Background: Mesenchymal stem cells (MSCs) have emerged as a promising strategy for tissue regeneration. Although hypoxia or lipopolysaccharide (LPS) has been shown to affect the regenerative capacity of MSCs, their combined effects on MSCs are still unknown. We examined the effects of hypoxia and LPS on MSC migration rates and paracrine expression.

Materials and Methods: Umbilical cord-derived MSCs (UC-MSCs) were isolated and characterized. Wound scratch assays assessed migration and proliferation under hypoxic conditions, LPS supplementation, or both. The expression of paracrine factors was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Twenty-four hours post-scratching, the gap closure in UC-MSCs after both hypoxia exposure and LPS treatment was significantly enhanced than those in the control group (p=0.008) or those subjected to individual treatments (p=0.028 vs. hypoxia and p=0.0021 vs. LPS). Serum-supplemented media further maximized these synergistic effects. Combined hypoxia and LPS did not affect vascular endothelial growth factor (VEGF) mRNA levels. In contrast, both hypoxia exposure and LPS treatment decreased the transcript levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β).

Conclusion: These findings indicate that the combination of hypoxia and LPS treatment affects the proliferative capacity of UC-MSCs, thus enhancing the MSC migration rate. However, hypoxia and LPS together reduce the expression of paracrine factors in UC-MSCs, potentially attenuating the immunomodulatory efficacy of UC-MSCs in tissue injury microenvironments.

Background: Primary CNS lymphoma (PCNSL) is a rare form of extranodal lymphoma, representing 3 to 4% of brain tumors. We aim to report the clinicopathological features and predictors of survival in patients with PCNSL.

Materials and Methods: This retrospective study was conducted at Shifa International Hospital, Pakistan. Patients diagnosed with PCNSL from 2018 to 2023 were included. The Hans algorithm was used to further categorize cases of high-grade lymphoma. Data were analyzed using IBM® SPSS Statistics Software Version 26.

Results: Fifty-two patients were diagnosed with PCNSL during the study period, out of whom twenty-seven patients had complete clinical and laboratory data available. From these 27 patients, 14 (52%) were male. Mean age was 48.78 ± 13.46 years. Twenty-four (88.9%) patients were immunocompetent and none had HIV infection. On radiology, a solitary lesion was seen in 19 (70.4%) patients with parietal lobe being the most common location in 8 patients. Twenty-six patients were diagnosed with high-grade non-Hodgkin B-cell lymphoma whereas one patient had low-grade non-Hodgkin B-cell lymphoma. Seven patients expired, with median survival of five months (range 1–31 months). Ki-67 proliferative index >80% was the only factor identified as significantly associated with decreased overall survival (p<0.05).

Conclusion: PCNSL is a rare and aggressive disease. High Ki-67 proliferative index is a significant predictor of overall survival in these patients. Lack of association of HIV, frequent occurrence of Bcl6 positivity and a single case of low-grade lymphoma were unique features identified in our study population.

Background: Acute lymphoblastic leukemia is a type of heterogeneous leukemia that is associated with the abnormal proliferation of immature monoclonal B and T lymphoid precursors. Cancer is considered an epigenetic disease due to fundamental changes in the pattern of normal methylation in cancer cells. This study aimed to investigate these changes in 5 candidate genes in childhood B cell-ALL.

Materials and Methods: After blood sampling, DNA extraction, and bisulfite treatment, PCR, and Sanger sequencing were performed for part of the TBX3, SLC38A11, SOX2, KCNQ1, and MAPK1 gene promoter. Finally, the methylation pattern of patients in remission and relapse groups was compared with that of healthy individuals.

Results: In the promoter methylation pattern of MAPK1, a significant difference was observed in the CpG3 site between remission-control and relapse-control groups, and in CpG8, 9, 10 between relapse-control and relapse-remission groups. There was no significant difference in the other 4 genes. 

Conclusion: We reported the similarity of the methylation pattern in the CpG 3 site of the MAPK1 gene promoter in the remission and relapse groups, as well as the difference in the methylation pattern of this location in the two mentioned groups with control groups, which can suggest the methylation pattern in this site as a candidate for a prognostic biomarker. We also reported the similarity of methylation pattern in remission and control groups on CpG 8,9,10 site and significant reduction of methylation in the relapse group compared to both control and remission groups, which can introduce them as a candidate for diagnostic biomarkers.

Background: The production of autoantibodies in cancer patients is a recognized phenomenon, yet their clinical significance and diagnostic yield remain debated. This study evaluated the frequency of rheumatologic autoantibodies in treatment-naïve patients and their association with clinical parameters.

Materials and Methods: In this case-control study, 150 treatment-naïve cancer patients (50 lymphoma, 50 breast cancer, 50 GI cancers) and 150 matched healthy controls were enrolled. A broad rheumatologic panel was performed. Clinical staging and molecular subtyping were recorded, and the 24-month progression-free survival (PFS) was also evaluated in a DLBCL subgroup to assess the prognostic weight of ANA and RF positivity.

Results: ANA and RF positivity were significantly more prevalent in cancer patients (particularly breast and lymphoma) than in controls. However, specific markers (anti-dsDNA, anti-CCP) were almost entirely negative. In lymphoma, aggressive types showed higher numerical autoantibody positivity than indolent forms, though not reaching statistical significance (p‑value <0.05). ANA and RF positivity were not significantly associated with 2-year PFS in the DLBCL subgroup (p > 0.05). In breast and GI cancers, no consistent correlation was found between ANA status and molecular subtypes or histology.

Conclusion: While ANA and RF may be positive in malignancy due to immune dysregulation, these findings are largely non-specific. In the absence of clinical rheumatic symptoms, extensive autoantibody screening does not provide additional diagnostic or prognostic value and should neither prompt a diagnosis of a rheumatic disease nor alter the oncological treatment plan.

Background: Efficient utilization of blood components is a major goal in transfusion medicine, particularly in healthcare systems facing rising demand and limited donor resources. This study evaluated patterns of blood component utilization, return, and expiration in four teaching hospitals in Birjand, South Khorasan, Iran.

Materials and Methods: This multicenter cross-sectional study was conducted over six months (September 2024–March 2025) in hospitals affiliated with Birjand University of Medical Sciences. Data on requests, issuance, transfusion, and return of blood components were extracted from blood bank and hospital information systems. In total, 622 requests and 10,295 issued units were analyzed. Utilization rate, return rate, and crossmatch-to-transfusion (C:T) ratio were calculated. The Kruskal–Wallis test was used to compare return rates among hospitals.

Results: The overall utilization rate was 97.54%, with a return rate of 2.46% and a C:T ratio of 1.05. Significant inter-hospital variability was observed (P < 0.0001). Razi Hospital accounted for 71.3% of returned units (return rate: 6.10%), while Iranmehr Hospital achieved near-complete utilization (0.02%). ICUs and CCUs represented over 75% of returns, and leukocyte-reduced red blood cells were the most frequently returned component (64.5%). A total of 261 units were discarded, mainly due to expiration (74.3%), with B+ showing the highest expiration frequency (19.9%).

Conclusion: Although overall transfusion efficiency was high, substantial variability in return and expiration patterns suggests that targeted, data-driven interventions may further reduce wastage and improve patient safety.

Background: Breast cancer and its treatments significantly impair patients’ health-related quality of life (HRQoL). Spiritually oriented interventions, such as Dhikr therapy — the rhythmic recitation of Islamic holy words and phrases — aim to promote physiological and psychological relaxation. Although such approaches have shown promise in improving quality of life, evidence on structured, group-based Dhikr programs in oncology populations remains limited. This study aimed to evaluate the effectiveness of a six-session group-based Dhikr therapy program on HRQoL in women with breast cancer.

Materials and Methods: This two-arm, parallel-group randomized controlled trial included 60 women aged 25–55 years with confirmed breast cancer. Participants were randomly allocated (1:1) to either the intervention group (n=30), which received a structured 6-week group-based Dhikr therapy, or the control group (n=30), which received standard oncology care. The intervention consisted of weekly 90-minute sessions incorporating Quranic reflection, gratitude practice, guided visualization, and facilitated group sharing. The primary outcome was HRQoL, assessed using the EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and within one week after intervention completion. The trial was registered with the institutional ethics committee (IR.SBMU.CRC.REC.1403.005). Statistical analysis was performed using SPSS v.31. Continuous data are presented as mean ± SD and categorical data as frequencies (%). Group differences were assessed with independent t-test, Mann–Whitney U, and chi-square tests as appropriate. Intervention effects on HRQoL were analyzed by two-way repeated-measures ANOVA. Significance was set at P ≤ 0.05.

Results: Compared with the control group, women in the Dhikr therapy group showed statistically significant improvements in all domains of the QLQ-C30: Symptom subscale (mean change: −17.40 vs. +9.38; P < 0.001), Function subscale (+9.58 vs. −20.08; P < 0.001), Single Items subscale (a global symptom index; −14.26 vs. +9.08; P < 0.001), and total score (intervention: 53.89 ± 32.51 to 75.83 ± 19.25; control: 70.28 ± 22.07 to 52.22 ± 16.07; P < 0.001). Similarly, the intervention group demonstrated significant improvements in the QLQ-BR23: Symptom subscale (−10.97 vs. +5.14; P = 0.001) and Function subscale (+15.41 vs. −32.91; P = 0.001), while the control group showed deterioration in both subscales.

Conclusion: A structured, group-based Dhikr therapy program improved both general and breast cancer-specific HRQoL among women with breast cancer. These findings support the integration of culturally appropriate spiritual interventions into standard supportive oncology care.

Disorders of the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, cerebral palsy, stroke, and spinal cord injury, are associated with neuronal damage, neuronal loss, inflammation, and impaired neurological function and remain major challenges in medicine. Despite advances in pharmacological, surgical, and rehabilitative interventions, many of these disorders lack definitive or fully effective treatments. In recent years, stem cell-based therapies have received considerable attention as potential approaches for neural repair and functional recovery. Mesenchymal stem cells (MSCs) have attracted particular interest because of their distinctive biological properties, including their capacity for differentiation, secretion of neurotrophic factors, immunomodulatory and anti-inflammatory effects, and migration toward injured tissues. Compared with other stem cell types, including neural stem cells, embryonic stem cells, and induced pluripotent stem cells, MSCs offer several potential advantages, such as relatively easy accessibility, availability from multiple sources, including bone marrow, adipose tissue, and umbilical cord blood, and fewer ethical concerns. This narrative review examines published studies on the application of MSCs in neurological disorders, with particular emphasis on their biological characteristics, potential mechanisms of action, cellular sources, and advantages compared with other stem cell types. The available evidence regarding the use of MSCs in neurodegenerative diseases and other CNS disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, and spinal cord injury, is also reviewed and discussed. Overall, available evidence suggests that MSCs may support neural function and repair through neurotrophic, anti-inflammatory, immunomodulatory, and regenerative mechanisms. However, despite encouraging findings from preclinical studies and some clinical investigations, current clinical evidence remains limited and heterogeneous. Differences in cell source, cell preparation and administration, dosage, treatment timing, and long-term outcomes may influence therapeutic effects. Therefore, well-designed and adequately powered clinical studies are needed to establish the efficacy and safety of MSC-based therapies and to determine their potential advantages over other cell-based approaches.

Cytomegalovirus (CMV) infection is one of the most important causes of mortality and morbidity in hematopoietic stem cell transplant (HSCT) recipients. There are many guidelines for CMV prevention, diagnosis, and treatment. However, in resource-limited settings, the implementation of international guidelines is constrained by some differences in epidemiology, diagnostic methods, and drug availability. This study develops a national guideline for CMV management based on the healthcare context in Iran. The Guideline Development Group (GDG) is a multidisciplinary team that consists of experts in hematology, oncology, infectious diseases, virology, pharmacology, epidemiology, and methodology that develops the guideline. To have a systemic approach, a literature review was conducted based on relevant studies about CMV management in HSCT recipients from 2000 to 2025. The quality of evidence is assessed through the GRADE methodology and Delphi process. The guideline includes recommendations for risk stratification, surveillance, diagnostic methods, prophylactic strategies, and management of resistant/refractory infections. However, considering limited access to anti-viral agents such as Letermovir in Iran, alternative approaches are designed to have a feasible and effective protocol. Therefore, the guideline integrates international evidence with local healthcare real settings to provide an implementable protocol for CMV management. The context-adapted guideline results in optimized resource utilization and reduces variability in practice. Considerably, the establishment of a national registry system and periodic updates can strengthen CMV control in Iran healthcare system.

Hair loss is a commonly encountered condition that often causes significant distress with diverse etiologies, including androgenic, autoimmune, inflammatory, and aging-related mechanisms. Current therapeutic options, such as minoxidil and finasteride, often exhibit limited efficacy and are associated with adverse effects, necessitating the exploration of safer and more effective alternatives. This review aims to explore the therapeutic potential of mesenchymal stem cell (MSC)-derived secretome as a novel cell-free approach for hair restoration. A narrative review of recent preclinical, in vivo, and early clinical studies was conducted to evaluate the role of MSC-secretome components, including growth factors, cytokines, extracellular vesicles, and exosomes, in modulating key pathways involved in the regeneration of hair follicles. In vitro and ex vivo models demonstrate that MSC-secretome enhances the proliferation, migration, and survival of dermal papilla cells and hair follicle stem cells by activation of the Wnt/β-catenin, IGF-1, VEGF, and PI3K/AKT signaling pathways via paracrine signaling. In vivo animal models of alopecia indicate accelerated anagen initiation, follicle reactivation, improved dermal papilla function, and reduced inflammatory mediators following treatment with MSC-conditioned medium or exosomes. Early clinical evidence, including topical MSC-conditioned medium application in alopecia areata, suggests improved follicular density and hair shaft thickness without significant adverse effects. In conclusion, MSC-derived secretome represents a promising, cell-free strategy for hair regeneration. Future research should prioritize optimizing production protocols, standardizing active components, validating potency assays, addressing regulatory and manufacturing challenges, and conducting well-designed clinical trials to ensure consistent therapeutic outcomes.

None

Common variable immunodeficiency (CVID) is the most common antibody deficiency in adults and is frequently associated with autoimmune conditions. One such condition is autoimmune hemolytic anemia (AIHA), an acquired blood disorder that can be the initial manifestation of CVID. Additionally, patients may develop granulomatous and lymphoproliferative lung disease (GLILD), a serious complication that worsens prognosis and requires early recognition. We describe a 25-year-old man with AIHA who had a severe hemolytic crisis and persistent anemia despite optimal immunomodulatory therapy. Infectious diseases, other autoimmune disorders and neoplasms were ruled out. In further studies, marked hypogammaglobulinemia of IgG, IgA, IgM and IgE was documented, confirming the diagnosis of CVID as the underlying cause of his refractory AIHA. During hospitalization, the patient developed a spontaneous pneumothorax with associated pulmonary micronodules, raising a strong suspicion of GLILD. This case illustrates that CVID may initially present as apparently isolated AIHA and remain unrecognized until serious complications emerge. Measurement of serum immunoglobulin levels should be considered in patients with atypical or treatment-refractory AIHA, recurrent infections, or accompanying lymphoproliferative features, as early recognition of CVID enables timely IVIG replacement and monitoring for associated complications.

Doxorubicin extravasation is a rare but serious complication of chemotherapy that may result in progressive soft tissue injury and necrosis. Dexrazoxane is currently the only approved antidotal therapy for anthracycline extravasation; however, its availability may be limited in some healthcare settings. We report the case of a woman in her 40s with diffuse large B-cell lymphoma who developed peripheral doxorubicin extravasation during the first cycle of R-CHOP chemotherapy administered through a peripheral intravenous cannula. The event was recognized immediately, and standard management, including cessation of the infusion, attempted aspiration of the extravasated drug, limb elevation, and application of intermittent cold compresses, was initiated. Because dexrazoxane was unavailable, the patient was managed with close clinical monitoring and conservative wound care, including topical dimethyl sulfoxide and hydroactive dressings. The lesion progressed to superficial ulceration without evidence of deep tissue necrosis. Serial clinical examinations and Doppler ultrasonography excluded vascular compromise. Complete epithelialization was achieved within approximately 6 weeks without surgical intervention. Although dexrazoxane remains the standard treatment for anthracycline extravasation, this case suggests that favorable outcomes may be achieved in carefully selected patients through structured conservative management and close multidisciplinary follow-up when the antidote is unavailable. Nevertheless, conservative management should not be considered a substitute for guideline-recommended antidotal therapy when dexrazoxane is accessible.