Background Patellar tendinopathy (PT) is a common overuse knee injury causing anterior pain. Therapeutic ultrasound, eccentric exercise, and topical curcumin are suggested to support tendon repair via anti-inflammatory effects. This randomized control trial (RCT) was planned to assess better combination for the management of PT. Methods This prospective, parallel-group, assessor-blinded RCT (IRCT20230202057310N16) was conducted at a physiotherapy center in Multan, Pakistan (Jan 2025–May 2025). Parallel-group assessor-blinded randomized controlled trial was done Muhammad Rehabilitation Clinic from December 2024 to May 2025. Ninety out of 110 participants meeting inclusion criteria were recruited. Participants were randomly allocated to Group A (n=45) or Group B (n=45). Fourteen patients were lost to follow-up. Thus, thirty-eight patients were analyzed per group. Intervention Group A: 2g topical curcumin-alloe vera gel plus supervised eccentric exercise, three-four times weekly for 6-8 weeks. Group B: 2g topical curcumin-alloe vera gel administered using phonophoresis (1MHz, 1.5W/cm 2 , pulsed, 10 minutes). Outcomes prospectively registered were: VISA-P. pain (numeric pain rating scale-NPRS), KOOS, strength, range of motion, SF-36, ESR, CRP and patella tendon thickness Molecular docking of curcumin against NF-κB, COX-2, IL-6, MMPs, TGF-β1, 5-lipoxygenase, and TNF-α was also performed. Results Both groups improved significantly across all domains (p≤0.005). Group B showed better NPRS (3.02±2.05 vs 5.98±2.12, p<0.001) and lower CRP/ESR (p<0.005). Group A had superior VISA-P (79.2±7.2 vs 72.8±7.5), KOOS, strength, and ROM (all p<0.001). Conclusion Both strategies benefited PT patients. Phonophoresis excelled in global pain and systemic inflammation; exercise combination was superior for activity-related pain and function. Complementary profiles support personalized care. Long-term follow-up studies are needed. Registration Iranian Clinical Trial Registry : https://www.irct.ir/trial/80759 .
Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Surfactant protein D (SP-D), encoded by the SFTPD gene, has been strongly implicated in COPD through genetic associations, protein-level biomarkers, and functional studies. However, whether SFTPD is dysregulated at the transcriptomic level in lung tissue remains unclear. Objectives To evaluate whether SFTPD is transcriptionally dysregulated in COPD lung tissue. Design Retrospective transcriptomic analysis of publicly available RNA-seq data. Methods We re-analyzed publicly available RNA-seq data from lung tissue samples (BioProject: PRJNA1151128) comprising COPD patients (n = 9) and control subjects (n = 9) using a reproducible bioinformatics workflow (HISAT2, StringTie, edgeR with FDR correction). In addition to differential expression testing, we calculated effect sizes and performed post-hoc power analysis to rigorously assess the robustness of null findings. Furthermore, findings were validated using an independent microarray dataset (GSE47460). Results Overall, 114 genes were upregulated and 104 were downregulated in COPD lung tissue compared with controls. In contrast, SFTPD expression was not significantly differentially expressed (log 2 FC = 0.316; FDR = 0.421). The effect size was small (Cohen’s d = 0.42), and power analysis indicated 23% sensitivity to detect the observed fold change, though 80% power was achieved for ≥2.1-fold changes. Conclusion This study evaluated whether SFTPD is transcriptionally dysregulated in COPD lung tissue using RNA-seq data and demonstrates that SFTPD mRNA levels are not significantly altered. These findings suggest that COPD-associated alterations in SP-D arise through post-transcriptional or systemic mechanisms rather than lung tissue transcription. These findings were further supported by external validation using a large public lung tissue dataset. By rigorously validating and reporting a null result, this work reduces publication bias, informs biomarker strategies, and highlights the need for integrative single-cell and multi-omics approaches to clarify SP-D regulation in COPD.
Cancer is a complex disease influenced by genetic mutations, metabolic reprogramming, and diverse tumor microenvironments, all of which affect disease progression and treatment outcomes. Personalized vaccinology has emerged as a promising approach, using individual tumor genomics, and molecular profiles to design tailored cancer vaccines. Complementing genomics analyses, metabolomics provides a comprehensive assessment of small-molecule metabolites that reflect the functional state of tumors and the host immune system. By identifying tumor and patient-specific metabolic signatures, metabolomics can reveal biomarkers associated with vaccine responsiveness, uncover immunosuppressive pathways within the tumor microenvironment, and support strategies to enhance effective vaccine design. By integrating metabolomics with genomics and proteomics, precision cancer vaccines can maximize antitumor effects, reduce off-target responses, and account for inter-patient variability. This review focuses on the role of metabolomics in guiding the design and clinical optimization of personalized cancer vaccines, highlighting its potential to improve next-generation cancer therapies.
Background: Neurodegeneration in the cornea, particularly in diabetic patients, is an emerging area of research that highlights the potential of tear fluid as a source of biomarkers. Neurofilaments light chain (Nf-L), which are structural proteins found in neurons, have been identified as promising candidates for early biomarkers of neurodegeneration. Objective: This study investigates the correlation Nf-L levels in tears and corneal in vivo confocal microscopy (IVCM) parameters in patients with diabetes mellitus without retinopathy with the aim of associating Nf-L level with corneal neurodegeneration. Design: Case-control observational study. Methods: We enrolled 20 patients with diabetes mellitus type 2 (DM) and 20 healthy controls (HC): we studied the levels of Nf-L in serum and tears, and we looked for a correlation with the parameters detected on IVCM, including corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD) and corneal nerve branching density (CNBD). Results: Serum Nf-L levels showed no difference between DM (mean ± SD 14.00 ± 2.18 pg/mL) and HC (mean ± SD 15.18 ± 2.28 pg/mL). Instead we detected a significant increase in Nf-L levels in DM tears (right eye mean ± SD 321.23 ± 192.40 pg/mL; left eye mean ± SD 277.90 ± 254.23 pg/mL) compared to HC (right eye mean ± SD 25.80 ± 22.0 pg/mL; left eye mean ± SD 27.96 ± 20.21 pg/mL). Furthermore, a negative correlation was evident between Nf-L levels and IVCM parameters: CNFL/Nf-L r −.4234 P < .001; CNFD/Nf-L −.4959 P < .001; CNBD/Nf-L r −.5310 P < .0005. Conclusion: Our findings indicate that Nf-L levels are significantly elevated in the tears of DM patients and that high Nf-L levels correlate with lower corneal IVCM parameters, suggesting that tears Nf-L could be a reliable biomarker for early corneal neurodegeneration in diabetes without retinopathy.
Background Khat (Catha edulis) is a widely consumed stimulant in East Africa, but its role in hepatocellular alterations remains debated. Objectives This study evaluated the association between khat consumption patterns and subclinical liver injury in Somaliland. Design A hospital-based case-control study. Methods The study was conducted at Hargeisa Group Hospital (N = 260). Biochemical markers were compared among current, past, and non-chewing controls. Because khat use was absent among females, multivariable logistic regression was restricted to males (n = 188). Serum AST, ALT, and bilirubin were analyzed using the Kruskal–Wallis H test and bootstrap BCa 95% confidence intervals. Results Current khat chewers exhibited significantly higher median AST (76.50 vs. 39.50 U/L), ALT (75.00 vs. 42.50 U/L), and total bilirubin (1.45 vs. 0.30 mg/dL) levels than non-chewers (all p < 0.001). Biochemical markers in past chewers did not differ significantly from controls (p > 0.05). Total bilirubin >3 mg/dL was observed across all groups but was more prevalent among current chewers (37.3%) than non-chewers (30.9%) and past chewers (6.3%) (p = 0.003). ALT >3× ULN was more frequent among current chewers (p = 0.020), whereas AST >3× ULN did not differ significantly (p = 0.256). Current khat chewing independently predicted hepatocellular injury (AOR = 3.73; 95% CI: 1.40–9.95; p = 0.009). A dose-response pattern was observed, with consumption ≥250 g/session (AOR = 2.45; p = 0.038) and duration >10 years (AOR = 5.08; p = 0.001) associated with increased odds of injury. Conclusion Active khat consumption among males was associated with dose-dependent subclinical hepatocellular injury. The absence of abnormalities in past chewers may suggest stabilization after cessation. Given the observational design, these findings should be interpreted as associations rather than evidence of causality and warrant prospective studies with comprehensive hepatobiliary assessment.
