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Adv Clin Exp Med [JOURNAL]

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The role of urinary biomarkers in the diagnosis, prognosis and pathophysiology of heart failure with preserved ejection fraction.

Nasiadka AA, Rydzewska-Rosołowska A, Kakareko K … +2 more , Głowińska I, Hryszko T

Adv Clin Exp Med · 2025 Nov · PMID 40748768 · Publisher ↗

Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge due to its increasing incidence, diagnostic complexities and pathophysiological heterogeneity. This study offers valuable insi... Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge due to its increasing incidence, diagnostic complexities and pathophysiological heterogeneity. This study offers valuable insights into the role of urinary biomarkers in patients with HFpEF. Our research focused on profiling alterations in urinary biomarkers, encompassing albumin, indicators of tubular injury, oxidative stress markers, and proteomic changes in individuals with this condition. These findings may provide a potential tool for addressing the diagnostic challenges associated with HFpEF, particularly given the absence of specific cutoff points in the diagnosis of this disease. Furthermore, we explored the potential pathophysiological relationships of these biomarkers, which, in a broader context, facilitate a deeper understanding of this complex disease and may identify potential pharmacotherapeutic targets. We also examined the prognostic value of the identified biomarkers, which could serve as useful instruments for predicting disease risk and forecasting clinical outcomes. Additionally, we emphasized the existing knowledge surrounding potential biomarkers, suggesting that a better understanding of these markers may contribute to the development of clinically relevant tools and enhance our comprehension of HFpEF. The findings from this study align with the current literature, which underscores the complexity of HFpEF and the need for innovative diagnostic, prognostic and therapeutic strategies.

ERAS protocols for oral cancer free tissue transfer reconstruction: Critical review and clinical checklist.

Jaxa-Kwiatkowski AM, Leszczyszyn A, Gerber H

Adv Clin Exp Med · 2025 Sep · PMID 40742194 · Publisher ↗

The Enhanced Recovery After Surgery (ERAS) consensus offers a robust framework but must be tailored to the unique challenges of free-tissue transfer reconstructions in oral cancer. Factors such as clinical heterogeneity,... The Enhanced Recovery After Surgery (ERAS) consensus offers a robust framework but must be tailored to the unique challenges of free-tissue transfer reconstructions in oral cancer. Factors such as clinical heterogeneity, institutional variability, inconsistent monitoring, and the absence of internal compliance audits can undermine postoperative recovery. By fostering multidisciplinary collaboration, ERAS can evolve from a theoretical guideline into a reproducible clinical pathway that enhances survival, functional outcomes and quality of life for oral cancer patients undergoing free-tissue reconstruction. Our proposed checklist merges evidence-based recommendations with practical adaptations to establish a more consistent, auditable and outcome-driven approach to perioperative care.

Traumatic complications linked to prophylactic drain placement after hepatectomy: A meta-analysis.

Fei Z, Duan X, Liang J … +2 more , Sun Z, Tang J

Adv Clin Exp Med · 2025 Dec · PMID 40742193 · Publisher ↗

BACKGROUND: Research documenting the results of liver trauma surgery revealed a connection between prophylactic drainage (PD) and escalating infections or septic consequences. OBJECTIVES: Meta-analysis research was condu... BACKGROUND: Research documenting the results of liver trauma surgery revealed a connection between prophylactic drainage (PD) and escalating infections or septic consequences. OBJECTIVES: Meta-analysis research was conducted to review the wound complications (WCs) frequency of PD in liver resections (LRs). MATERIAL AND METHODS: Up until June 2024, comprehensive literature study was completed, and 757 related studies were reviewed. The 10 selected studies included 5,459 LRs at the beginning; 2,918 of them were drained and 2,541 were not. The dichotomous approaches and a fixed or random model were used to assess the WCs frequency of PD in LRs using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Prophylactic drainage had significantly higher surgical site wound infection rate (OR = 1.97; 95% CI: 1.09-3.55, p = 0.02) compared to non-PD in in LR patients, though no significant difference was found among PD and non-PD in LR patients in infected intra-abdominal collections (IIACs; OR = 3.17; 95% CI: 0.93-10.80, p = 0.07). CONCLUSION: Prophylactic drainage had a considerably greater surgical site wound infection rate, and there was no discernible difference between IIACs and non-PD in LR individuals. Nevertheless, because there were not many studies nominated for comparison in the meta-analysis, care must be used when working with its outcomes, and further research is warranted to confirm these findings.

Next-generation sequencing study of inflammatory spindle cell lesions focused on receptor tyrosine kinase gene rearrangements most frequently occurring in inflammatory myofibroblastic tumor.

Siemion K, Kiśluk J, Wasilewska N … +4 more , Reszec-Gielażyn J, Korzyńska A, Łysoń T, Mariak Z

Adv Clin Exp Med · 2025 Dec · PMID 40742192 · Publisher ↗

BACKGROUND: A group of inflammatory spindle cell lesions (ISCLs) includes many nosological entities with a common histological image consisting of spindle-shaped cells and inflammatory infiltrate. Diverse diseases indica... BACKGROUND: A group of inflammatory spindle cell lesions (ISCLs) includes many nosological entities with a common histological image consisting of spindle-shaped cells and inflammatory infiltrate. Diverse diseases indicate different prognoses that can be difficult to predict. The most well-known neoplasm from the group is an inflammatory myofibroblastic tumor (IMT) that harbors tyrosine kinase gene rearrangement frequently affecting ALK, ROS1, RET, PDGFRB, NTRK, and IGF1R genes. In contrast, a reactive mass-forming lesion is regarded as an inflammatory pseudotumor (IPT). OBJECTIVES: This study aimed to: 1) investigate the accuracy of the primary diagnosis of IMT and IPT with the diagnostics using extended analysis of clinical data, re-evaluation of histopathological slides and next-generation sequencing (NGS); and 2) to establish prognostic and diagnostic factors. MATERIAL AND METHODS: Finally, 46 cases of ISCLs were retrieved. The authors revised diagnoses and performed NGS based on ribonucleic acids isolated from selected paraffin blocks. Clinical and paraclinical data were also collected. The final diagnoses were made as a result of available information integration. RESULTS: The sequencing confirmed 4 IMTs and detected 4 fusion gene types - EML4-ALK, RANBP2-ALK, and ETV6-NTRK3. Additionally, 1 afunctional EGFR-PPARGC1A rearrangement was found in gastric inflammatory fibroid polyp. A subset of reactive lesions also contained some mutations, which is consistent with actual knowledge. Neoplasms with ganglion-like cells, nuclear atypia and increased mitotic activity gave local recurrences. A higher percentage of necrosis indicated IMTs and patients who died in the analyzed period. No relation between genetic alterations and relapse was found. CONCLUSIONS: A final diagnosis can be made based on all clinical and paraclinical data. The prognosis after the treatment is dependent on the pathological diagnosis, disease location and resection completeness, presence of ganglion-like cells, nuclear atypia, mitotic index, and necrosis. Not only neoplastic but also reactive lesions can recur. The presence of gene rearrangements and necrosis can have diagnostic value.

MALAT1 modulates granulosa cells ferroptosis and apoptosis through PAK2 upregulation in polycystic ovary syndrome.

Yang Y, Li D, Sun L … +1 more , Liu S

Adv Clin Exp Med · 2025 Dec · PMID 40742191 · Publisher ↗

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated endocrinological disorder. OBJECTIVES: We investigated the ferroptosis-regulated role of MALAT1 and its potential modulatory mechanisms in granulosa cells (GC... BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated endocrinological disorder. OBJECTIVES: We investigated the ferroptosis-regulated role of MALAT1 and its potential modulatory mechanisms in granulosa cells (GCs). MATERIAL AND METHODS: Reverse transcripton quantitative polymerase chain reaction (RT-qPCR) was used to measure the relative expression of MALAT1/miR-155-5p/PAK2 in KGN cells after transfection. Online bioinformatic analysis was performed to predict the interactions between MALAT1/PAK2 and miR-155-5p. Dual luciferase assays were performed for relative luciferase activity in cell groups co-transfected with the pmiRGLO plasmids containing wild type (wt) or mutant type (mt) of MALAT1 (MALAT1-wt, MALAT1-mt), siRNA targeting MALAT1(si-MALAT1) miR-155-5p inhibitor or their control was transfected into KGN cells using Lipofectamine 2000. After 48 h, the transfected cells were collected for the following experiments. Cell viability and apoptosis were measured using Cell Counting Kit-8 (CCK-8) and flow cytometry. Malondialdehyde (MDA) level and reduced glutathione (GSH) / oxidized glutathione disulfide (GSSG) ratio were detected using commercial kits. Western blot was used to measure the relative protein changes in PAK2, SLC7A11 and GPX4. RESULTS: Knockdown of MALAT1 decreased cell viability, increased apoptosis and ferroptosis, which was reversed by miR-155-5p inhibition. MALAT1 downregulation inhibited PAK2, while miR-155-5p inhibition activated PAK2. The increase of relative luciferase activity in cells transfected with MALAT1-wt or PAK2-wt and miR-155-5p inhibitor suggests the bindings between miR-155-5p and MALAT1 or PAK2. CONCLUSIONS: This study revealed a novel ferroptosis-modulated role of MALAT1 in PCOS in vitro via interactions with miR-155-5p/PAK2. Further in vivo and clinical studies are needed to validate these in vitro findings and fully assess the therapeutic potential of MALAT1 in PCOS.

Peritoneal dialysis catheter removal at the time or after kidney transplantation: A multicenter cardinality-matched cohort study.

Zawistowski M, Niecikowski P, Durlik M … +15 more , Nowaczyk J, Broda J, Foroncewicz B, Mucha K, Widera M, Król R, Stadnik H, Karczewski M, Kruszyna T, Niekowal B, Korus J, Kamińska D, Krajewska M, Kosieradzki M, Domagała P

Adv Clin Exp Med · 2025 Nov · PMID 40742190 · Publisher ↗

BACKGROUND: Evidence regarding the optimal timing of peritoneal dialysis catheter (PDC) removal in renal graft recipients is limited. While some centers opt for removal during the transplant procedure, others defer cathe... BACKGROUND: Evidence regarding the optimal timing of peritoneal dialysis catheter (PDC) removal in renal graft recipients is limited. While some centers opt for removal during the transplant procedure, others defer catheter removal to various time points post-transplantation. OBJECTIVES: In this multicenter cardinality-matched cohort study, we aimed to determine the optimal timing of PDC removal in patients undergoing kidney transplantation. MATERIAL AND METHODS: Data from 324 patients were collected across 5 centers. We compared patients who had catheters removed during renal transplant (the PDC-free group) with those who had them removed after the procedure (the PDC group), matched 1:2 by age, sex, body mass index (BMI), living, and extended criteria donor statuses. We evaluated: 1) the need for dialysis within 2 post-transplant months, 2) a composite endpoint of catheter-related infection, peritonitis and/or surgical site infection, and 3) the length of hospitalization. RESULTS: After cardinality matching, the groups were well-balanced across all matching covariates. Postoperative dialysis was required in 14% of patients, with no statistically significant difference observed between the PDC-free and PDC groups (19% vs 12%; odds ratio (OR) = 1.94; 95% confidence interval (95% CI): 0.78-4.81; p = 0.152). Of the 14 patients in the PDC group who required dialysis postoperatively, only 3 were managed with peritoneal dialysis. No statistically significant difference was noted for the composite endpoint (8.6% vs 6.2%; OR = 0.74; 95% CI: 0.20-2.77; p = 0.656). Hospitalization was significantly longer in patients from the PDC group (median [interquartile range (IQR)]: 11 [9-15] vs 9 [7-12]; BM = -3.036; p = 0.003). CONCLUSIONS: This study did not demonstrate any benefits associated with delaying PDC removal in renal graft recipients. On the contrary, postponing removal was linked to prolonged hospitalization.

Reconstruction of outer glycolipid synthesis pathways from Porphyromonas gingivalis in Escherichia coli for production of a vaccine candidate.

Brzozowska E, Świętnicki W, Sycz J … +6 more , Kołodziejczak M, Stachowicz Ł, Wzorek A, Korzeniowska-Kowal A, Skowicki M, Lipiński T

Adv Clin Exp Med · 2025 Dec · PMID 40708554 · Publisher ↗

BACKGROUND: Porphyromonas gingivalis is a major human oral opportunistic pathogen and a key etiological agent of periodontal disease, contributing to inflammation and bone loss in the oral cavity. Periodontitis is not li... BACKGROUND: Porphyromonas gingivalis is a major human oral opportunistic pathogen and a key etiological agent of periodontal disease, contributing to inflammation and bone loss in the oral cavity. Periodontitis is not limited to oral health complications; it has also been associated with a range of systemic conditions, including coronary heart disease (CAD), respiratory disease, rheumatoid arthritis, chronic kidney disease (CKD), and certain types of cancer. OBJECTIVES: Immunization-based prevention of periodontitis appears to be a promising strategy; however, no vaccine is currently available for commercial use. In the present study, a novel vaccine candidate against P. gingivalis was proposed, consisting of a P. gingivalis protein, gingipain, glycosylated with the carbohydrate moiety of P. gingivalis lipopolysaccharide (LPS). MATERIAL AND METHODS: Glycosylation of gingipain was achieved in Escherichia coli by introducing the Campylobacter jejuni N-glycosylation system, the P. gingivalis LPS biosynthetic pathway and the gingipain gene. RESULTS: The neoglycoprotein was purified using column chromatography to a purity exceeding 99%, yielding a soluble antigen. The modified protein was recognized by commercial antibodies targeting the protein backbone, the carbohydrate moiety, and a custom monoclonal antibody specific to the purified LPS of P. gingivalis American Type Culture Collection (ATCC) 33277. The glycoprotein was used to immunize mice, and the resulting sera were analyzed for their ability to opsonize bacterial cells. The absence of detectable opsonization suggests that the elicited antibodies are more likely directed against the protein component of the vaccine rather than the glycan surface antigen. CONCLUSIONS: The final product was most likely assembled correctly, as it was recognized by LPS-specific antibodies. Further evaluation in an animal model of induced periodontitis is necessary to determine whether the elicited antibodies can effectively inhibit gingipain released by the pathogen. If this vaccine candidate demonstrates protective efficacy, the approach could accelerate and enhance the safety of vaccine design against a wide range of other pathogens.

Suicidal behavior and substance dependence.

Schneider B, Meiländer L, Wetterling T

Adv Clin Exp Med · 2025 Jul · PMID 40708553 · Publisher ↗

Suicidal behavior is a common psychiatric emergency and poses a significant challenge in mental health care. Substance use disorders are among the most frequently observed mental health conditions in individuals who die... Suicidal behavior is a common psychiatric emergency and poses a significant challenge in mental health care. Substance use disorders are among the most frequently observed mental health conditions in individuals who die by suicide.

Genetically determined thyroid function and cerebral cortex structure: A Mendelian randomization study.

Wu X, Liu H, Cui L … +2 more , Mo M, Li C

Adv Clin Exp Med · 2025 Nov · PMID 40699126 · Publisher ↗

BACKGROUND: A correlation between thyroid function and cognitive impairment has been well established; however, the impact of thyroid dysfunction on structural changes in the brain cortex remains largely unexplored. OBJE... BACKGROUND: A correlation between thyroid function and cognitive impairment has been well established; however, the impact of thyroid dysfunction on structural changes in the brain cortex remains largely unexplored. OBJECTIVES: The study describes a 2-sample Mendelian randomization (MR) analysis to elucidate the relationship between thyroid malfunction and brain structure and function. MATERIAL AND METHODS: Eight phenotypes of thyroid function were extracted from THYROIDOMICS consortium by determining free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels in both men and women separately and together, as well as in individuals with increased or decreased TSH levels. The results were assessed in terms of overall brain cortical thickness and the surface area (SA) of grey matter, along with 34 specific measurements for various regions. The primary method employed for the analysis was the inverse-variance weighted (IVW) approach. RESULTS: The data were subjected to MR Egger regression, Cochrane's Q statistic and leave-one-out analysis to determine the correlation between the variables. The FT4 in men, women and overall was statistically associated with cortical thickness of entorhinal cortex (EC). Overall TSH and TSH in men were associated with cortical thickness of caudal anterior cingulate. Additionally, in men, TSH levels showed an association with cortical thickness in the cuneus gyrus. Increased TSH was associated with decreased SA of lateral occipital (LO) and increased SA of lateral orbitofrontal, medial orbitofrontal and superior frontal cortex. Decreased TSH was negatively associated with the SA of pars opercularis (PO) and the cortical thickness of posterior cingulate cortex. No pleiotropy was detected. CONCLUSIONS: Our findings indicate a possible causal link between thyroid function and the cortical architecture of particular functional areas associated with neurodegenerative and psychiatric conditions.

Standardizing clinical evaluations of periodontal condition to guide assessments and diagnoses using the Periodontal Assessment Protocol (GF-PAPro).

Fernandes GVO, Mosley G, Cañizares AC … +2 more , Fernandes JCH, Muller R

Adv Clin Exp Med · 2025 Jul · PMID 40699125 · Publisher ↗

In a highly evolved and developed world, where professionals seek greater knowledge and understanding of advanced surgeries and high technologies, basic concepts have become distant, posing challenges in achieving an acc... In a highly evolved and developed world, where professionals seek greater knowledge and understanding of advanced surgeries and high technologies, basic concepts have become distant, posing challenges in achieving an accurate periodontal diagnosis. Therefore, utilizing a step-by-step clinical and radiographic periodontal assessment protocol can facilitate precise diagnosis. This editorial introduces the Periodontal Assessment Protocol (GF-PAPro), developed based on the most substantial scientific literature, to guide clinicians and experts in standardized clinical periodontal assessments.

Parkin aggravates symptoms of preeclampsia through promoting mitophagy and apoptosis.

Wang L, Wang X, Zheng Y … +4 more , Kong J, Zheng LM, He AH, Chen XJ

Adv Clin Exp Med · 2025 Nov · PMID 40699124 · Publisher ↗

BACKGROUND: Preeclampsia is a serious pregnancy complication with significant maternal and fetal morbidity. Mitophagy plays a crucial role in its pathogenesis. The importance of this study lies in evaluating the role of... BACKGROUND: Preeclampsia is a serious pregnancy complication with significant maternal and fetal morbidity. Mitophagy plays a crucial role in its pathogenesis. The importance of this study lies in evaluating the role of parkin in preeclampsia, which may offer new insights into the management of this disease. OBJECTIVES: This study was designed to evaluate the role of parkin in preeclampsia. MATERIAL AND METHODS: To induce a preeclampsia model, pregnant female rats were administered N-nitro-L-arginine methyl ester (L-NAME) subcutaneously at a dose of 50 mg/(kg·day) starting on gestational day 14 for 7 consecutive days. Uteroplacental tissues were then collected, and chorionic trophoblast cells were isolated. Systolic blood pressure (SBP) and urine protein content were measured on days 12 and 20 of pregnancy. Hematoxylin-eosin (H&E) staining and TUNEL staining were employed to assess pathological changes and apoptosis in uteroplacental tissues, respectively. Reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis were performed to evaluate mRNA and protein expression levels associated with cellular function, mitophagy and the PINK1/parkin signaling pathway. RESULTS: Compared to the negavtive control (NC) group, rats in the model group showed elevated SBP and urine protein levels (p < 0.01). Chorionic trophoblast cells exhibited substantial damage, with significantly increased levels of apoptosis and autophagy. Moreover, parkin mRNA and protein expression levels were markedly upregulated in the model group. Overexpression of parkin in chorionic trophoblast cells enhanced apoptosis and mitophagy, while the autophagy inhibitor 3-methyladenine (3-MA) significantly alleviated the damage caused by overexpression of parkin. CONCLUSIONS: Parkin aggravates the symptoms of preeclampsia by increasing mitophagy and apoptosis.

Association between proinflammatory cytokines and pain intensity in patients with postherpetic neuralgia.

Miao J, Wang L, Feng M

Adv Clin Exp Med · 2025 Nov · PMID 40699123 · Publisher ↗

BACKGROUND: Inflammatory response is involved in the pathogenesis of herpes zoster (HZ) and postherpetic neuralgia (PHN). OBJECTIVES: This study aimed to evaluate levels of proinflammatory factors at different stages of... BACKGROUND: Inflammatory response is involved in the pathogenesis of herpes zoster (HZ) and postherpetic neuralgia (PHN). OBJECTIVES: This study aimed to evaluate levels of proinflammatory factors at different stages of HZ and PHN. MATERIAL AND METHODS: A total of 154 patients within 72 h of HZ onset and 30 healthy controls were included. Patients were followed up to 90 days. The levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) were measured at baseline and 90 days. The visual analogue scale (VAS) was used to assess the intensity of pain and PHN patients were divided into mild-to-moderate pain and severe pain group. RESULTS: Interleukin 6, TNF-α and CRP levels in HZ patients at baseline were significantly higher than in healthy controls and decreased as followed up to 90 days. Moreover, PHN patients had a higher level of IL-6, TNF-α or CRP at baseline and 90 days than non-PHN patients. In addition, PHN patients in the severe pain group had a notably higher baseline or 90-day IL-6, TNF-α and CRP level than in the mild-to-moderate pain group. However, the changes of IL-6, TNF-α and CRP levels between 90 days and baseline were significantly less pronounced in the severe pain group than in the mild-to-moderate pain group. CONCLUSIONS: The levels of proinflammatory cytokines were higher in HZ and PHN patients and associated with pain intensity in PNH patients. These findings suggest that repeated measurements of serum proinflammatory cytokines may aid in clinical management and guide anti-inflammatory treatment strategies.

Effects of echinacoside on the regulation of mitochondrial fission induced by TBK1/Drp1 in rheumatoid arthritis.

Wang X, Chen Z, Wu S … +1 more , Fan X

Adv Clin Exp Med · 2025 Nov · PMID 40600845 · Publisher ↗

BACKGROUND: Dysregulated mitochondrial fission in synovial tissue is a key contributor to the progression of rheumatoid arthritis (RA), and echinacoside (ECH) has been shown to modulate this process in a mouse model of R... BACKGROUND: Dysregulated mitochondrial fission in synovial tissue is a key contributor to the progression of rheumatoid arthritis (RA), and echinacoside (ECH) has been shown to modulate this process in a mouse model of RA. OBJECTIVES: This study aimed to investigate the effects of echinacoside (ECH) on the proliferation and inflammatory response of human fibroblast-like synoviocytes (MH7A cells), and to elucidate the potential underlying mechanisms. MATERIAL AND METHODS: The expression and co-localization of TANK-binding kinase 1 (TBK1) and phosphorylated dynamin-related protein 1 (p-Drp1) in synovial tissues from patients with and without RA were analyzed. MH7A cells were exposed to either ECH or 0.1% dimethyl sulfoxide (DMSO). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) assay and reactive oxygen species (ROS) expression was detected with dichlorofluorescin (DCFH) staining. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), cyclooxygenase (COX)-2, IL-1β, TANK-binding kinase 1 (TBK1), and Drp1 and the oxidative stress markers NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured using quantitative real-time polymerase chain reaction (qPCR). The mitochondrial morphology was detected with transmission electron microscopy (TEM), and the expression levels of p-TBK1 (S172), TBK1, p-Drp1 (S616), p-Drp1 (S637), and Drp1 were assessed using western blotting. RESULTS: Compared to tissue from non-RA patients, RA synovial tissue exhibited higher expression and co-localization of TBK1 and phosphorylated Drp1 (p-Drp1). Following ECH treatment, MH7A cell proliferation and inflammatory cytokine secretion were reduced, while the expression of antioxidant stress markers was significantly increased. Furthermore, ECH treatment led to reduced levels of ROS, mitochondrial fragmentation and dysregulated mitochondrial fission in MH7A cells, along with decreased expression of p-TBK1 (Ser172) and p-Drp1 (Ser616), while p-Drp1 (Ser637) levels were increased. CONCLUSIONS: Echinacoside regulates abnormal mitochondrial fission via the TBK1/Drp1 pathway, reducing the proliferation and inflammatory response of MH7A cells.

Combined CB1 antagonist AM6545 and NOP agonist SCH221510 worsen DSS-induced colitis in mice.

Fabisiak A, Wołyniak MR, Piscitelli F … +5 more , Verde R, Marzo VD, Zielińska M, Machelak W, Małecka-Wojciesko E

Adv Clin Exp Med · 2025 Dec · PMID 40600844 · Publisher ↗

BACKGROUND: Despite the broad range of treatment options available for intestinal inflammation, the development of novel therapeutics remains essential due to the diminishing effectiveness of current therapies over time.... BACKGROUND: Despite the broad range of treatment options available for intestinal inflammation, the development of novel therapeutics remains essential due to the diminishing effectiveness of current therapies over time. Both the endocannabinoid system (ECS) and nociceptin/orphanin FQ peptide (NOP) receptors have been implicated in the pathogenesis of diseases associated with intestinal inflammation, highlighting their potential as therapeutic targets. OBJECTIVES: We hypothesized that an interaction exists between cannabinoid receptors 1 and 2 (CB1 and CB2) and the NOP receptor, which may hold therapeutic relevance for the treatment of colitis. MATERIAL AND METHODS: In this study, we used 3 selective ligands: a CB1 antagonist (AM6545), a CB2 antagonist (AM630) and a NOP agonist (SCH221510) in a mouse model of colitis induced by 3% dextran sulfate sodium (DSS). Quantification of several secondary messengers was conducted using western blot analysis. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess CB1 expression levels in colonic tissue, while liquid chromatography-mass spectrometry (LC-MS) was used to evaluate the concentrations of endocannabinoids and related lipid mediators. RESULTS: We observed a statistically significant increase in the macroscopic score and a nonsignificant increase in the microscopic score in inflamed mice treated with both AM6545 and SCH221510 compared to those treated with SCH221510 alone. Additionally, the combination-treated group exhibited significantly lower levels of extracellular signal-regulated kinases 1/2 (ERK1/2) and significantly higher levels of phosphorylated protein kinase B (p-AKT) and β-arrestin relative to the SCH221510-only group. CONCLUSIONS: Our study offers novel insights into the interaction between the ECS and the NOP receptor, which may inform the development of new therapeutic strategies for inflammatory conditions such as colitis.

New statistical guidelines for manuscripts submitted to Advances in Clinical and Experimental Medicine.

Kujawa K, Bombała W, Kopszak A … +4 more , Wronowicz J, Wuczyński M, Lewandowski Ł, Czapla M

Adv Clin Exp Med · 2025 Jul · PMID 40557957 · Publisher ↗

The updated statistical reporting guidelines for Advances in Clinical and Experimental Medicine (ACEM) streamline the way in which authors describe their statistical analyses and results. In response to the rising popula... The updated statistical reporting guidelines for Advances in Clinical and Experimental Medicine (ACEM) streamline the way in which authors describe their statistical analyses and results. In response to the rising popularity of advanced techniques - such as Bayesian statistics and machine learning - the revisions balance methodological rigor with article readability.

Keratin biomaterials for wound healing and tissue regeneration: A promising approach in biomedical applications.

Konop M

Adv Clin Exp Med · 2025 Aug · PMID 40525647 · Publisher ↗

Keratin biomaterials, derived from natural sources, offer a promising, biocompatible solution for wound healing and tissue regeneration, though further clinical studies are needed to confirm their efficacy. Keratin biomaterials, derived from natural sources, offer a promising, biocompatible solution for wound healing and tissue regeneration, though further clinical studies are needed to confirm their efficacy.

An underrated clinical tool: CBC-derived inflammation indices as a highly sensitive measure of systemic immune response and inflammation.

Geller V, Dominiak M

Adv Clin Exp Med · 2025 Jun · PMID 40525646 · Publisher ↗

This editorial explores the clinical potential of complete blood count-derived inflammation indices (CBC-DIIs) as sensitive and cost-effective measures of systemic inflammation and immune response. This editorial explores the clinical potential of complete blood count-derived inflammation indices (CBC-DIIs) as sensitive and cost-effective measures of systemic inflammation and immune response.

Assessment of physical performance and muscle function in hemodialysis patients participating in an exercise regimen: A cluster-randomized, single-center study.

Rogowski Ł, Kowalska J, Bulińska K … +9 more , Stefańska M, Zembroń-Łacny A, Mahrová A, Marenčáková J, Pawlaczyk W, Gołębiowski T, Wnukiewicz W, Kusztal M, Dziubek W

Adv Clin Exp Med · 2025 Dec · PMID 40497524 · Publisher ↗

BACKGROUND: Many studies reported positive effects of physical exercise on the condition of dialysis patients. The insufficient value of those changes makes it difficult to interpret their clinical relevance. OBJECTIVES:... BACKGROUND: Many studies reported positive effects of physical exercise on the condition of dialysis patients. The insufficient value of those changes makes it difficult to interpret their clinical relevance. OBJECTIVES: This study aimed to assess the influence of selected training (endurance, resistance, tai chi) on cardiopulmonary fitness and muscle function, as well as to analyze the factors having the most significant effect on cardiopulmonary fitness in a group of dialysis patients. MATERIAL AND METHODS: Ninety-eight patients agreed to participate in the study. Selection of the type of training was done by cluster randomization. Group 1 were patients in a cluster with an endurance exercise program, and group 2 in a cluster with resistance exercises. Group 3 consisted of patients who took part in a tai chi program (non-cluster randomization). Exercise programs with each of the 3 groups were conducted for a period of 6 months, 3 times a week (groups 1 and 2) and twice a week (group 3), up to 60 min for 1 session. RESULTS: The full exercises was completed by 45 patients: group 1 - 16; group 2 - 15; group 3 - 14. The significance of the observed difference in the cardiopulmonary function was confirmed only in endurance group for absolute oxygen concumption (VO2) and heart rate (HR). Measurements of peak torque (PTQ) and total work (TW) performed at a speed of 60°/s showed a significant increase in the measured values only in the resistance training group. Measurements of PTQ and TW performed at 180°/s showed a significant increase in the measured values in the endurance and resistance group. CONCLUSIONS: The 6 months of training resulted in a slight improvement in cardiopulmonary parameters only in the endurance group. The above results seem to confirm the observed limited potential for improving aerobic capacity in dialysis patients. The results of strength and speed parameters shows the specificity of each training, expressed by selective improvements in isometric and both isokinetic tests.

Correlations between OCT, OCT angiography and fundus autofluorescence in adults with superficial optic disc drusen: The importance of multimodal imaging.

Szabelska P, Brydak-Godowska J, Krajewski P … +2 more , Różycki R, Gołębiewska J

Adv Clin Exp Med · 2025 Nov · PMID 40474528 · Publisher ↗

BACKGROUND: Optic nerve head drusen (ONHD) are benign calcified deposits that can compress local capillaries, disrupt blood flow and potentially lead to visual loss. OBJECTIVES: The aim of the study was to present the co... BACKGROUND: Optic nerve head drusen (ONHD) are benign calcified deposits that can compress local capillaries, disrupt blood flow and potentially lead to visual loss. OBJECTIVES: The aim of the study was to present the correlations between optical coherence tomography (OCT), OCT angiography (OCTA) results and fundus autofluorescence (FAF) findings in patients with ONHD, and to highlight the importance of multimodal imaging in the diagnosis and management of this pathology. MATERIAL AND METHODS: This retrospective study included 21 patients (36 eyes) with ONHD, with a mean age of 45.75 years (range: 19-71 years), who had no other ocular pathologies. All participants underwent a full ophthalmic examination and multimodal imaging using the DRI Triton OCT (Topcon). Drusen presence was divided into quadrants based on FAF and correlated with OCT and OCTA results. RESULTS: Optic nerve head drusen were unilateral in 6 patients (28.57%) and bilateral in 15 (71.43%). Drusen were most common in the nasal and superior quadrants (NQ and SQ) but were significantly more frequent in the inferior (IQ) and temporal (TQ) quadrants in patients with bilateral ONHD. Eyes with drusen located in the IQ and TQ showed a significantly decreased radial peripapillary capillary (RPCP) vessel density (VD). Retinal nerve fibre layer (RNFL) measurements showed the strongest positive correlations with RPCP, especially in the IQ (r = 0.78, p < 0.001). Ganglion cell layer and nerve fiber layer (GCL++) thickness showed significant correlations with RPCP VD, particularly in the IQ and TQ (p < 0.001 for both). CONCLUSIONS: Fundus autofluorescence is a valuable tool for identifying superficial drusen. Optical coherence tomography and OCTA are effective in assessing optic nerve fiber integrity and microvascular changes. Microcirculation assessment using OCTA should focus not only on the radial peripapillary capillaries (RPCP), but also on the macular region. Multimodal imaging plays a crucial role in the accurate diagnosis and comprehensive evaluation of patients with ONHD. Further longitudinal studies are needed to investigate how these correlations evolve over time, particularly in the context of ONHD progression.

Circular RNA hsa_circ_0008433 drives vascular smooth muscle cell modulation in intracranial aneurysm pathogenesis.

Wang F, Huang QY, Zeng YL … +2 more , Kang XD, Huang Q

Adv Clin Exp Med · 2025 Oct · PMID 40474527 · Publisher ↗

BACKGROUND: Intracranial aneurysm (IA) is a serious condition that can lead to a life-threatening rupture, often resulting in a hemorrhagic stroke. Vascular smooth muscle cell (VSMC) dysfunction is a critical factor in t... BACKGROUND: Intracranial aneurysm (IA) is a serious condition that can lead to a life-threatening rupture, often resulting in a hemorrhagic stroke. Vascular smooth muscle cell (VSMC) dysfunction is a critical factor in the pathogenesis of IA, yet the molecular mechanisms underlying this relationship are not yet fully understood. Recent studies suggest that circular RNAs (circRNAs) are involved in various vascular diseases. High-throughput sequencing identified hsa_circ_0008433 as significantly upregulated in IA tissues, especially in ruptured cases, suggesting a role in IA progression. OBJECTIVES: To further investigate the potential effects of hsa_circ_0008433 on the rupture of human IA. MATERIAL AND METHODS: This study aimed to investigate the effects of hsa_circ_0008433 on IA rupture. We validated the expression of hsa_circ_0008433 in IA patient tissue samples through reverse transcription quantitative polymerase chain reaction (RT-qPCR), comparing ruptured and unruptured aneurysms. Human brain vascular smooth muscle cells (HBVSMCs) were utilized to establish overexpression and knockdown models for hsa_circ_0008433. Cell Counting Kit-8 (CCK-8) and wound healing assays were conducted to assess cell proliferation and migration, while western blotting was employed to measure VSMC phenotype markers including α-smooth muscle actin (α-SMA), smooth muscle protein 22-alpha (SM22α), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). RESULTS: The RT-qPCR analysis confirmed that hsa_circ_0008433 was significantly upregulated in IA tissues, especially in ruptured samples (p < 0.05). Overexpression of hsa_circ_0008433 in HBVSMCs promoted proliferation, migration and phenotype switching, indicated by increased expression of MMPs and decreased contractile proteins. The effects were reversed by the knockdown of hsa_circ_0008433. CONCLUSIONS: We have shown that hsa_circ_0008433 regulates vascular smooth muscle cell function and promotes behaviors that may lead to intracranial aneurysm instability. This study advances the understanding of the role of circRNAs in vascular pathology and identifies hsa_circ_0008433 as a potential therapeutic target for IA. These findings open opportunities for targeted treatments and broader applications in vascular disease research.
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