Mashhad University of Medical Sciences (MUMS) is a medical school in Iran. Located in Razavi Khorasan province in the city of Mashhad, it was established in 1949 with Ferdowsi University of Mashad and separated in 1986 from its parent institution by national legislation.The university is currently ranked as one of the best in the Middle East.[citation needed] In 2001, its department of Medicine was ranked first among the Iranian universities.[citation needed] The latest rankings put Mashhad University in 3rd place nationally.MUMS has 8 faculties, operates 32 hospitals plus 179 rural and 147 urban health care centers. Its faculty include 600 teaching staff, 1700 physicians, 140 dentists, 130 pharmacists, and 25,402 staff employees. In 2001, 7,000 students were enrolled full-time.
Acute ischemic stroke (AIS) analysis from two-dimensional (2D) clinical imaging is hindered by uncontrolled slice tilt and geometric inconsistencies that violate the assumptions of pose-agnostic deep learning (DL) models. This paper proposes a unified geometry-aware, frequency-domain framework for tilted slice localization and ischemic stroke segmentation that explicitly decouples pose estimation from lesion analysis. The method first recovers the full six-degree-of-freedom (6-DoF) rigid pose of arbitrarily tilted slices using frequency-domain slice-to-volume registration, converting a geometrically ill-posed segmentation problem into an anatomically normalized one. Building on this normalization, a frequency-domain segmentation network is introduced that exploits Hermitian symmetry and discriminative spectral bands to enhance sensitivity to ischemic tissue, complemented by a teacher-student knowledge distillation (KD) strategy to improve generalization. Extensive experiments on four public benchmark datasets across multiple imaging modalities demonstrate consistent state-of-the-art (SOTA) performance under controlled geometric variability, with notable improvements on the clinically critical core-penumbra segmentation task and preliminary evidence of robustness to certain domain shifts. The results confirm that explicit geometric modeling combined with spectral-domain analysis provides a robust foundation for medical image segmentation under controlled geometric variability.
Panic disorder (PD) is a psychiatric condition marked by recurring, unexpected panic attacks characterized by intense fear and rapid-onset physiological symptoms. Functional magnetic resonance imaging (fMRI) in individuals with PD has revealed abnormalities in several brain regions associated with fear processing, emotional regulation, and interoception. A systematic search was conducted in PubMed and Embase to review the fMRI changes associated with PD published until April 2024. Eighteen studies were included, primarily employing resting-state fMRI and examining functional connectivity. Consistent findings included amygdala and insula hyperactivity and reduced connectivity within the default mode network, particularly in the posterior cingulate cortex and precuneus. Altered connectivity patterns were also observed in the prefrontal cortex, anterior cingulate cortex, and hippocampus. Task-based fMRI studies revealed increased activity in fear-related regions that correlated with clinical measures of PD severity. This review consolidates the evidence of neural network disruptions in PD, emphasizing dysregulated fear processing, emotional regulation, and self-referential thinking. These findings highlight the potential of fMRI to elucidate the pathophysiology of PD and inform targeted interventions. However, the limited number of available studies, small sample sizes, and methodological heterogeneity, particularly among task-based fMRI studies, warrant cautious interpretation.
Aim This in vitro study compared gingival fibroblast responses to collagen and amniotic membrane (AM) scaffolds, with zinc oxide nanoparticles (ZnO-NPs) and Wharton's jelly mesenchymal stem cell–conditioned medium (WJMSCs-CM). Materials and methods Fibroblasts derived from three donors were cultured on collagen, AM, or AM-ZnO-NPs, with or without WJMSCs-CM. Metabolic activity was assessed using the tetrazolium reduction assay (MTT) at 48 and 72 h. Nuclear distribution was examined qualitatively using 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell–scaffold morphology using field emission scanning electron microscopy (FESEM). Energy-dispersive X-ray analysis assessed elemental composition. Group means and standard deviations were summarized descriptively; conditioned-medium contrasts and the ZnO-by-conditioned-medium contrast within AM were calculated without inferential testing. Results Mean relative MTT signals were higher at 72 h than at 48 h in every group. AM-ZnO-NPs + CM had the highest mean signals: 134.3 ± 12.76% at 48 h and 196.4 ± 4.15% at 72 h. At 72 h, AM, AM-ZnO-NPs, collagen, AM + CM, and collagen + CM yielded 150.3 ± 14.48%, 175.2 ± 9.82%, 144.0 ± 17.47%, 159.8 ± 13.90%, and 150.2 ± 13.54%, respectively. DAPI and FESEM images illustrated nuclear distribution and cell-associated surface morphology, without quantitative proliferation or adhesion measurements. Conclusion AM-ZnO-NPs + CM showed the highest mean metabolic activity under the tested conditions. These descriptive findings support further investigation but do not establish synergy, superior adhesion, or periodontal regenerative efficacy.
Cisplatin remains a cornerstone chemotherapeutic agent for a broad spectrum of solid malignancies; however, the emergence of intrinsic and acquired resistance severely limits its clinical efficacy. Central to the cellular decision between DNA damage repair and apoptosis following cisplatin exposure is the tumor suppressor p53, whose function is tightly governed by its primary negative regulator, Murine Double Minute 2 (MDM2). This review provides a critical synthesis of the molecular interplay within the MDM2/p53 axis and its direct impact on cisplatin sensitivity. We discussed how deregulation of this axis via TP53 mutational inactivation or MDM2 overexpression enables tumor cells to tolerate cisplatin-induced genotoxic stress. Specifically, we analyzed the dual role of MDM2: its E3 ubiquitin ligase activity that targets p53 for proteasomal degradation, and its emerging p53-independent functions in promoting DNA repair fidelity. Furthermore, we evaluated the therapeutic implications of targeting this pathway with small-molecule MDM2 antagonists. We assessed preclinical and clinical evidence supporting the use of MDM2 inhibition to lower the apoptotic threshold and re-sensitize resistant tumors to cisplatin. Therefore, an understanding of the MDM2/p53 feedback loop is essential for optimizing cisplatin-based regimens and developing rational combination therapies to circumvent chemoresistance.
Curcumin, a lipophilic polyphenol widely used in traditional medicine, is the active ingredient in turmeric (Curcuma longa L.). It has various therapeutic effects, such as antitumor potential, due to its interaction with intracellular and extracellular molecules associated with different malignancies. Ceramides are fundamental constituents of cellular membranes that maintain the stability and integrity of cells. Additionally, they have become key signaling agents that govern a spectrum of cellular functions, such as differentiation, proliferation, apoptosis, and cellular senescence. This review primarily introduces ceramides and their metabolism, summarizes their crucial roles in cancer, and categorizes and discusses the mechanisms and pathways through which curcumin could potentially exert its antitumor effects by targeting ceramides. These mechanisms include apoptosis- and autophagy-associated pathways, de novo ceramide generation, and influencing intracellular free calcium levels and acid inhibition. ceramidase, and combinational strategies using various chemical agents, ceramides, or ceramide analogs to enhance curcumin's efficacy. Finally, the review concludes with remarks and prospects for the future of curcumin's antitumor potential in the context of ceramide targeting.
