. Fractions of the proteins were also active and showed separation of protein components on the basis of ionic strength.
Evidence from experimental and clinical studies suggests that anesthetic drugs may modulate tumor biology by influencing immune regulation, inflammation and intracellular calcium signaling. However, the extent to which sevoflurane or propofol alters calcium-related molecular expression in human breast cancer tissue remains unclear. This study aimed to compare the effects of sevoflurane- versus propofol-based anesthesia on calcium signaling pathway-related gene and protein expression in breast cancer tissues and to evaluate their association with early -postoperative recovery and short-term oncologic outcomes. A total of 38 female patients undergoing breast cancer surgery were prospectively randomized to the sevoflurane group (S group, n=19) or the propofol group (P group, n=19). Paired tumor and adjacent normal tissues were collected intra-operatively. mRNA expression of RYR2 and CALML5 was quantified using RT-qPCR and protein levels were assessed by Western blotting. Postoperative pain was evaluated using the 24-hour resting numerical rating scale (NRS), recovery quality using the quality of recovery-15 (QoR-15) on post-operative day 1 and incision pain at post-operative months 3 and 6. Tumor recurrence or metastasis was monitored for 6 months. Compared with the propofol group, sevoflurane anesthesia demonstrated a nonsignificant upward trend in RYR2 mRNA and protein expression (P>0.05), whereas CALML5 expression showed a significant increase under sevoflurane (P<0.001). No significant intergroup differences were detected in 24-hour NRS scores, post-operative QoR-15, chronic incision pain at 3 or 6 months, or 6-month recurrence/metastasis rates (all P>0.05). Sevoflurane anesthesia induced a selective increase in CALML5 expression compared with propofol, suggesting potential differential modulation of calcium-associated molecular pathways. However, these molecular changes did not translate into measurable differences in early recovery, post-operative pain, or short-term oncologic prognosis. The findings support the clinical non-inferiority of sevoflurane compared with propofol and provide preliminary molecular evidence to guide future mechanism-based perioperative investigations.
The interactions of non-steroidal anti-inflammatory drugs (NSAIDs) with excipients significantly influence their solubility, stability and bioavailability, and have a significant impact on the therapeutic efficacy of drugs. The present study explores the molecular interactions between the NSAID and D-mannitol in an aqueous system over the temperature range 293.15 to 313.15 K, using thermo-acoustic and computational techniques. Thermo-acoustic parameters, including apparent and partial molar volume (Øv, Øov), apparent and partial molar isentropic compressibility (Øk, Øok), and transfer partial molar volume (∆tr, Øov), etc, were calculated using experimental data of density (ρ) and sound velocity (u). The positive values of partial molar volume and the negative value of partial molar isentropic compressibility indicate the existence of molecular interactions. The positive values of ∆𝑡𝑟∅𝑣° indicate the existence of ion-hydrophilic and hydrophilic-hydrophilic interactions. Hepler's constant (∂2Øov/∂T2)p indicates that Sodium naproxen (Na-NAP) acts as a structure-maker in the presence of D-mannitol in the aqueous solution. In addition to volumetric and acoustic studies, computational work involving HOMO-LUMO analysis, single-point energy calculations, dipole moments, and global reactivity descriptors highlights the stability and reactivity of the interacting species. In the gas phase, the HOMO-LUMO gap decreased significantly (0.29 eV), but it increased in aqueous medium (2.83 eV), suggesting that the complex has stabilized. These findings offer a strong foundation for stabilizing drugs through structure-making behaviour, providing a rational basis for developing effective pharmaceutical formulations.
Drug resistance phenomenon has become a serious problem in the lipid lowering drugs in the treatment of cardiac and dyslipidemic patients. Statins are the mainstay pharmacological treatment for dyslipidemia, metabolized by CYP3A4 gene. CYP3A4 genetic variants are involved in statins resistance, of which CYP3A4*4 and CYP3A4*1G has been observed as important loss of function alleles. The current study aimed to investigate the CYP3A4 (CYP3A4*4 and CYP3A4*1G) polymorphisms, their association with lipid parameters and influence of variations in response to statin drugs. This cross-sectional observational study included 100 cardiac and dyslipidemic patients receiving statin therapy at Mayo Hospital Lahore, Pakistan. Biochemical assays were performed for lipid parameters and genotyping of CYP3A4 (CYP3A4*4 and CYP3A4*1G) variants by using allele specific polymerase chain reaction (AS-PCR) technique. The amplicons of identified variants were electrophoresed and results were verified through Sanger sequencing. Serum lipid profile of selected patients presented higher values of total cholesterol (TC) in 51% individuals, total triglycerides (TG) in 79%, LDL- cholesterol in 46% and HDL- cholesterol in 17%. Observed genotypes for CYP3A4*4 and CYP3A4*1G in selected patients included homozygous wild type, homozygous mutant type, heterozygous bi- allelic, as well as tri and tetra- allelic patterns representing multi-locus haplotype combinations. Statistical analysis was performed using SPSS version 27.0. Significant correlations were observed between lipid parameters, whereas CYP3A4 variants showed modest associations with lipid parameters in studied population. The study provides significant inter racial genetic variations in CYP3A4*4 and CYP3A4*1G in studied population, which might be responsible for the variable response of statins in cardiac and dyslipidemic patients. Although the study addresses the main question about pharmaco-genetic in studied population, the observed genotype-phenotype associations are limited and should be interpreted carefully, emphasizing on the need for additional validation in larger population.
Current diabetes therapies often fail to address the loss of insulin-producing β-cells. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into insulin-producing cells (IPCs), but functional maturity remains limited. Toll-like receptor 9 (TLR9) agonists may enhance BMSC maturation. To investigate the ability of TLR9 agonists to promote the maturation of BMSCs in diabetic rats. BMSCs were isolated from rat bone marrow and identified by trilineage differentiation tests and flow cytometry. BMSCs were then differentiated into IPCs and treated with different concentrations of TLR9 agonists. PCR detected transcriptional levels of pancreatic endocrine-related genes. Diabetic model in rats was established using streptozotocin. BMSCs were encapsulated in TheraCyte capsules and subcutaneously transplanted into diabetic rats. Intraperitoneal injection of TLR9 agonists was performed, with serum insulin, C-peptide and fasting blood glucose (FBG) levels monitored in the transplanted rats. The recovered BMSCs were further characterized by immunofluorescence staining after the rats were killed. Differentiated BMSCs displayed characteristics of IPCs, such as the ability to secrete insulin and C-peptide in vitro. Further, when exposed to gradient concentrations of TLR9 agonists, differentiated MSCs exhibited enhanced expression of pancreatic-associated endocrine genes and transcription factor levels. In vivo, differentiated BMSC transplantation combined with TLR9 agonist administration notably improved diabetic conditions, as evidenced by suppressed FBG levels and elevated serum insulin and C-peptide levels, comparable to those in the normal group. However, withdrawal of TLR9 agonists attenuated the therapeutic effects. Finally, immunofluorescence staining confirmed that a TLR9 agonist promoted IPC maturation, as evidenced by co-expression of insulin and C-peptide in vivo. TLR9 agonists promote the differentiation and functional maturation of BMSCs into IPCs, thereby improving metabolic parameters in diabetic rats. This "stem cell-immunomodulator" strategy provides a foundation for developing functional β-cell replacement therapies.
Chronic deep vein thrombosis (DVT) is a persistent clinical condition that often results in venous obstruction, post-thrombotic syndrome and impaired quality of life. Conventional endovascular dilation is limited by elastic recoil and high rates of restenosis caused by neointimal hyperplasia. Paclitaxel-based localized venous therapy enables targeted delivery of antiproliferative agents directly to the venous wall, offering a pharmacological strategy to suppress pathological vascular remodeling and improve long-term outcomes. To evaluate the efficacy and safety of paclitaxel-based localized venous therapy in improving long-term venous patency and reducing restenosis in patients with chronic DVT, compared with conventional angioplasty. This retrospective multicenter study analyzed patient records from three vascular centers between 2019 and 2024. A total of 245 patients with chronic DVT were included, of whom 127 received paclitaxel-based localized therapy and 118 underwent conventional angioplasty. Primary endpoints were venous patency and restenosis rates. Secondary endpoints included freedom from clinically driven reintervention and quality-of-life outcomes. Clinical and imaging follow-up was conducted at baseline and at 6, 12 and 24 months. Multivariate regression analysis was performed using SPSS version 28. At 24-month follow-up, primary venous patency was significantly higher in the paclitaxel-based therapy group than in the conventional angioplasty group (82.7% vs. 61.9%), with lower restenosis rates (11.8% vs. 29.7%). Paclitaxel-based localized therapy was associated with greater freedom from reintervention (hazard ratio 0.42; 95% CI 0.29-0.61; p < 0.001). Quality-of-life scores improved significantly in the paclitaxel group (mean difference 14.3 points; p = 0.002). No significant differences were observed in major complications or thrombotic events between groups. Paclitaxel-based localized therapy provides superior long-term venous patency, reduced restenosis and improved quality of life without compromising safety. These findings highlight the pharmaceutical relevance of localized antiproliferative drug delivery in the management of chronic venous disease.
Acute non-large-vessel occlusive ischemic stroke (ANLVOIS) is a common subtype of stroke. The core of treatment is to rapidly improve cerebral perfusion and reduce neurological injury. Aspirin is used in the acute phase, but its efficacy is limited in some patients. Tirofiban (a highly selective glycoprotein IIb/IIIa receptor antagonist) is widely used and there are few direct comparative studies of its efficacy and safety with those of the other drugs. To compare the clinical efficacy and safety of the antiplatelet drugs tirofiban and aspirin in the treatment of ANLVOIS. This retrospective controlled study collected clinical data of ANLVOIS patients from Wuqiao County People's Hospital (Jan 2023-Dec 2024), grouped by treatment: Group A (n=55, aspirin alone) and Group B (n=58, tirofiban bridging to aspirin). NIHSS scores (pre-treatment, 1 week, and 3 months post-treatment) were analyzed for neurological function, and 3-month mRS scores were analyzed for prognosis. 90-day all-cause mortality, symptomatic intracranial hemorrhage (sICH) incidence and adverse event rate were compared. Statistical analyses were performed using SPSS 26.0. Baseline characteristics were balanced between the two groups (P>0.05). At 7 days and 3 months post-treatment, NIHSS and mRS scores decreased significantly in both groups (P<0.05), with Group B having notably lower scores than Group A (P<0.05). The 90-day all-cause mortality, sICH incidence and adverse event rates were 1.7%, 3.4%, and 6.9% in Group B, respectively, compared with 3.6%, 5.5%, and 16.4% in Group A, with no significant intergroup differences (P>0.05). In this retrospective analysis, early treatment with tirofiban followed by aspirin was associated with better neurological and functional outcomes in ANLVOIS than aspirin alone, while maintaining a comparable safety profile. These real-world findings support the use of tirofiban-based induction as an effective acute-phase antiplatelet strategy.
Streptococcus suis (S. suis) is a significant zoonotic pathogen, with serotype 2 (SS2) being the most prevalent. Suilysin (SLY), an essential toxin indicator for S. suis, is crucial in the infections caused by SS2. Consequently, an anti-virulence strategy targeting SLY presents a promising approach to combat SS2. To investigate the effect of curcumin, a naturally occurring phenolic compound, on the hemolytic activity of SLY and the pathogenicity of SS2, and to assess its viability as a novel anti-virulence candidate for addressing SS2 infections. The antibacterial activity of curcumin against SS2 was assessed by determining its minimal inhibitory concentration (MIC) and monitoring bacterial growth curves. Its impact on hemolytic activity was tested using supernatants from SS2 cultures and purified recombinant SLY protein. Western blot was used to determine if curcumin affected the secretion level of SLY. The interaction between curcumin and SLY was predicted using molecular docking. Finally, the protective efficacy of curcumin was evaluated in a murine model of lethal SS2 infection. Curcumin (<1,024 μg/mL) did not inhibit SS2 growth or viability. However, it significantly and dose-dependently inhibited the hemolytic activity of both SS2 culture supernatants and purified SLY. Molecular docking predictions indicated that curcumin engaged three domains of SLY (D1, D2 and D3) simultaneously, forming five hydrogen bonds with residues ASN-50, GLN-107 and LYS-190, thereby supporting its multidomain-binding capability. Furthermore, curcumin administration significantly reduced the mortality of SS2-infected mice in vivo. Substantial evidence is presented demonstrating that the pathogenicity of SS2 can be effectively attenuated by curcumin via inhibition of the hemolytic activity of SLY, which supports the potential utility of curcumin as a host-directed anti-virulence agent for SS2 infections.
Neurological worsening after hospital admission frequently correlates with poor clinical prognosis. However, treatment options are limited for acute ischemic stroke patients who are outside the thrombolytic time window and do not have large vessel occlusion (LVO). This study evaluated the safety and efficacy of intravenous tirofiban in this population. A total of 44 patients diagnosed with progressive ischemic stroke were analyzed, defined as an increase of ≥2 points on the NIHSS or a ≥1-point worsening in limb motor score within 24 hours of symptom onset. of these, 26 received intravenous tirofiban in addition to dual antiplatelet therapy, while the remaining 18 received dual antiplatelet therapy alone. The primary efficacy endpoints were the NIHSS score at 7 days and the proportion of patients achieving a superior functional outcome [modified Rankin Scale (mRS) score 0-1] at 3 months. Symptomatic intracranial hemorrhage, systemic bleeding events and thrombocytopenia were monitored. The tirofiban group showed greater neurological improvement at 7 days (p < 0.001) and an increased favorable outcome at 90 days (80.77% vs 27.78%, p = 0.001). Logistic regression confirmed tirofiban as an independent parameter of favorable outcome (adjusted OR 15.67, 95% CI: 2.97-82.61, p = 0.001). Neither group presented symptomatic intracranial hemorrhage, systemic bleeding, or thrombocytopenia. Intravenous tirofiban may represent a potential therapeutic option for patients with progressive ischemic stroke beyond the thrombolytic window and without LVO, showing an association with improved neurological recovery and functional outcomes. Its clinical efficacy and safety shall be further confirmed through large-scale, randomized, prospective studies.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and currently lacks defined therapeutic targets. Although miR-152-3p functions as a tumor suppressor in various cancers, its specific mechanism and regulatory network in TNBC remain poorly understood. To investigate the expression and tumor-suppressive function of miR-152-3p in TNBC cells and to elucidate its mechanism of targeting STAT3, RELA and ADCY6. miR-152-3p expression was compared between MDA-MB-231 and MCF-10A cells using qRT-PCR. MDA-MB-231 cells were transfected with miR-152-3p mimics or inhibitors and cell proliferation, apoptosis and invasion were assessed by MTT assay, flow cytometry and Transwell assay, respectively. Direct target interactions were validated by a dual-luciferase reporter assay, and protein levels of STAT3, RELA, and ADCY6 were examined by Western blot. Key findings were further validated in Hs 578T cells. miR-152-3p expression was significantly downregulated in TNBC cells. Overexpression of miR-152-3p markedly inhibited proliferation and invasion while promoting apoptosis in MDA-MB-231 cells. Dual-luciferase reporter assays confirmed that miR-152-3p directly binds to the 3'untranslated regions of STAT3, RELA and ADCY6. Overexpression of miR-152-3p significantly reduced STAT3 and RELA protein levels while upregulating ADCY6 expression. Rescue experiments demonstrated that restoration of STAT3 expression partially reversed the tumor-suppressive effects of miR-152-3p. These findings were recapitulated in Hs 578T cells, suggesting generalizability across TNBC subtypes. miR-152-3p suppresses TNBC progression by downregulating STAT3/RELA and upregulating ADCY6, thereby activating cAMP signaling. These findings provide a foundation for further investigation into the potential of miR-152-3p as a multi-target therapeutic strategy for TNBC.
Liver cancer is a leading cause of cancer-related mortality worldwide. Clinical use of the first-line drug sorafenib is limited due to drug resistance and severe adverse effects. The current study aimed to synthesize a series of N-arylated thiophene-based 1,3,4-oxadiazole derivatives containing a carbamothioate moiety (7a-7d) as potential anticancer agents with improved efficacy and safety profiles. Derivatives were synthesized via coupling of thiophene-based 1,3,4-oxadiazole (compound 1) with various electrophiles, yielding 62-86%. The structures of all derivatives were established based on FT-IR, 1H NMR, 13C NMR, and EI-MS. The in-vitro anticancer effect of all derivatives was assessed using the MTT assay against the HepG2 cancer cell line and their hemolytic safety was assessed on human red blood cells. All derivatives exhibited cytotoxicity with minimal hemolytic effects. Derivative 7b (2,6-dimethyl) exhibited excellent activity by reducing cell viability of 33.96 ± 2.47% at 100 μg/mL and minimal hemolysis (1.20 ± 0.01%) with a high selectivity index (SI) of 28.3, similar to sorafenib (34.32 ± 1.91%, SI = 27.45). Derivatives 7a (phenyl) and 7d (ethyl) showed moderate activity and 7c (fluoro) was the least potent. Thiophene-based oxadiazole-coupled carbamothioate derivatives, particularly 7b, demonstrate enhanced anticancer efficacy and safety compared to sorafenib, representing promising candidates for targeted liver cancer therapy.
Ribosome biogenesis is involved in the progression of hepatocellular carcinoma (HCC), but the specific mechanisms and diagnostic values of ribosome biogenesis-related genes (RBRGs) in HCC remain unclear. We aimed to explore potential therapeutic targets in HCC from RBRGs. The differentially expressed RBRGs (DE-RBRGs) were explored using publicly available bulk RNA-sequencing data. Cox regression analysis was employed to evaluate the prognostic significance of the DE‑RBRGs. The optimal machine learning algorithm was selected to construct a prognostic model. The predictive performance of the model was assessed using Kaplan‑Meier analysis and receiver operating characteristic (ROC) curves. Single‑cell RNA‑sequencing data were subsequently utilized to identify key cell populations and the corresponding DE‑RBRGs. Bioinformatics analyses revealed 88 DE-RBRGs, predominantly enriched in ribosome biogenesis-related functions and pathways. The univariate Cox regression identified 12 DE-RBRGs with prognostic values. Following, the optimal machine learning algorithm (StepCox [forward] + SuperPC) was selected to construct a prognostic model. Survival analysis demonstrated that patients in the low-risk group exhibited markedly prolonged lifespan relative to their high-risk counterparts. ROC curves confirmed the predictive accuracy of this prognostic model in both training and validation cohorts. These 12 DE-RBRGs were significantly associated with immune cell infiltration, tumor immune evasion and drug sensitivity. Analysis of single-cell sequencing data identified hepatocytes as central mediators of HCC pathogenesis, which was associated with high expression of two DE-RBRGs: Nucleophosmin 1 (NPM1) and Ras-Related Nuclear Protein (RAN). NPM1 and RAN, which are highly expressed in hepatocytes, may serve as potential therapeutic targets in HCC. Their established roles in ribosome biogenesis could drive the development of novel therapies targeting this pathway.
CK18-M30 is an emerging biomarker to be used in patients who have liver damage from drugs or other causes and is now commonly used as a marker of liver apoptosis in patients with drug-induced liver damage. To investigate the effects of different storage conditions on the stability of human cytokeratin 18-M30 (CK18-M30) in serum, this study aims to provide data-driven evidence on sample stability for deferred laboratory testing of clinical specimens that cannot be analysed immediately. A total of 22 serum samples from individuals undergoing routine physical examination were collected and had different concentration levels of CK18-M30 in the Fourth Affiliated Hospital, Zhejiang University School. Baseline value from the immediate test. The remaining samples were distributed into five groups. Aliquots stored at -20°C in cryotubes for 3 days and 2-8°C separation gel tube samples for 3 days had >80% concordance with the baseline and were not different (P > 0.05). Conversely, 2-8°C cryotube aliquots stored for 3 or 7 days, as well as 2-8°C separation gel tubes stored for 7 days, had concordance rates below 80%, significantly discrepant from the baseline (P < 0.01). CK18-M30 is relatively stable at -20°C. Between 2 and 8°C, the separation gel tubes were more stable than the aliquot tubes for up to three days. Aliquot tubes stored at 2-8oC were suboptimal, as the CK18-M30 became unstable after 3 days. The demonstrated stability characteristics of serum CK18-M30 are crucial for ensuring trustworthy biomarker-based safety evaluation when immediate analysis is not possible, given its expanding use as a safety and pharmacodynamic biomarker in pharmaceutical research, especially for tracking drug-induced liver injury in clinical trials and pharmacovigilance programs.
Sorafenib (SB) is a receptor tyrosine kinase inhibitor, currently marketed as an oral dosage form. However, due to severe irritation of the gastrointestinal tract, the drug is facing decreased acceptability as a therapeutic agent. This study aimed to develop nano-scaffolds to increase the drug loading capacity and decrease the adverse drug reactions of SB. Polymers used for the preparation of nano-scaffolds were polylactic co-glycolic acid (PLGA), ethyl cellulose (EC) and polyvinyl alcohol which was used as a surfactant. A range of different formulations was designed using 12.5 mg and 25 mg of EC, while the concentration of the PLGA was kept constant throughout the study. All formulations with or without the drug were characterized for size by dynamic light scattering (DLS), scanning electron microscopy, differential scanning calorimetry, hemolysis assay, cell viability assay, apoptotic assay and in-vivo evaluation. DLS results showed the minimum nano-scaffold size of 252.8 ± 12 nm, which was increased by increasing the concentration of polymer and drug. The physicochemical assessment showed the presence of minor interactions between the polymeric system and SB. The cell viability assay showed the minimum cell viability at 50.66 ± 0.13 % at a maximum concentration of SB-loaded formulations, whereas the presence of apoptotic bodies confirmed these results. The in-vitro and in-vivo evaluation showed the safety profile of the polymeric PLGA/EC in the absence of drug content. Therefore, the fabricated system may be used as a carrier system for SB and can further be included in tumor model studies.
Immune checkpoint inhibitors have transformed anticancer pharmacotherapy, with nivolumab demonstrating significant immunomodulatory potential when combined with cytotoxic agents. However, real-world pharmacological evidence regarding the safety, tolerability and biomarker-guided response of neoadjuvant nivolumab combined with platinum-based chemotherapy in resectable non-small cell lung cancer (NSCLC) remains limited. This study aimed to evaluate the pharmacological efficacy, safety profile and predictive biomarker associations of this combination regimen in clinical practice. A multicenter retrospective pharmacological outcome study was conducted in 58 patients with stage IB-IIIB resectable NSCLC who received four cycles of neoadjuvant nivolumab in combination with platinum-based chemotherapy. The primary pharmacodynamic endpoint was major pathological response (MPR), serving as a surrogate marker of drug efficacy. Secondary endpoints included pathological complete response (pCR), treatment completion rate, post-treatment surgical resectability and incidence of adverse drug reactions graded according to CTCAE v5.0. Programmed death-ligand 1 (PD-L1) expression and KRAS mutation status were evaluated as predictive biomarkers of drug response. The median patient age was 60 years, with male predominance (70.7%). Adenocarcinoma was the most prevalent histological subtype (60.3%). High PD-L1 expression (≥50%) was observed in 31.5% of patients, while KRAS mutations were detected in 44.8%. Curative surgical resection was achieved in 77.6% of patients following neoadjuvant pharmacotherapy. MPR and pCR rates were 43.1% and 29.3%, respectively, with significantly higher response rates observed in patients exhibiting elevated PD-L1 expression. Grade ≥3 adverse drug reactions occurred in 17.2% of patients, with no treatment-related mortality, indicating an acceptable safety and tolerability profile. Neoadjuvant nivolumab combined with platinum-based chemotherapy demonstrates favorable pharmacological efficacy, manageable toxicity and biomarker-driven therapeutic response in resectable NSCLC under real-world clinical conditions. These findings support the role of personalized immunopharmacotherapy and reinforce the clinical relevance of biomarker-guided drug selection in modern pharmaceutical oncology.
The effective management of third-degree burns remains challenging due to high risks of infection, oxidative stress and prolonged inflammation. While several medicinal plants are traditionally used in wound care, scientific evidence supporting their efficacy is often lacking. This study aimed to evaluate the therapeutic effect of an ointment formulated with the ethanolic extract of Lawsonia inermis leaves on the healing of severe burns. Twenty-one adult male Wistar rats were randomly assigned to three groups: Negative control, positive control (standard drug) and test group (L. inermis). Standardized third-degree burns (200°C for 10 seconds) were induced on the animals' backs and treated topically for 27 days. Wound contraction was monitored throughout the study and histological analysis was conducted at the end. Additionally, phytochemical screening and in-vitro assays were performed to assess the antioxidant (DPPH, FRAP and FIC), anti-inflammatory and antibacterial activities of the extract. The results demonstrated that Lawsonia inermis exhibits significant antioxidant, anti-inflammatory and antimicrobial activities. Furthermore, its topical application promoted wound healing in a manner comparable to conventional treatments. These findings highlight the therapeutic potential of L. inermis as a promising natural alternative for the management of severe burn wounds.
Spontaneous abortion and fetal death represent significant reproductive health challenges, affecting approximately 10-20% of recognized pregnancies. Certain medications are an acquired risk factor for spontaneous abortion or fetal death. This pharmacovigilance investigation sought to systematically assess the disproportionality signal of medication-associated spontaneous abortion or fetal death by leveraging the most extensive publicly accessible database of adverse event reports. Reports from the FDA Adverse Event Reporting System (FAERS) were used to conduct disproportionality analysis, ranging from the first quarter of 2004 to the second quarter of 2025. Medications were categorized based on the Anatomical Therapeutic Chemical (ATC) classification system. The analysis identified 43,199 reports of drug-related spontaneous abortion or fetal death, involving 1,001 different drugs. 119 drugs were identified as significantly associated with disproportionality by the disproportionality analysis. The largest therapeutic category was anti-infective for systemic use (J), comprising 41 drugs (34.5%). Following this were the genitourinary system and sex hormones (G), which had 22 drugs (18.5%), the nervous system (N) with 15 drugs (12.6%), the alimentary tract and metabolism (A) with 9 drugs (7.6%) and antineoplastic and immunomodulating agents (L) with 8 drugs (6.7%). A total of 119 medications were identified as potentially associated with spontaneous abortion or fetal death. This study emphasizes the elevated disproportionality signal associated with anti-infectives for systemic use, as well as the genitourinary system and sex hormones. Identification of specific medications linked to these adverse outcomes can guide targeted medication counseling for women planning pregnancy.
Piperine, one of the alkaloid compounds from Piper nigrum L., has been renowned for its remarkable pharmacological effects, including its antihyperlipidemic activity. However, piperine exhibits poor solubility and impairs pharmacological effectiveness. The aim of the study was to develop piperine-succinic acid nano-cocrystals and to investigate their efficacy in reducing serum cholesterol and triglyceride levels in male Wistar rats. Nano-cocrystals were prepared by the wet milling method and characterized for solid-state properties. Antihyperlipidemic activity was tested in 24 rats, which were randomly assigned into four groups: negative control group (NaCMC 0.5%), positive control group (simvastatin 0.18 mg/kgBW), intact piperine group and nano-cocrystals piperine-succinic acid group with a dose equivalent to 40 mg/kg of the body weight. Serum total cholesterol and triglyceride levels were measured enzymatically. Thermal and X-ray diffraction analyses confirmed the formation of new crystalline structures. The average particle size was 245.5 nm with a polydispersity index of 0.447 and a zeta potential value of -2.51 mV, indicating limited colloidal stability. Despite this, the nano-cocrystals significantly reduced total cholesterol and triglyceride levels compared to intact piperine (p<0.05). The duration of treatment also influenced lipid reduction (p<0.05). Although the formulation demonstrated enhanced bioactivity, further optimization of stability parameters is warranted to ensure long-term efficacy.
Caesalpinia bonducella (CB) leaves, exhibiting diversified remedial impact, offering a wide range of restorative benefits, still need scientific validation due to the scarcity of reported information using in-vivo, multi-solvent-based strategies (Aqueous, Methanol, Acetone) for thorough phytochemical analysis on hepatoxicity model. As oxidative stress underlies hepatic deterioration, scientific investigations are increasingly turning to natural alternatives, especially phytochemical-based antioxidants, for the restoration of liver pathologies. The current investigation was undertaken to explore the restorative potential of CB leaf extracts in CCl4-mediated Hepatotoxicity in rats. Thirty-six male rats, six groups, 40-day CCl4 treatment. Hepatotoxicity was induced with CCl4 (0.8 ml/kg b.w.) twice weekly. The CB leaf extract groups III to V received CCl4 with aqueous, methanolic and acetonic extracts (100mg/kg b.w., daily) respectively; however, group VI received Silymarin (25mg/kg b.w., daily). The principal biomarkers investigated included liver enzymes (ALT, AST, ALP, GGT), enzymatic antioxidants (catalase, SOD, GSH), lipid peroxidation markers (MDA, 4-HNE, 8-isoprostane), protein oxidation (carbonyls) and DNA damage indicators (8-oHdG, BPDE-DNA adducts). Histological evaluation was conducted to determine the extent of liver damage. The acetonic extract group showed a significant reduction in AST and ALT levels, whereas the aqueous group showed comparable results for ALP and γ-GT levels. Methanolic, acetonic and aqueous extracts restored Catalase, SOD, GSH levels. The MDA and 4-HNE levels were significantly decreased in the acetonic extract group, whereas the methanolic extract group showed the significant reduction in 8-isoprostane levels compared with the CCl4-treated group. Notably, this study is the first to report modulation of protein carbonyl, 8-oHdG and BPDE-DNA adducts by CB leaf extracts. Collectively, these findings highlight the hepatoprotective and antioxidant efficacy of Caesalpinia bonducella leaf extracts, with solvent-specific yet complementary mechanisms that mitigate hepatic oxidative stress, supporting their potential as natural hepatoprotective agents.
Gout is a common form of inflammatory arthritis. This study aimed to explore the mechanism of Erding granules in gout. The anti-gout components and targets of Erding granules were identified using network pharmacology. Molecular docking predicted the degree of binding between compounds and targets. Cell experiments confirmed changes in target expression levels and preliminary anti-inflammatory effects. Erding granules contain 14 potential active ingredients and 18 possible targets for fighting gout. Using KEGG and GO enrichment analyses, two signaling pathways were identified, namely PI3K/AKT and MAPK. Two cellular components, GO: 0035866, alpha-beta3 integrin-PKCalpha complex and GO: 0035867, alpha-beta3 integrin-IGF-1-IGF1R complex, were identified. The key signaling pathways and two cellular components were traced to identify the corresponding genes and experiments were designed to verify them. Through RT-qPCR, it was found that monosodium urate (MSU) can cause increases in the expression levels of INSR, PRKCA and IGF1R mRNA; however, Erding granules can reverse these increases. Under the action of Erding granules, the increased release of IL-1β and IL-18 induced by MSU was reversed. Erding granules may alleviate gout by reducing the release of pro-inflammatory factors via targeting INSR, PRKCA and IGF1R.