Biomedicines最新文献

Background: Head and neck squamous cell carcinoma remains a highly aggressive malignancy with limited predictive biomarkers for prognosis and radiotherapy response. Increasing evidence indicates that pseudogenes are functionally active regulators of cancer biology, yet their clinical relevance in HNSCC is poorly defined. Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas, we analyzed the expression and clinical significance of two pseudogenes, ANXA2P2 and PA2G4P4, in HNSCC. Associations with clinicopathological features, HPV status, tumor subtypes, survival, genomic instability, radiotherapy response, and immune landscape were assessed using bioinformatic tools. Results: Both pseudogenes were significantly upregulated in HNSCC compared to normal tissues. Higher expression levels correlated with adverse clinicopathological features, increased tumor proliferation and wound-healing capacity, and unfavorable TCGA molecular subtypes. High ANXA2P2 and PA2G4P4 expression was associated with reduced overall survival, while their combined low-expression signature identified patients with significantly improved overall and disease-free survival. Notably, lower expression of both pseudogenes was observed in patients responding to radiotherapy, whereas higher expression was linked to genomic instability parameters and enrichment of oncogenic pathways, including MYC, PI3K/AKT/mTOR, cell cycle regulation, and DNA repair. ANXA2P2 expression differed significantly by HPV status, showing reduced levels in HPV-positive tumors. Furthermore, pseudogene expression stratified distinct immune profiles, including immune subtypes, stromal and immune scores, and specific immune cell populations. Conclusions:ANXA2P2 and PA2G4P4 are clinically relevant pseudogenes associated with tumor aggressiveness, immune modulation, and radiotherapy response in HNSCC. These findings support their potential utility as prognostic and predictive biomarkers and provide a rationale for further functional validation in experimental models.

Background: Allergic rhinitis (AR) is a chronic immunoglobulin E (IgE)-mediated inflammatory disorder triggered by aeroallergens. Oxidative stress (OS) is increasingly recognized as a key factor in AR pathophysiology. This study aimed to investigate dynamic thiol-disulfide homeostasis (TDH) and OS markers in AR patients compared to healthy controls. Methods: Sixty-two participants (31 AR patients, 31 controls) were enrolled. Hematological and biochemical parameters were measured. OS markers including total thiol (TT), native thiol (NT), disulfide, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed. Correlations between OS markers and laboratory parameters were analyzed. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of OS markers. Results: TT and NT levels were significantly lower in AR patients, whereas disulfide, disulfide/NT and disulfide/TT ratios, TOS and OSI were significantly higher. TAS levels were slightly lower in AR patients. TT and NT correlated positively with eosinophil counts and negatively with monocyte, platelet, AST, and creatinine levels. ROC analysis indicated strong diagnostic potential: TT (AUC = 0.749, cutoff 415 µmol/L, sensitivity 90%, specificity 61%), NT (AUC = 0.786, cutoff 373.2 µmol/L, sensitivity 90%, specificity 71%), and disulfide (AUC = 0.690, cutoff 20 µmol/L, sensitivity 74%, specificity 61%). Conclusions: AR patients exhibit disrupted TDH and elevated OS. These markers may serve as sensitive indicators of oxidative imbalance, offering potential diagnostic and therapeutic insights into AR management.

Background: Acacetin, a naturally occurring flavone present in various plants, is known as a promising drug candidate for cardiovascular disorders. Our previous study demonstrated that acacetin ameliorates atherosclerosis through endothelial cell protection; however, its pharmacological effects on vascular smooth muscle cells (VSMCs) remain unexplored. This study investigates the therapeutic potential of acacetin against lysophosphatidylcholine (LysoPC)-induced VSMC injury and elucidates the underlying molecular mechanisms. Methods and Results: Multiple biochemical techniques were employed in the present study. The results showed that acacetin significantly attenuated LysoPC-induced apoptosis and reactive oxygen species (ROS) generation in cultured VSMCs. Western blot analysis revealed that the cytoprotection of acacetin was associated with upregulated expression of antioxidant defense proteins, including nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), NADPH quinone oxidoreductase 1 (NQO-1), and superoxide dismutase 1 (SOD1). Nrf2 silencing completely abolished these protective effects. Mechanistically, siRNA-silencing of Sirtuin 1 (Sirt1) abrogated acacetin-induced modulation of the Nrf2/Keap1/p62 signaling. In vivo validation using aortic tissues from high-fat-diet-fed ApoE^-/- mice confirmed that acacetin effectively suppressed VSMC apoptosis and ROS overproduction associated with restoring the downregulated Sirt1 expression levels. Conclusions: These findings establish a novel mechanistic paradigm wherein acacetin confers protection against LysoPC-induced VSMC apoptosis and oxidative stress through Sirt1-dependent activation of the Nrf2/p62 signaling pathway, suggesting that acacetin is a promising therapeutic drug candidate for atherosclerotic plaque stabilization.

Background: Recently, based on HOMA-IR, we estimated empirical optimal cut-off values for SHBG levels of ≤41.5 nmol/L in women with PCOS. Other proposed markers of insulin resistance include triglyceride and glucose levels, and anthropometric measurements. Therefore, our current study aimed to analyze its consistency with the cut-off values that discriminate insulin resistance based on the TyG, TyG-BMI, and TyG-WC indices in women with PCOS. Methods: Age, body weight, height, waist circumference, glucose, insulin, triglyceride, and SHBG levels were retrieved from the medical records of 264 Caucasian women diagnosed with PCOS. The TyG, TyG-BMI, and TyG-WC indices were calculated. The mean meta-cut-off SHBG level was calculated using receiver-operating characteristic (ROC) analysis combined with diagnostic test accuracy meta-analysis. Results: The mean meta-cut-off value for SHBG levels for the assessment of insulin resistance was less than 43.1 (95% CI: 37.0-49.2) nmol/L. The pooled sensitivity and specificity of SHBG levels for the assessment of insulin resistance were 74.7% and 66.9%, respectively. The pooled mean prevalence of insulin resistance based on all indices was 36.1% (95% CI: 33.5-38.7%) with a standard deviation of 18.7% and positive predictive value (PPV) of 52.8% (95% CI: 12.2-87.5%) and the negative predictive value (NPV) of 80.2% (95% CI: 45.1-97.7%). Conclusions: Our study confirms the usefulness of SHBG level as a marker of insulin resistance in Caucasian women with PCOS. A value below 43 nmol/L, with high sensitivity and specificity, enables the detection of insulin resistance and a high risk of prediabetes, prompting close monitoring of liver function.

Background: Fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD) may co-occur and are associated with increased symptom burden, functional impairment, and reduced quality of life. Accumulating evidence suggests shared neurobiological mechanisms. Trauma-focused interventions targeting maladaptive memory processes may therefore represent a relevant therapeutic approach in this population. Objective: To evaluate the feasibility, tolerability, and preliminary clinical associations of a brief reconsolidation-based therapy in women with comorbid FMS and PTSD. Methods: This multicenter pilot study included adult women diagnosed with FMS and PTSD who underwent six sessions of reconsolidation therapy combining traumatic memory reactivation with propranolol administration. Clinical outcomes were assessed at baseline and at 3-month follow-up using the Fibromyalgia Impact Questionnaire (FIQ), the Impact of Event Scale-Revised (IES-R), the Montgomery-Åsberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI), the Rosenberg Self-Esteem Scale (RSES), and the SF-36. Changes over time were analyzed using paired statistical tests and linear mixed-effects models. Results: Fourteen participants completed the intervention and follow-up assessments. The intervention was feasible and well tolerated. Changes over time were observed in fibromyalgia-related quality of life (FIQ scores), PTSD symptom severity (IES-R), and depressive symptoms (MADRS, BDI), as well as in selected SF-36 domains, including vitality, social functioning, and mental health. A progressive decrease in IES-R scores was observed across treatment sessions. Conclusions: This pilot study suggests that reconsolidation-based therapy is feasible in women with comorbid FMS and PTSD and was associated with changes in PTSD symptoms and fibromyalgia-related functional impact. Given the exploratory design and absence of a control group, these findings should be interpreted cautiously and warrant confirmation in larger, controlled trials.

Pancreatic adenocarcinoma is one of the most aggressive malignancies, with a steadily increasing incidence rate. Due to the asymptomatic nature of early cancer and frequent late diagnosis, only 10-20% of patients are considered for radical treatment. In approximately 40% of patients, local advancement precludes primary surgical treatment, and in approximately half of patients, the cancer is diagnosed at the metastatic stage. Treatment of advanced pancreatic cancer is based on systemic therapy, while a growing number of studies are focusing on the potential use of molecularly targeted agents. The median survival time for metastatic patients treated with FOLFIRINOX chemotherapy is 11 months, compared to 8.5 months for patients treated with gemcitabine and nab-paclitaxel-based chemotherapy. Olaparib in the maintenance treatment of patients with advanced pancreatic cancer prolongs the time to progression compared to placebo but does not affect median overall survival. Immunotherapy and targeted therapy have so far been used in a narrow group of patients with a specific molecular profile, but further research on this cancer offers a real opportunity to develop new treatment approaches. This review article is based on the NCCN (National Comprehensive Cancer Network) guidelines and publications available in the PubMed database.

Lung cancer remains the leading cause of cancer-related deaths globally, with around 2 [...].

Background/Objectives: Retinitis pigmentosa is a degenerative retinal disease and a major cause of inherited blindness globally. The pro-survival kinase AKT is downregulated in degenerating photoreceptors in retinitis pigmentosa, and its activation has shown neuroprotective effects in retinitis pigmentosa and other neurodegenerative disorders. In this study, we evaluated the therapeutic potential of SC79, a pharmaceutical AKT activator, in two mouse models of retinitis pigmentosa, rd1.GFP and RhoP23H.GFP. Methods: SC79 was administered intravitreally at postnatal day 12 (P12) and analysis was conducted at P16. Results: SC79 at 10 µM was well tolerated in wildtype mice, with no reduction in retinal function or thickness. In rd1.GFP mice, SC79 partially preserved peripheral outer nuclear layer (ONL) thickness, improved rod photoreceptor-driven optomotor contrast sensitivity responses, and improved cone photoreceptor morphology. Immunohistochemistry of retinal sections indicated AKT-related protein expression changes in both sham and SC79-treated rd1.GFP retinas, with sham injections leading to decreases in this pathway and SC79 injections restoring this back to uninjected protein levels or higher, indicating the damage from intravitreal injections can induce AKT-related protein expression changes. In RhoP23H.GFP mice, changes to the visual response from the therapeutic effects of SC79 were not detectable. An increased dosage of SC79 at 100 µM was evaluated in wildtype mice and showed no major toxic effects, although it did not confer neuroprotective benefits in either disease model. Conclusions: These results demonstrate the potential therapeutic effect of AKT pathway modulation for preserving photoreceptors in recessive retinitis pigmentosa, with further optimisation of treatment delivery required.

Background/Objectives: Long COVID (LC) is associated with more than 200 symptoms. This study aimed to evaluate the correlation between symptoms clusters and pharmacological treatment in patients with LC and to explore differences by sex. Methods: We conducted a cross-sectional descriptive study including 304 participants diagnosed with LC according to the World Health Organization criteria. Symptoms during the acute phase, at the time of diagnosis of LC, and those persisting across both phases were collected by anamnesis. Symptoms were grouped into six clusters: systemic, neurocognitive, respiratory/cardiovascular, musculoskeletal, neurological/neuromuscular, and psychological/psychiatric. Drug use was assessed through a questionnaire verified by the medical records, including the consumption of cardiovascular drugs, antidepressants/anxiolytics, and anti-inflammatory/analgesics. Results: Patients reported a mean of 5.23 ± 1.10 symptoms in the acute phase, 4.20 ± 1.70 at LC diagnosis, and 3.83 ± 1.80 persisting across both phases. The most consumed pharmacological group was cardiovascular drugs (43.3%), followed by antidepressants/anxiolytics (34.8%). Psychotropic drugs and anti-inflammatory/analgesic drugs showed a positive association with all symptomatic groups (p < 0.05). Cardiovascular drugs showed a positive association with cardiorespiratory (β = 0.19, p < 0.05), neuromuscular (β = 0.11, p < 0.05), and psychological (β = 0.14, p < 0.05) symptoms. Conclusions: Psychotropic and anti-inflammatory/analgesic drugs were positively associated with all symptom clusters, while cardiovascular drugs were associated only with cardiorespiratory, neuromuscular, and psychological symptoms, highlighting the relevance of better characterization of treatment patterns in this population.

Background: Aloe vera gel in 0.3% hyaluronate (AV/HA) could mitigate glaucoma therapy-related ocular surface disease (GTOSD). Methods: Thirty-nine patients diagnosed with GTOSD and receiving AV/HA or HA underwent ocular surface disease index (OSDI), Symptom Assessment iN Dry Eye (SANDE), National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 questionnaires, and tear matrix metalloproteinase-9 (MMP-9), break-up time (BUT), corneal fluorescein staining (CFS), Schirmer test I (STI), and bulbar conjunctival hyperemia (BCH) determination. Results: After one month, AV/HA increased BUT (5 (7-4.5) to 7 (8-5.5)) and STI (12 (19.5-8) to 13.5 (20-10)), while it decreased BCH (2.2 (2.3-1.3) to 2.1 (2.2-1.2)) and CFS (3 (4-2) to 2 (3.0-1.5)) (p < 0.001). SANDE and OSDI scores were reduced from 36.18 (38.5-20.5) to 22.91 (31.5-17.21), and 29.5 (32.5-19.5) to 20 (26.5-18) (p < 0.001). HA reduced BCH from 2.75 (3.20-2.15) to 2.25 (2.30-1.90) (p = 0.014) and CFS from 3.5 (5-2.75) to 2.5 (4-2) (p = 0.014), while it increased BUT (p = 0.036). The SANDE score decreased from 28.95 (47.6-20.9) to 26.86 (36.41-19.90) (p = 0.009), whereas the OSDI decreased from 40 (49-19.5) to 29 (42-19.75) (p = 0.005). Any significant change in NEI VFQ-25 was collected. A trend for an MMP-9 immunoassay positivity reduction was observed in AV/HA (0.073). Conclusions: These findings invite considering lubricants enriched with natural anti-inflammatory agents, such as Aloe vera, as a potential adjunctive option to improve the ocular surface in glaucoma.