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Activity of Ethanol Extract of Songga Wood (Strychnos lucida) as an Antimicrobial and Antibiofilm Agent Against Bacillus species, Salmonella typhi and Candida albicans

Pak J Biol Sci. 2026 Jan;29(1):24-32. doi: 10.3923/pjbs.2026.24.32.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; The extensive use of antibiotics has created selective pressure leading to antimicrobial resistance, with biofilm formation serving as a major defense mechanism. Nearly 80% of infections involve biofilm-producing microorganisms that conventional antibiotics fail to eradicate. This study aimed to evaluate the antimicrobial and antibiofilm properties of ethanol extract from songga wood (&lt;i&gt;Strychnos lucida&lt;/i&gt;) against &lt;i&gt;Bacillus&lt;/i&gt; sp., &lt;i&gt;Salmonella typhi&lt;/i&gt; and &lt;i&gt;Candida albicans&lt;/i&gt;. &lt;b&gt;Materials and Methods:&lt;/b&gt; Antimicrobial and antibiofilm activities of &lt;i&gt;S. lucida&lt;/i&gt; ethanol extract were assessed using the microdilution assay at graded concentrations (0.0625-1%). Biofilm inhibition was examined during both intermediate and maturation phases. Statistical analysis was performed to determine significance (p<0.05). &lt;b&gt;Results:&lt;/b&gt; At the highest tested concentration (1%), the extract demonstrated strong antimicrobial activity, inhibiting 83.89% of &lt;i&gt;Bacillus&lt;/i&gt; sp., 80.03% of &lt;i&gt;S. typhi&lt;/i&gt; and 82.43% of &lt;i&gt;C. albicans&lt;/i&gt;. Pronounced antibiofilm activity was also observed, with inhibition rates of 75.36, 75.58 and 71.82% during the intermediate phase and 61.16, 61.76 and 61.14% during the maturation phase, respectively (p<0.05). &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Strychnos lucida&lt;/i&gt; ethanol extract exhibited significant antimicrobial and antibiofilm effects, indicating its potential as a natural candidate for developing alternative therapeutic agents. Further studies on its active compounds and mechanisms are warranted to support clinical applications.

PMID:41622957 | DOI:10.3923/pjbs.2026.24.32

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Salvadora persica (Miswak) Extract as a Natural Therapeutic Agent for Oral Squamous Cell Carcinoma: in vitro and in silico Evaluation

Pak J Biol Sci. 2026 Jan;29(1):10-23. doi: 10.3923/pjbs.2026.10.23.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; Oral Squamous Cell Carcinoma (OSCC), particularly tongue malignancies, remains a major global health concern due to late diagnosis and limited treatment options. &lt;i&gt;Salvadora persica&lt;/i&gt; (Miswak), traditionally used by ancient Arabs for oral hygiene, contains numerous bioactive compounds with potential therapeutic value. This study aimed to evaluate the antioxidant properties of Miswak extract using different solvents, quantify its total phenolic and flavonoid content and assess its anticancer activity against an oral cancer cell line through &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in silico &lt;/i&gt;approaches. &lt;b&gt;Materials and Methods:&lt;/b&gt; Miswak extracts were prepared using water, acetone and ethanol to compare antioxidant capacity and phytochemical content. The extract exhibiting the highest activity was selected for further analysis. The ethanolic extract was subsequently tested on the human tongue carcinoma cell line (HNO97) using the Sulforhodamine B (SRB) assay to determine cytotoxicity. The ELISA was conducted to quantify TNF-α and VEGF-A levels, while real-time PCR was used to measure the expression of caspase-3 and caspase-7. Molecular docking was performed to evaluate the binding affinity of Miswak-derived compounds toward DAPK1, a key protein involved in regulating apoptosis. Statistical analyses were applied to assess the significance of the findings. &lt;b&gt;Results:&lt;/b&gt; The ethanolic extract exhibited the highest antioxidant activity and was selected for anticancer evaluation. SRB assay results showed potent cytotoxicity against HNO97 cells with an IC&lt;sub&gt;50&lt;/sub&gt; of 260.03 μg/mL. The ELISA confirmed significant downregulation of TNF-α and VEGF-A, indicating pronounced anti-inflammatory and anti-angiogenic effects. Real-time PCR demonstrated upregulation of caspase-3 and caspase-7, suggesting activation of apoptotic pathways. Molecular docking supported these observations by revealing strong binding affinities of the extract’s bioactive compounds to DAPK1. &lt;b&gt;Conclusion:&lt;/b&gt; The ethanolic extract of &lt;i&gt;Salvadora persica&lt;/i&gt; demonstrates promising antioxidant, anti-inflammatory, anti-angiogenic and pro-apoptotic properties, indicating its potential as a natural therapeutic candidate for oral squamous cell carcinoma. These findings provide a strong foundation for further &lt;i&gt;in vivo&lt;/i&gt; and preclinical studies to validate its efficacy and safety.

PMID:41622956 | DOI:10.3923/pjbs.2026.10.23

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Integration of FAM19A5 Expression, Plasma Atherogenic Index and Coronary Artery Histopathology in Diet-Induced Obese Rats

Pak J Biol Sci. 2026 Jan;29(1):1-9. doi: 10.3923/pjbs.2026.1.9.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; Subclinical atherosclerosis in obesity is often not detected early. The FAM19A5 is a novel adipokin that is atheroprotective, known to play a role in inhibiting the proliferation and migration of Vascular Smooth Muscle Cells (VSMC), but its expression in adipose tissue and its association with vascular lesions remain unclear. The Plasma Atherogenic Index (PAI) is also a predictive indicator of cardiovascular risk, but its association with coronary histopathological changes has not been widely evaluated experimentally. The study assesses the relationship between FAM19A5 levels and expression, as well as PAI values, with the histopathological picture of coronary arteries in the obesity model Rattus induced by a high-fat and high-fructose diet. &lt;b&gt;Materials and Methods:&lt;/b&gt; Fourteen male Sprague Dawley rats were divided into a control group (standard feed) and an obesity group (a high-fat and high-fructose diet for 12 weeks). An examination of FAM19A5 levels (ELISA), expression of mRNA FAM19A5 in adipose tissue (qRT-PCR), plasma lipid levels, PAI calculations and histopathological examination of coronary arteries. All analyses were conducted using SPSS version 25 and a p-value<0.05 was considered statistically significant. &lt;b&gt;Results:&lt;/b&gt; Circulating FAM19A5 levels were slightly higher in the obese group than in the control group, but not statistically significant. The expression of mRNA FAM19A5 is not detected in adipose tissue. The PAI value was higher in the obesity group. There was a significant difference in FAM19A5 levels in circulation between groups of coronary artery histopathological scores (p<0.05). The diet model successfully induces multistratified atherosclerotic lesions without additional proinflammatory substances. &lt;b&gt;Conclusion:&lt;/b&gt; The integration of FAM19A5 levels, PAI values and the histopathological picture of coronary arteries provides a preliminary understanding of the progression of subclinical atherosclerosis in obesity. The findings of undetected FAM19A5 mRNA expression support the hypothesis that FAM19A5 is not the primary adipokine and that its role in atherosclerosis is likely systemic or compensatory in nature.

PMID:41622955 | DOI:10.3923/pjbs.2026.1.9

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Expression Characteristics and Prognostic Study of PPP1R13L in Brain Metastases 
of Lung Adenocarcinoma

Zhongguo Fei Ai Za Zhi. 2025 Nov 20;28(11):818-830. doi: 10.3779/j.issn.1009-3419.2025.106.32.

ABSTRACT

BACKGROUND: Lung adenocarcinoma is prone to brain metastasis, and the prognosis of patients is extremely poor. The inhibitor of apoptosis-stimulating protein of p53 (iASPP) protein, encoded by the protein phosphatase 1 regulatory subunit 13-like (PPP1R13L) gene, is a key inhibitor of the p53 pathway and promotes carcinogenesis in various tumors, but its role in brain metastasis of lung adenocarcinoma is unknown. This study aims to analyze the tumor microenvironment characteristics of patients with brain metastasis of lung adenocarcinoma and explore the expression of PPP1R13L in brain metastasis tissues and its clinical significance by single-cell sequencing and clinical sample analysis.

METHODS: Brain tissues from 4 patients with lung adenocarcinoma brain metastasis and 2 patients with oligodendroglioma (ODG) were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2014 to December 2024 for single-cell sequencing. The tumor microenvironment was analyzed by combining single-cell sequencing data from 4 lung adenocarcinoma samples and 4 normal lung tissue samples from public databases. Additionally, clinical data and paraffin sections of 50 patients with lung adenocarcinoma brain metastasis in this hospital were collected, and immunohistochemistry was used to assess iASPP expression and its association with clinicopathologic features and patient outcome.

RESULTS: Compared with the ODG and lung adenocarcinoma groups, the specific epithelial cells in the lung adenocarcinoma brain metastasis group were mainly enriched in oxidative phosphorylation, apoptosis, hypoxia, and p53 pathways. PPP1R13L, as an upregulated differential gene, was highly expressed in the specific epithelial cell subpopulation of the brain metastasis group; the interaction between PPP1R13L-positive cells and fibroblasts was significant, activating cell-matrix adhesion related pathways, with the key ligand-receptor pair being collagen type I alpha 1 chain-cluster of differentiation 44 (COL1A1-CD44). Statistical evaluation revealed that smoking (HR=2.543, 95%CI: 1.159-5.583, P=0.020) and high expression of iASPP (HR=3.351, 95%CI: 1.310-8.575, P=0.012) were independent predictors of poor prognosis in lung adenocarcinoma patients with brain metastases.

CONCLUSIONS: This study revealed the interaction between epithelial cells and fibroblasts in the microenvironment of lung adenocarcinoma brain metastasis and implicate PPP1R13L as a potential prognostic indicator and actionable target, offering rationale for precision therapy against lung adenocarcinoma brain metastases.

PMID:41622929 | DOI:10.3779/j.issn.1009-3419.2025.106.32

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Comparing Cross-Sectional and Longitudinal Study Designs for Accurate Viral Dynamics Estimation: Insights From the NBA Cohort Data

J Med Virol. 2026 Feb;98(2):e70823. doi: 10.1002/jmv.70823.

ABSTRACT

Viral load data provide critical insights into host-pathogen interactions and guide clinical and public health decisions. Because frequent testing is often infeasible, viral dynamics models are used to reconstruct infection trajectories, but optimal sampling strategies remain unclear. We compared two approaches for collecting SARS-CoV-2 viral load data: cross-sectional sampling (one measurement at symptom onset) and longitudinal sampling (every 3 days after onset) under constraints on the total number of tests and tests per individual. A viral dynamics model was first fitted to data from the National Basketball Association cohort, and the estimated parameters were treated as ground truth. Synthetic data were then generated under each sampling design, refitted, and evaluated for accuracy in estimating viral load over 30 days, peak viral load, peak time, and viral shedding duration. Longitudinal sampling consistently yielded lower root mean squared error and narrower one standard deviation interval than cross-sectional sampling. Peak timing and viral shedding duration were unbiased under both designs, but cross-sectional designs underestimated peak viral load and produced wider one standard deviation intervals. Coverage of viral load estimates was markedly higher for longitudinal designs (> 0.90) compared with cross-sectional ones (~0.10). Accuracy and coverage exceeded 0.96 even with just two tests per individual, with little additional benefit from more tests. In conclusion, longitudinal sampling-despite limited data-substantially improves accuracy and precision of viral load estimation compared with cross-sectional designs. These findings highlight efficient strategies for study design and resource allocation in infectious disease research.

PMID:41622893 | DOI:10.1002/jmv.70823

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HLA-Cw6 in Psoriatic Arthritis: Clinical Phenotype and Therapeutic Impact

J Clin Rheumatol. 2026 Feb 2. doi: 10.1097/RHU.0000000000002322. Online ahead of print.

ABSTRACT

BACKGROUND: Psoriatic arthritis (PsA) shares genetic features with psoriasis (PsO), with HLA-Cw6 being the main risk allele that may shape its clinical phenotype. This study aimed to evaluate the association between HLA-Cw6 status and clinical features, comorbidities, and treatment outcomes in PsA.

METHODS: We conducted a retrospective study of 426 patients with PsA who fulfilled the CASPAR criteria and had documented HLA-Cw6 status. Demographic, clinical, laboratory, and treatment-related variables were extracted from medical records. Patients were compared according to HLA-Cw6 positivity using descriptive, bivariate, and multivariate analyses.

RESULTS: HLA-Cw6 was present in 24.6% of the patients. HLA-Cw6-positive individuals were more frequently female (65.7% vs. 46.1%, P=0.001) and showed earlier PsO onset (28.0 vs. 35.3 y, P=0.009) and longer PsO-arthritis latency (17 vs. 9 y, P=0.024). Dactylitis was significantly less common in HLA-Cw6-positive patients (25.7% vs. 38.0%, P=0.022). HLA-Cw6-positive patients received more targeted therapies (1.8 vs. 1.5 drug classes, P=0.014) and had shorter TNFi persistence (17 vs. 36 mo, P=0.044). IL-12/23 inhibitors showed longer persistence in this group, although the difference was not statistically significant. In multivariate models, HLA-Cw6 was independently associated with female sex (OR: 4.11, P=0.003), lower frequency of dactylitis (OR: 0.33, P=0.020), and greater odds of difficult-to-manage PsA (OR: 12.53, P=0.001) and treatment-refractory PsA (OR: 15.39, P=0.001) based on recent EULAR definitions.

CONCLUSIONS: HLA-Cw6 identifies a PsA subset with distinctive clinical features and increased therapeutic complexity. These findings support the potential of HLA-Cw6 as a biomarker for PsA characterization and individualized therapy.

PMID:41622883 | DOI:10.1097/RHU.0000000000002322

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Community-based anti-stigma intervention for children with disabilities in Zambia

Disabil Rehabil. 2026 Feb 2:1-9. doi: 10.1080/09638288.2026.2621082. Online ahead of print.

ABSTRACT

BACKGROUND: Children with disabilities (CWD) experience greater obstacles than those without disabilities, including increased poverty, reduced healthcare opportunities, minimal educational resources, and stigma. This research explored the impact of community interventions on reducing stigma and discrimination toward children with disabilities.

METHODS: A repeated cross-sectional survey design (2019/2021) was implemented with community members in three low-resource compounds in Lusaka, Zambia, regarding stigma related to disability and participation in sensitization events via Kusumala+, a community-based intervention designed to improve quality of life for households with CWD. The analysis included descriptive statistics and linear regression assessing group mean change over time.

RESULTS: Participants included N = 259 (2019) and N = 1037 (2021). Subscales of stigma were identified: attitudes (t = 9.7, p < 0.001) and discrimination (t = 4.1, p < 0.001), which both significantly changed from baseline to follow-up. The effect size for the change in discrimination was d = 0.28 (95% CI 0.15-0.42) (weak to moderate effect) and for attitudes was d = 0.67(95% CI 0.53-0.81) (strong effect). Attitudes improved if event attendance occurred and increased with each additional event. In contrast, discrimination improved only when one event attendance occurred, not with each additional event change, in adjusted or unadjusted models.

CONCLUSION: Sensitization activities and events show promise as targeted interventions to reduce stigma and discrimination and create supportive community environments for CWD and their families.

PMID:41622874 | DOI:10.1080/09638288.2026.2621082

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Estimating Full Path Lengths and Kinetics from Partial Path Transition Interface Sampling Simulations

J Chem Theory Comput. 2026 Feb 2. doi: 10.1021/acs.jctc.5c01498. Online ahead of print.

ABSTRACT

Assessing the time scale of biological processes using molecular dynamics (MD) simulations with sufficient statistical accuracy is a challenging task, as processes are often rare and/or slow events, which may extend largely beyond the time scale of what is accessible with modern day high performance computational infrastructure. Recently, the replica exchange partial path transition interface sampling (REPPTIS) algorithm was developed to study rare and slow events involving metastable states along their reactive pathways. REPPTIS is a path sampling method where paths are cut short to reduce the computational cost, while combining this with the efficiency offered by replica exchange between the partial path ensembles. However, REPPTIS still lacks a formalism to extract time-dependent properties, such as mean first passage times, fluxes, and rates, from the short partial paths. In this work, we introduce a Markov state model (MSM) framework to estimate full path lengths and kinetic properties from the overlapping partial paths generated by REPPTIS. The framework results in newly derived closed formulas for the REPPTIS crossing probability, mean first passage times (MFPTs), flux, and rate constant. Our approach is then validated using simulations of Brownian and Langevin particles on a series of one-dimensional potential energy profiles as well as the dissociation of KCl in solution, demonstrating that REPPTIS accurately reproduces the exact kinetics benchmark. The MSM framework is further applied to the trypsin-benzamidine complex to compute the dissociation rate as a test case of a biological system, albeit the computed rate underestimates the experimental value. In conclusion, our MSM framework equips REPPTIS simulations with a robust theoretical and practical foundation for extracting kinetic information from computationally efficient partial paths.

PMID:41622863 | DOI:10.1021/acs.jctc.5c01498

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Psychological Flexibility as a Mediator Between Spiritual Coping and End-of-Life Care Attitudes in ICU Nurses: A Cross-Sectional Study

Nurs Crit Care. 2026 Mar;31(2):e70376. doi: 10.1111/nicc.70376.

ABSTRACT

BACKGROUND: Intensive care unit (ICU) nurses frequently encounter ethical dilemmas, patient death and emotional distress, which can shape attitudes towards end-of-life care. Spiritual coping and psychological flexibility may support nurses’ well-being and caregiving behaviour, but the mechanisms by which these factors affect ICU nurses’ attitudes towards end-of-life care remain underexplored, particularly in Eastern cultural contexts.

AIMS: To examine associations between spiritual coping, psychological flexibility and attitudes towards end-of-life care among ICU nurses, and to test whether psychological flexibility mediates the spiritual coping-attitude relationship.

STUDY DESIGN: A cross-sectional study was conducted between November and December 2024 in a large teaching hospital in China. Participants were selected using convenience sampling, and data were collected using the Chinese versions of the Spiritual Coping Questionnaire, Comprehensive Assessment of Acceptance and Commitment Therapy Processes (CompACT) and the End-of-Life Care Attitude Scale for Medical Workers. Descriptive statistics, group comparisons, Pearson correlations, multiple linear regression and PROCESS (Model 4) bootstrap mediation were used.

RESULTS: A total of 244 ICU nurses were included. Psychological flexibility and spiritual coping were positively correlated with attitudes towards end-of-life care (r = 0.635 and r = 0.282, both p < 0.001). In regression, psychological flexibility (p < 0.001), spiritual coping (p = 0.015), death education (p < 0.001), end-of-life care practice (p < 0.001) and educational level (p = 0.036) were significant predictors; the model explained 67.9% of the variance (R2 = 0.679). Bootstrap mediation showed a significant indirect effect of spiritual coping on attitudes via psychological flexibility (indirect effect = 0.118, 95% CI 0.064-0.193), accounting for 48.96% of the total effect.

CONCLUSIONS: ICU nurses with greater spiritual coping report more positive end-of-life care attitudes, partly through higher psychological flexibility. Interventions integrating Acceptance and Commitment Therapy-informed flexibility training with culturally sensitive spiritual support and structured death education may strengthen nurses’ preparedness for end-of-life care.

RELEVANCE TO CLINICAL PRACTICE: Incorporating psychological flexibility and spiritual coping into continuing education could enhance ICU nurses’ resilience and improve end-of-life care quality.

PMID:41622496 | DOI:10.1111/nicc.70376

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Cognitive impairment and altered structural connectivity after mild traumatic brain injury: A longitudinal study based on generalized q-sampling imaging

Neural Regen Res. 2026 Jan 27. doi: 10.4103/NRR.NRR-D-25-00498. Online ahead of print.

ABSTRACT

The pathophysiological mechanism of mild traumatic brain injury remains poorly understood. Generalized q-sampling imaging is applicable to a broad spectrum of diffusion imaging data, provides high-resolution depictions of the brain’s structural connectivity, enables tracking neural fibers across brain regions, and shows promise for predicting neurological outcomes. Graph theory, a quantitative method for modeling complex networks, has been widely used to study changes in brain structure and function. This longitudinal observational study involved 34 patients with acute mild traumatic brain injury (12 men and 22 women) and 31 healthy controls (14 men and 17 women). Clinical and cognitive assessments, and magnetic resonance imaging scans were conducted within 72 hours and at 3 months post-injury. Subsequent graph theory and statistical analyses showed that generalized q-sampling imaging-based structural brain networks captured small-worldness in patients with mild traumatic brain injury compared with healthy controls. Patients with mild traumatic brain injury exhibited cognitive deficits, which showed improvement at the 3-month follow-up. The results also indicated changes in betweenness centrality, node efficiency, and node clustering coefficient of the left fusiform gyrus in patients with chronic mild traumatic brain injury, and an increase in connectivity strength between the bilateral anterior cingulate cortices. Preliminary explanations were made based on neural plasticity and compensatory mechanisms. The underlying mechanisms remain to be further explored in our subsequent research.

PMID:41622453 | DOI:10.4103/NRR.NRR-D-25-00498