Category: Statistics

Curr Issues Mol Biol. 2025 Apr 26;47(5):306. doi: 10.3390/cimb47050306.

ABSTRACT

The objectives of this study comprise the identification of key miRNAs and their target genes associated with severe tolerance in individuals exposed to aluminum and welding fumes, and the elucidation of the underlying regulatory mechanisms. In this study, the levels of seven miRNAs (hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-25-3p, hsa-miR-363-3p, hsa-miR-92a-3p, hsa-miR-24-3p, and hsa-miR-19b-3p) were analyzed using both hsa-miR-16-5p and RNU6 (U6 snRNA) as reference miRNAs to validate normalization reliability. The qRT-PCR method was used on blood serum samples from 16 workers who were exposed to aluminum, 16 workers who were exposed to welding fumes, and 16 healthy controls who were not exposed to aluminum or welding fumes. We determined heavy metal levels from serum samples of workers exposed to aluminum and welding fumes and control groups using the ICP-OES method. The expression levels of hsa-miR-19a-3p and hsa-miR-19b-3p in aluminum-exposed and control groups were found to be statistically significant (p < 0.05). When workers exposed to welding fumes were compared with the those in the control groups, the expression levels of hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-92a-3p, and hsa-miR-24-3p were observed to be statistically significant (p < 0.05). This study shows that the identification of miRNAs and target genes in different biological functions and pathways plays an important role in understanding the molecular mechanisms of responses to heavy metal toxicity. We share the view that the study will make a significant contribution to the literature in that seven candidate miRNAs can be used as possible biomarkers for exposure to aluminum and welding fumes in humans.

PMID:40699705 | DOI:10.3390/cimb47050306

Curr Issues Mol Biol. 2025 Apr 11;47(4):271. doi: 10.3390/cimb47040271.

ABSTRACT

BACKGROUND: This case-control study investigates whether miR-27a rs895819 A>G polymorphism is associated with an increased risk of recurrent pregnancy loss (RPL) in Caucasian Greek women.

METHODS: This study included 93 women with at least two unexplained miscarriages before the 24th week of gestation (RPL group) and 107 women with no pregnancy loss history (control group). The miR-27a rs895819 A>G polymorphism was detected using PCR amplification, followed by DraIII-HF restriction enzyme digestion.

RESULTS: The GG genotype was linked to a significantly higher risk of RPL (p-value = 0.00005), whereas the AA genotype was associated with a significantly lower risk (p-value = 0.00036). The AG genotype appeared more frequently in women with RPL (49.5% vs. 44.9% in controls), but the difference was not statistically significant (p-value = 0.5139).

CONCLUSIONS: To our knowledge, this is the first study demonstrating that the miR-27a A>G polymorphism was significantly associated with a higher risk of recurrent miscarriage in Caucasian women. These findings provide evidence that the GG genotype may serve as a potential genetic marker for identifying women at higher risk of recurrent miscarriage, offering valuable insights for genetic counseling and reproductive medicine.

PMID:40699670 | DOI:10.3390/cimb47040271

Curr Issues Mol Biol. 2025 Apr 9;47(4):266. doi: 10.3390/cimb47040266.

ABSTRACT

Current research discusses the putative importance of RNA modification in tumor diseases. These RNA modifications include predominantly pseudouridinylation, ortho-methylations on the ribose residues, as well as methylations on the organic bases. Such chemical modifications directly influence fundamental properties such as transcript stability, alternative splicing, and translation efficiency, all of which are basic requirements for (tumor) cell proliferation, cell metabolism, cell migration, apoptosis resistance, etc. In this comparative study, the two RNA-modifying factors, pseudouridine synthase 7 (PUS7, RNA pseudouridinylation) and WT1-associated protein (WTAP, m6A RNA methylation), were identified using data from human renal cell carcinoma (RCC) tumors. PUS7 and WTAP showed a statistically significant correlation with relevant proliferation and prognosis markers such as CXCR4, TP53, PTEN, and NRAS, as well as with the two tumor immune checkpoints HLA-G and LGALS9 and were directly associated with a statistically significant effect on overall survival. Furthermore, comparative analyses also identified further putative target mRNAs of importance for tumor biology of PUS7 and WTAP. In particular, components with direct relevance for mitosis, the cell cycle, and cell division, as well as the WNT pathway, were identified.

PMID:40699665 | DOI:10.3390/cimb47040266

Curr Issues Mol Biol. 2025 Apr 7;47(4):255. doi: 10.3390/cimb47040255.

ABSTRACT

Kidney transplantation is the preferred treatment for chronic kidney disease, significantly improving patient survival and quality of life. After the procedure, there is a gradual tendency to normalize most of the physiological and metabolic processes, but the need for immunosuppression may lead to new disorders related to the drugs’ side effects and changes in proportions of body composition. The aim of the study was to analyze the concentrations of adipocytokines such as leptin, adiponectin, visfatin, and resistin, and to assess the body composition in patients with stabilized kidney graft function treated with tacrolimus, mycophenolate mofetil, and glucocorticosteroids. A total of 47 participants were enrolled, including 25 kidney transplant recipients on uniform immunosuppressive therapy and 22 healthy controls. The concentrations of leptin, adiponectin, and IL-6 in kidney transplant recipients was significantly higher than in the control group (p = 0.014, p = 0.031, p = 0.000, respectively), while the other adipocytokines, such as visfatin and resistin, do not obtain statistically significant differences. The bioelectrical impedance analysis showed statistically significant differences for fat-free mass index (p = 0.027), visceral fat area (p = 0.023), waist circumference (p = 0.006), fat mass (p = 0.028), and fat mass index (p = 0.034), all of which had higher mean values in the study group. Preliminary findings suggest that kidney transplantation leads to significant alterations in adipocytokines levels, with potential implications for metabolic health.

PMID:40699654 | DOI:10.3390/cimb47040255

Curr Issues Mol Biol. 2025 Mar 28;47(4):236. doi: 10.3390/cimb47040236.

ABSTRACT

BACKGROUND: Our aim was to assess the expression profiles of the messenger RNA (mRNA) expression profiles of stem-cell genes (POU5F1, NANOG) and pancreatic progenitor genes (CK19, HES1, INS, PDX1) in peripheral-blood mononuclear cells (PBMCs) in selected neoplastic pancreatic diseases, such as cancer and neuroendocrine tumors, to identify neoplastic disease markers in the pancreas.

METHODS: In this study, 49 patients diagnosed with pancreatic neoplastic diseases (37 with cancer and 12 with neuroendocrine tumors) and 34 control patients, all of whom were hospitalized at a tertiary center, were enrolled. Venous blood samples were collected from the participants, and RNA was extracted from PBMCs. The mRNA expression levels of six stem-cell and pancreatic progenitor markers- POU5F1 (POU class 5 homeobox 1), NANOG, CK19 (keratin 19), HES1 (HES family bHLH transcription factor 1), INS (insulin), and PDX1 (pancreatic and duodenal homeobox 1)-were quantified via real-time quantitative PCR. The data were statistically analyzed to explore associations between gene-expression levels and various clinical, biochemical, and morphological parameters (including full blood count, Ca 19-9, weight, height, and BMI) via the Kruskal-Wallis test, Mann-Whitney U test, and Spearman rank correlation coefficient.

RESULTS: The results revealed that the expression of the gene associated with early stem cells, NANOG (median= 0.002, p = 0.03), as well as the genes encoding insulin INS (median = 0.004, p = 0.02) and CK19 (median 0.0003, p = 0.005), was significantly elevated in patients with pancreatic cancer. However, the gene-expression levels in patients with neuroendocrine tumors did not exhibit statistically significant differences compared to those observed in the control group. Additionally, no significant differences in gene expression were observed among patients at different stages of pancreatic cancer. Furthermore, CK19 overexpression was found to be positively correlated with inflammatory markers, specifically C-reactive protein (CRP) and WBC, in patients with pancreatic cancer.

CONCLUSIONS: An elevated mRNA expression of specific stem and pancreatic progenitor genes (NANOG, INS, CK19) in PBMCs may serve as a potential markers for pancreatic cancer, reflecting the disease’s interplay with systemic inflammation.

PMID:40699634 | DOI:10.3390/cimb47040236

Curr Issues Mol Biol. 2025 Mar 27;47(4):231. doi: 10.3390/cimb47040231.

ABSTRACT

Mesenchymal stromal cells (MSCs) influence tumor biology and immunology by releasing cytokines, chemokines and growth factors. Currently, cisplatin is an integral part of drug-based tumor therapy, for example, in head and neck squamous cell carcinoma (HNSCC). Cisplatin treatment induces apoptosis as a primary mechanism of action; however, additional immunomodulatory effects of cisplatin are gaining interest. The aim of this study is to evaluate the possible immunomodulatory effects of cisplatin in human MSCs (hMSCs). The MSCs, obtained from human bone marrow, were characterized by analyzing plastic adherence, typical surface features, and ability to differentiate. Toxicity analysis of cisplatin’s effects on primary MSCs, including the determination of a subtoxic concentration, was performed using the MTT assay. Enzyme-linked immunosorbent assays (ELISA) and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify potentially immunomodulatory factors. Additionally, a scratch assay was performed to evaluate cell migration. First, subtoxic cisplatin concentrations were determined. A significantly reduced protein expression of indoleamine 2,3-dioxygenase 1 (IDO1) in MSCs under the influence of subtoxic cisplatin concentrations was demonstrated. Similarly, IL-6 protein expression was qualitatively reduced at subtoxic concentrations, although without statistical significance. At the mRNA level, qRT-PCR showed a non-significant, cisplatin concentration-dependent reduction in the expression of both IL-6 and IDO1. The scratch assay showed no statistically significant influence on migration after cisplatin treatment. In MSCs, there is tendency to a decrease in IL-6 and IDO1 at both protein and mRNA level after cisplatin exposure. These effects are congruent with each other and dose-dependent. This indicates that cisplatin not only acts via the known cytotoxic effect, but may induce a reduction in tumor-supporting proteins, like IL-6 and IDO1, by MSCs in the tumor microenvironment at subtoxic concentrations. Traditional cytostatic compounds, which can favorably modulate the immune system in the tumor microenvironment, may open new avenues to explore treatment strategies specifically targeting immunomodulation. Overall, the results indicate beneficial immunomodulation by cisplatin.

PMID:40699630 | DOI:10.3390/cimb47040231

Curr Issues Mol Biol. 2025 Mar 26;47(4):228. doi: 10.3390/cimb47040228.

ABSTRACT

The aim of this research was to provide a comparative analysis of the major parameters of the blood lipid spectrum found both in the case of brain tumors and in atherosclerosis, as well as to assess the correlation of these indicators with the proliferative activity index Ki-67 in cells. Blood analyses were conducted on samples from 50 patients with brain tumors and 50 patients with cerebral atherosclerosis. Blood plasma from 50 essentially healthy people was used for controls. Significant differences were found in the parameter values between the atherosclerosis sufferers and the control group only for their ratios of neutral lipids to cholesterol. Of the short-chain fatty acids, butyric acid is of greatest interest due to the significant differences of its levels from the control group in the blood of both patients with meningiomas and of those with gliomas. Statistically significant correlation coefficients between the levels of the Ki-67 cell proliferation marker and, in particular, butyric acid were found when compared with the neutral lipids to cholesterol ratios. These identified parameters of the blood plasma lipid spectrum can be used for preoperative diagnostics of brain tumors. However, these ratios cannot be used as preoperative noninvasive predictors of the level of the Ki-67 mitotic index, as no significant differences corresponding to this were found for low-grade or for high-grade anaplasia of brain tumors.

PMID:40699627 | DOI:10.3390/cimb47040228

Curr Issues Mol Biol. 2025 Mar 21;47(4):216. doi: 10.3390/cimb47040216.

ABSTRACT

High heterogeneity of breast cancer is due to a large variety of cancer cell characteristics at the genomic, epigenomic, transcriptome, and proteomic levels. One of the difficulties is the separation of molecular biological subtypes based on the expression of tumor markers. Another problem is the difficulty of venipuncture in cancer patients when taking blood at different stages of patient care. Objectives: To identify statistically significant changes in the level of salivary tumor markers depending on the molecular biological subtype of breast cancer in order to improve understanding of the individual properties of each of its subtypes, 140 volunteers (breast cancer-110; healthy control-30) took part in the case-control study. Saliva was collected strictly before the start of treatment, and the content of ten tumor markers was determined by ELISA: EGFR2, CA15-3, CA27.29, MCA, CEA, CA125, CA19-9, CYFRA 21-1, ferritin, and CRP. The content of MUC1 antigens (CA15-3, CA27.29, and MCA) statistically significantly decreased in the luminal B(+) subtype of breast cancer. The CA19-9 antigen showed high sensitivity to low HER2 expression. A reliable increase in the level of CYFRA 21-1 in saliva was shown in luminal A and luminal B(-) breast cancer. The work demonstrates the diagnostic capabilities of saliva in measuring tumor markers in patients with breast cancer. It was also found that there are reliable differences in the expression level and set of tumor markers in saliva depending on the molecular biological subtype of breast cancer. Thus, CYFRA 21-1 significantly increases with luminal A and luminal B(-), but CRP only increases with luminal A. CA15-3, CA27.29, MCA, and CA19-9 significantly decrease with luminal B(+) breast cancer.

PMID:40699615 | DOI:10.3390/cimb47040216

Int J Oral Maxillofac Implants. 2025 Jul 23;0(0):1-26. doi: 10.11607/jomi.11144. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to compare the peri-implant bone surrounding a new abutment free tissue-level implant design with classic tissue-level implants restored with titanium-base abutments.

MATERIALS AND METHODS: A retrospective cohort study was conducted between 2018 and 2022 in patients requiring dental implants. A total of 53 patients received either a novel abutment-free tissue-level implant (n₁ = 50 sites) or a conventional tissue-level implant (n₂ = 50 sites). Patients were monitored for one year after prosthetic loading, with the primary endpoint being any change in hard tissue around the implant. Bone resorption was evaluated using cone beam computed tomography (CBCT). Statistical analyses included Fisher’s exact test for categorical variables and Student’s t-test for continuous variables. Longitudinal outcomes were assessed using linear mixed models to account for within patient correlations over time. The models incorporated treatment group, time, and their interaction, with statistical significance evaluated using Wald tests. Non-inferiority was assessed with one-sided p-values <0.025, while two-sided p-values <0.05 indicated statistical significance.

RESULTS: No significant differences in patient demographics or complications were found between abutment-free and conventional implants. However, abutment-free implants exhibited less buccal bone loss than traditional implants. The abutment-free implant group had significantly lower buccal bone loss (p-values of 0.025 and 0.024 for oral palatal/lingual bone and alveolar ridge width, respectively).

CONCLUSION: The results of this study suggest that abutment-free dental implants offer advantages in reducing buccal bone loss compared to conventional implants, potentially due to their ability to mitigate risks to peri-implant tissues. Further research is warranted to evaluate their long-term efficacy and safety.

PMID:40699608 | DOI:10.11607/jomi.11144

JAMA. 2025 Jul 23. doi: 10.1001/jama.2025.11178. Online ahead of print.

ABSTRACT

IMPORTANCE: Cognitive behavioral therapy (CBT) skills training interventions are recommended first-line nonpharmacologic treatment for chronic pain, yet they are not widely accessible.

OBJECTIVE: To examine effectiveness of remote, scalable CBT-based chronic pain (CBT-CP) treatments (telehealth and self-completed online) for individuals with high-impact chronic pain, compared with usual care.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness, 3-group, phase 3 randomized clinical trial enrolled 2331 eligible patients with high-impact chronic musculoskeletal pain from 4 geographically diverse health care systems in the US from January 2021 through February 2023. Follow-up concluded in April 2024.

INTERVENTIONS: Participants were randomized 1:1:1 to 1 of 2 remote, 8-session, CBT-based skills training treatments: health coach-led via telephone/videoconferencing (health coach; n = 778) or online self-completed program (painTRAINER; n = 776); or to usual care plus a resource guide (n = 777).

MAIN OUTCOMES AND MEASURES: The primary outcome was attaining or exceeding the minimal clinically important difference (MCID) in pain severity score (≥30% decrease; score range, 0-10) on the 11-item Brief Pain Inventory-Short Form from baseline to 3 months; 6 and 12 months from baseline were secondary time points. Secondary outcomes at 3, 6, and 12 months included pain intensity, pain-related interference, PROMIS (Patient-Reported Outcomes Measurement Information System) social role and physical functioning; and patient global impression of change.

RESULTS: Among 2331 eligible randomized individuals (mean age, 58.8 [SD, 14.3] years; 1712 [74%] women; 1030 [44%] rural/medically underserved), 2210 (94.8%) completed the trial. At 3 months, the adjusted percentage of participants achieving 30% or greater decrease in pain severity score was 32.0 (95% CI, 29.3-35.0) in the health coach group, 26.6 (95% CI, 23.4-30.2) in the painTRAINER group, and 20.8 (95% CI, 18.0-24.0) in the usual care group. Both intervention groups were significantly more likely to attain an MCID in pain severity compared with control (health coach vs usual care: relative risk [RR], 1.54 [95% CI, 1.30-1.82]; painTRAINER vs usual care: RR, 1.28 [95% CI, 1.06-1.55]), and the health coach program was more effective than the online self-completed painTRAINER program (health coach vs painTRAINER: RR, 1.20 [95% CI, 1.03-1.40]). Statistically significant benefits were observed for both intervention groups vs usual care at 6 and 12 months after randomization for the pain severity outcomes and for other secondary pain and functioning outcomes.

CONCLUSIONS AND RELEVANCE: Remote, scalable CBT-CP treatments (delivered either via telehealth or self-completed modules online) resulted in modest improvements in pain and related functional/quality-of-life outcomes compared with usual care among individuals with high-impact chronic pain. These lower-resource CBT-CP treatments could improve availability of evidence-based nonpharmacologic pain treatments within health care systems.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523714.

PMID:40699570 | DOI:10.1001/jama.2025.11178