Salinity and drought stresses induced by climate change pose critical threats to global food security, necessitating a comprehensive insight of plant adaptive mechanisms at the genomic level. This review brings together recent advances in identifying genes, regulatory networks, and evolutionary strategies underlying plant responses to osmotic stress. We discuss key transcription factor families (DREB, NAC, MYB, and WRKY), ion transporters (SOS pathway, NHX, and HKT), genes involved in osmolyte biosynthesis, and reactive oxygen species (ROS) scavenging systems. Recent genomic studies have revealed extensive expansions of gene families, neofunctionalization events, and convergent evolution across plant lineages. Multiomics integration has illuminated complex regulatory networks involving microRNAs, long noncoding RNAs (lncRNAs), and epigenetic modifications that fine-tune stress responses. We examine natural variation in stress tolerance, highlighting genomic signatures of selection in halophytes and xerophytes that provide insights for crop improvement. Pangenomic analyses revealed that significant structural variations and presence-absence variations contributed to stress adaptation. Finally, we discuss evolutionary trade-offs, the impact of domestication on stress resistance, and future directions for leveraging genomic knowledge through precision breeding, gene editing, and systems biology approaches to develop climate-resilient crops.
The genetic hallmark of Acute promyelocytic leukemia (APL) is the balanced reciprocal translocation t(15;17)(q24;q21), resulting in the PML::RARα fusion gene. Although the majority of APL patients carry the typical t(15;17), variant translocations involving three or more chromosomes have also been described. We report a case of a 59-year-old man showing clinical, morphologic, laboratory, and immunophenotypic findings of APL. Cytogenetic analysis revealed a variant complex 4-point break-three-way translocation involving chromosomes 8p, 15q and 17q. Dual-color dual-fusion fluorescence in situ hybridization (D-FISH) analysis showed a typical pattern with two PML::RARα fusion signals, one on the derivative chromosome 17 and one on the derivative chromosome 8. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) for PML::RARα transcripts was negative. These results illustrate the usefulness of combining cytogenetic and molecular analysis to identify the PML::RARα fusion gene in all cases with strong suspicion of APL.
Acute myeloid leukemia (AML) represents a clinically and genetically heterogeneous group of hematologic malignancies. Among the less frequently encountered cytogenetic abnormalities are jumping translocations (JTs), in which a segment from a donor chromosome relocates to multiple recipient chromosomes. Although uncommon, these events have been described in association with clonal evolution and, in some cases, more aggressive disease behavior. Here, we describe a 49-year-old man who presented with fatigue and generalized weakness and was subsequently diagnosed with AML harboring an inv(16)(p13.1q22)/CBFB::MYH11 rearrangement. In addition to the primary leukemic clone, cytogenetic evaluation identified three sideline clones demonstrating a jumping translocation involving chromosome 11 with the breakpoint at band 11q13. The 11q13 segment was observed on different recipient chromosomes, namely 16p13.1, 19p13.3, and 21q22, indicating a notable degree of clonal heterogeneity. While AML with inv(16) is typically associated with a favorable prognosis, the concurrent presence of a chromosome 11q13 jumping translocation in this case suggests added biological complexity. Such secondary cytogenetic changes may have implications for disease evolution and risk stratification. This case underscores the importance of integrating conventional cytogenetic analysis with next-generation sequencing to delineate clonal architecture better and support clinical decision-making in AML.
Cancer remains one of the major global challenges due to its complex and heterogeneous molecular nature across individuals. Recent advances in technology have enhanced the understanding of cancer’s molecular mechanisms, paving the way for the development of effective therapeutics. These include small-molecule inhibitors and monoclonal antibodies, used to interfere with the oncogenic signaling pathways. Immunotherapy has also emerged as a promising area in cancer therapy, with approaches such as immune checkpoint inhibitors, immune cell engagers, adoptive T-cell therapies, and cancer vaccines. Besides, stem cell-based approaches are also being assessed for their potential to modulate immune responses and promote tissue repair. Although these advances have improved cancer care, significant challenges remain. The major challenges in cancer therapy may include drug resistance, side effects, and systemic toxicity that diminish therapeutic efficacy. Moreover, the heterogeneous nature of tumors and the immunosuppressive tumor microenvironment (TME) in solid tumors further complicate treatment responses, especially in advanced or aggressive cancers. Hence, in this review, we highlight the latest approaches in cancer therapy and discuss the remaining gaps and challenges that hinder their full clinical potential.
Hereditary Cardiomyopathies (HCs) are defined as genetically determined cardiovascular diseases (CVDs) that frequently exhibit a familial inheritance pattern. These conditions include cardiomyopathies (CMs), arrhythmias (ARs), and other inherited cardiovascular syndromes. In Panama, the national incidence of Hereditary Cardiomyopathies remains unknown. The objective was to identify genetic variants in Panamanian patients diagnosed with HCs or cardiac arrhythmias and subsequently to identify carrier families to provide genetic counseling. This was an observational, descriptive, cross-sectional study. Patients clinically diagnosed with HCs or ARs were referred from various cardiology and pediatric services between 2019 and 2023. Next-Generation Sequencing (NGS) was performed using a targeted panel of 128 associated genes. The sequencing was conducted on the Illumina MiniSeq platform using a capture-based technology assay. The sample consisted predominantly of patients from urban areas, with no ethnic distinctions made due to the high degree of genetic admixture characteristic of the country’s population. 91 patients were included, presenting with CM (75 cases), AR (12 cases), or both (11 cases). The overall diagnostic yield was 21% (17/81) for cardiomyopathies and 26.1% (6/23) for arrhythmias. In CM cases, all patients with identified Pathogenic (P) or Likely Pathogenic (LP) variants also had a confirmed family history of the disease. Conversely, CM patients without a family history only presented Variants of Uncertain Significance (VUS) or negative results. In AR cases, P/LP variants were identified in four patients with a family history and in two without. The study also reported the identification of four novel pathogenic genetic variants in the FLNC, TTN, DSC2, and LAMA4 genes. The identification of P/LP genetic variants associated with HCs in the Panamanian population has facilitated appropriate genetic counseling for affected families and enabled the active screening and identification of asymptomatic carriers within these high-risk lineages, which is essential for early intervention and prevention strategies.
Congenital factor VII (FVII) deficiency is the most common rare bleeding disorder (RBD), presenting with various clinical manifestations. Given the heightened risk of life-threatening bleeding and fatal hemorrhagic complications, prompt detection of the disorder is critical, especially in cases with low FVII levels and a history of familial severe clinical presentations. In such cases, prenatal diagnosis (PND) emerges as a life-saving option. In this study, we reported two PNDs in a family with a positive family history of severe FVII deficiency (<1%) and a positive history of breast cancer in the mother at the time of the second PND. Sanger sequencing of the entire F7 gene was performed to detect the underlying gene variant in the affected girl and her parents. An FVII activity assay was performed to determine the plasma FVII levels in the girl and her parents. Chorionic villus sampling for fetal DNA acquisition was performed. DNA extraction and polymerase chain reaction (PCR)-sequencing of exon 1 of the F7 gene were performed on fetal DNA samples. An FVII activity assay was performed on the neonate to determine the severity of FVII deficiency. In the next two years, clinical presentations of the two children were collected. Molecular analysis revealed the c.1A>G (p.Met1Val) variant in exon 1 of the affected girl, who was homozygous for this variant in the F7 gene and had severe FVII deficiency (<1%). Both parents were heterozygous for this variant, with FVII levels of 33% and 50% in the mother and father, respectively. PND revealed that both fetuses were homozygous for the c.1A>G variant, leading to termination of the second pregnancy. During the third pregnancy (Second PND), while the mother was being cared for for breast cancer, the homozygous child was born without complications, and the mother underwent mastectomy following delivery. Over the following two years, the child has remained asymptomatic, and the mother has also remained healthy after the mastectomy. Successful PND of severe FVII deficiency was achieved through c.1A>G variant detection, with coordinated multidisciplinary care enabling favorable maternal and fetal outcomes despite concurrent breast cancer treatment.
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with genetic and clinical characteristics. Recent advances in multi-omic technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, immunomics, microbiome profiling, and both spatial and single-cell analyses, have greatly enhanced our understanding of AML pathobiology. Substantial multi-omic studies show that recurrent driver mutations not only impart traditional genomic lesions but also participate in chromatin restructuring, transcriptional and splicing program alterations, host metabolism, and immune evasion mechanisms. Transcriptomic subclassification has improved AML classification beyond cytogenetic and mutational systems, while proteogenomic profiling has elucidated the mechanisms of chemotherapy resistance and provided new druggable targets. The use of metabolomic and immunometabolomic approaches has illuminated nutrient dependencies and metabolic vulnerabilities, while spatial/single-cell multi-omics has revealed unprecedented detail about leukemic heterogeneity and bone marrow niche organization. Multi-omics has also helped establish or refine prognostic models, identify candidate biomarkers, develop patient stratification strategies, and design targeted and immune-based therapies. The multi-omics approach provides a mechanism to rationalize the complex molecular, cellular, and microenvironmental nature of AML and represents a pathway for precision medicine, provided that methodological harmonization, large-scale rigorous validation, and equitable clinical adoption of these approaches can be achieved.
Prostate cancer (PCa) is one of the most common malignancies among men worldwide, and early detection is critical for improving clinical outcomes. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis due to their stability in blood and association with tumor-related molecular alterations. In this study, machine learning (ML) methods were applied to large-scale circulating miRNA expression data to develop a diagnostic model for PCa detection. Serum miRNA expression profiles were obtained from the Gene Expression Omnibus dataset GSE211692, which included 6,920 samples comprising 1,027 PCa cases and 5,893 non-cancer controls. To reduce the risk of overfitting and information leakage, preprocessing, normalization, feature selection, and hyperparameter optimization were performed within the training and cross-validation framework, with the held-out testing set used only for final internal evaluation. Four ML algorithms, namely Logistic Regression, K-Nearest Neighbors, Random Forest, and CatBoost, were implemented. Principal component analysis (PCA) was additionally performed on both the training and held-out test datasets to visualize the sample distribution by case-control status. Although PCA showed clear separation between PCa and non-cancer samples, complete batch-related metadata were unavailable; therefore, potential technical batch effects could not be fully excluded. Among the evaluated algorithms, the Random Forest classifier showed the strongest internal diagnostic performance. A three-miRNA panel comprising miR-1290, miR-1307-3p, and miR-4783-3p demonstrated strong discriminatory capability for PCa classification. However, because the model was developed and evaluated on a single public dataset without external validation, the reported performance should be interpreted with caution. Further validation in independent clinical cohorts, comparison with established biomarkers such as PSA, and integration of clinicopathological variables are required before clinical translation can be considered.
The article reveals the variability of the genome of cattle of the local small-numbered domestic Brown Carpathian breed using cytogenetic and molecular genetic polylocus markers, and justifies the need to integrate local breeds into the modern system of agricultural production in accordance with FAO requirements. The work aimed to study the genetic uniqueness of cows of the brown Carpathian breed using cytogenetic and molecular genetic markers. The karyotype of the animals corresponded to the species norm and was 2n = 60 chromosomes. The level of somatic aneuploidy was 2.5%, and polyploidy and asynchronous divergence of centromeric regions of chromosomes were not detected. Chromosomal breaks were 0.56%. Various types of translocations 5;23 and 11;21, as well as centric fusion according to the Robertsonian type 1;29, were not found. ISSR-studies of dinucleotide ((GA)6CC, (AG)8CG, (AG)8CA, (GA)9C and (AG)9C) and trinucleotide microsatellite loci ((ACC)6G, (CTC)6C, (GAG)6C) 94 amplified DNA fragments were found, of which 31 were polymorphic, which is 32.98%. The total proportion of polymorphic loci was P = 0.218, and the average value of the polymorphism index PIC = 0.142, the average per locus genetic diversity, HS = 0.94, and the Shannon heterogeneity index, I = 0.071. The proportion of conservative loci was K = 7.9. Our findings demonstrated that the Brown Carpathian cattle show chromosomal stability, high genetic consolidation; however, a certain degree of genetic diversity is preserved and incorporated into the previous paragraph.
Skin cancer is a major disease that affects older subjects in the US. There are 56 million Americans 65 years and older in the US and the median age for melanoma diagnosis in the United States is 66 years. Each year 6 M patients are treated for skin cancer including basal cell carcinoma, squamous cell carcinoma, and melanoma. Both melanoma and squamous cell carcinoma can metastasize with melanoma being more likely to metastasize compared to squamous cell carcinoma and lead to death. The need to screen older subjects for skin cancer is critical. In this paper the probability of classifying lesions as either melanoma or squamous cell carcinoma using a convolutional neural network model is reported to be between 92% and 100%. These results are based on OCT gray scale images and AI and can be used as part of a telemedicine session to evaluate skin cancers. Individual areas of cancerous lesions were classified with probabilities of between 90% and 99%. Using this approach, large numbers of patients can be rapidly classified and evaluated, especially in remote areas using mobile healthcare units. In these areas dermatologist visits are difficult to schedule and larger screening efforts are needed.
Changes in the environment driven by climate change are becoming significant stressors that impact brain function, but the connections between these changes and neural plasticity remain unclear. This review aims to offer a comprehensive synthesis of the impact of climate-related stressors on neural plasticity via genetic and epigenetic mechanisms. A structured literature search (2000-2025) was conducted using PubMed, Scopus, and Web of Science, integrating evidence from in vitro, animal, and human studies. Findings indicate that stressors such as heat, pollution, psychosocial adversity, and hypoxia alter neural plasticity through interconnected pathways, such as oxidative stress responses, mitochondrial adaptation, neurotrophic signaling, and epigenetic regulation. The strength of evidence varies; mechanistic insights are primarily obtained from experimental models, whereas human data are mostly associative. We propose a framework for an adaptive-maladaptive continuum based on the intensity, duration, and timing of stressors in development. Overall, this review highlights key knowledge gaps and provides a structured roadmap to improve causal inference and translational relevance.
Osteogenesis Imperfecta (OI) is a rare genetic disorder caused by mutations in genes that encode collagen, with varying clinical presentations. While some studies in Indonesia have reported OI’s clinical features and treatments, there is a lack of comprehensive national data, with limited awareness and access to specialized care for affected individuals. This collaborative study, involving multiple centres across Indonesia, aims to address data fragmentation by analyzing patient characteristics, clinical manifestations, and radiographic features of OI. This multi-centre study included 85 patients diagnosed with OI by expert clinicians across eight centres in Indonesia. Patients with alternative possible diagnoses were excluded. Data were collected through interviews, clinical evaluations, and medical records, focusing on patient characteristics, clinical manifestations, and radiographic features. Of 85 patients (43 males, 42 females), the most common age group was 0-5 years. Low birth weight (<2500 g) was observed in 31.25%, preterm pregnancies in 23.75%, history of miscarriages in 15.6%, advanced maternal age in 12.5%, and family history of OI in 30.9%. Fractures were the most frequent clinical feature (88.75%), followed by blue sclera (84.7%) and dentinogenesis imperfecta (35.4%). Deformities in the lower limbs were most prevalent (83.1%). Radiographic analysis showed bowing of long bones (97%), fractures (93.5%), and osteopenia (82.1%) as the most common manifestations. The study provides an overview of clinical and radiographic characteristics of OI in Indonesia and supports improved awareness to optimize patient outcomes.
Isolated duplications of the long arm of chromosome 3 (3q) are rare chromosomal abnormalities. To date, approximately 32 pure cases have been documented. Most reported 3q duplications arise from unbalanced translocations or inversion-loops mechanisms and are associated with additional chromosomal imbalances, making pure duplications particularly valuable for genotype-phenotype correlations. We report a 17-year-old female with a de novo pure tandem duplication of 3q26.33-q28 (~10.945 Mb). The clinical course was marked by neonatal distress with hypotonia, severe global developmental delay (independent walking at 24 months, language acquisition at 4 years), intellectual disability, autism spectrum disorder, and epilepsy. Dysmorphic features included esotropia, thin upper lip, high arched eyebrows, flat occiput, short neck, and generalized hirsutism. Notably, the patient exhibited increased birth weight (4000 g), contrasting with the growth retardation commonly described in 3q duplication syndrome, and no congenital cardiac anomalies were detected. Conventional R-banded karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA) were performed on peripheral blood samples from the patient and both parents. Karyotype analysis revealed 46, XX, add(3)(q?). CMA identified a duplication defined as arr[GRCh37] 3q26.33q28(179,659,847_190,604,567) × 3. FISH analysis confirmed the tandem configuration of the duplicated segment. Parental karyotypes were normal, supporting a de novo origin of the rearrangement. The duplicated region encompasses 31 OMIM morbid genes, including SOX2, IGF2BP2 and TP63. This case represents the first reported pure 3q duplication since a 2023 comprehensive review, which documented 31 cases. The phenotypic profile suggests region-specific contributions to the 3q duplication syndrome phenotype. This case provides a refined genotype-phenotype correlation and underscores the diagnostic value of an integrated cytogenetic approach combining conventional and molecular techniques.
Sensorineural hearing loss (SNHL) describes a diverse group of clinically and genetically distinct disorders of the auditory system. SNHL is associated with mutations in up to 150 genes. Among them is Cadherin 23 (CDH23), which is associated with both Usher syndrome and non-syndromic hearing loss. In the current study, we used WES to find the genetic cause of SNHL in an extended Iranian family. WES and subsequent Sanger sequencing confirmed the occurrence of a novel homozygote variant in the CDH23 gene (c.817T>C, p.Tyr273His) in affected individuals of this pedigree and its transmission from the parents. This novel variant in the CDH23 was suggested as the cause of the profound SNHL in this family. Further functional research is needed to confirm the results.
Craniosynostosis is a disorder characterized by premature closure of cranial sutures, resulting in restricted skull growth perpendicular to the affected suture and compensatory growth in other directions. Over 180 syndromes have been classified under craniosynostosis, of which eight are associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene: isolated coronal synostosis, Pfeiffer syndrome, Crouzon syndrome, Apert syndrome, Beare–Stevens syndrome, Jackson–Weiss syndrome, Crouzon syndrome with acanthosis nigricans, and Muenke syndrome. Apert syndrome (acrocephalosyndactyly type I) accounts for approximately 4.5% of all craniosynostosis cases, with a prevalence ranging from 1 to 15 per 100,000-160,000 live births. In Ukraine, the prevalence of this syndrome has not been studied. Although the causative gene has been identified, the precise role of FGFR2 mutations in craniofacial dysmorphology and related anomalies remains under investigation. Much of the current understanding of this rare disorder has been facilitated through mouse models. In this report, we present a rare case of prenatally diagnosed Apert syndrome during the second trimester of pregnancy in a young couple with a history of primary infertility and two early pregnancy losses. Postmortem molecular analysis of placental chorionic cells identified a pathogenic FGFR2 mutation (c.755C>G; p.Ser252Trp), enabling precise confirmation of the diagnosis.
Rauvolfia tetraphylla L. (1753) is an important medicinal species of Apocynaceae, widely used for its rich indole alkaloids and related bioactive compounds. We report the first complete chloroplast genome of R. tetraphylla. The genome exhibits a typical circular quadripartite structure of 155,667 bp, with an overall GC content of 37.8%. The genome comprises a large single-copy (LSC) region of 86,332 bp, a small single-copy (SSC) region of 17,853 bp, and a pair of inverted repeat (IR) regions of 25,741 bp each. A total of 130 unique genes are identified, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis strongly supports the close relationships among Rauvolfia species and indicates that R. tetraphylla represents an early-diverging lineage within the genus. Overall, this study enhances our understanding of the chloroplast genome characteristics and evolutionary history of R. tetraphylla and related taxa.
Noonan syndrome (NS) is an autosomal dominant disorder with a wide spectrum of symptoms and clinical phenotypes, including short stature, congenital heart defects (CHD), and distinctive facial features. A pathogenic variant in the PTPN11 gene is the major cause of NS. This is a preliminary study in Indonesia involving 29 patients with clinical features of NS. Detailed clinical and echocardiography data were collected. Genomic DNA was extracted from a peripheral blood sample. Exome sequencing or PCR followed by Sanger DNA sequencing was done. Variant pathogenicity was assessed using the ClinVar database, while the novel variant was analyzed in silico using PolyPhen, Rare Exome Variant Ensemble Learner (REVEL), SIFT, FATHMM Pred, and MutationTaster. Clinical findings in 18 patients showed a typical craniofacial feature of NS, including low-posteriorly rotated ear (83.3%), microcephaly, downslanted palpebral fissures, and a short-webbed neck in 50%, and hypertelorism and a depressed nasal bridge in 44.4%. Other clinical variabilities included CHD (83.3%), thoracic and musculoskeletal deformities (77.8%), short stature (72.2%), and intellectual disability (ID) (50%). A novel variant in exon 3 of PTPN11 was found in one patient: c.140G>A (p.Arg47Lys), which was predicted to be probably damaging. A variant in exon 8, the c.907G>A (p.Asp303Asn), was found in 11 patients. This variant is not in the ClinVar database yet; however, it was reported in a case report and predicted to be probably damaging. One patient has a variant c.184T>G (p.Tyr62Asp), 1 patient has c.854T>C (p.Phe285Ser), 1 patient has c.922A>G (p.Asn308Asp), 2 patients have c.1510A>G (p.Met504Val), and 1 patient has c.1517A>C (p.Gln506Pro), those variants have been previously reported. Sequencing on the remaining exons of PTPN11 is still ongoing. NS patients with PTPN11 variants demonstrate diverse clinical manifestations. Clinicians’ awareness of suspecting NS is essential for early diagnosis, particularly in children with short stature, ID, and CHD who have a distinctive facial dysmorphism at any age.
Tuberous sclerosis (TS) is one of the most common hereditary tumor syndromes, occurring with an average incidence of 1 in 9,000 newborns worldwide. The disease manifests itself through the development of tumors of the brain, kidneys, heart, lungs, and skin, along with characteristic depigmented spots. Tuberous sclerosis is caused by germline variants in the TSC1 (encoding hamartin) and TSC2 (encoding tuberin) genes. The hamartin-tuberin protein complex, together with the TBC1D7 molecule, inhibits the serine/threonine protein kinase mTORC1 (mammalian target of rapamycin complex 1), which is essential for cell proliferation and growth. Accordingly, the use of mTOR inhibitors in the treatment of tuberous sclerosis affects the pathogenesis of the disease and tumor development. Meta-analyses have confirmed the efficacy of mTOR inhibitors in the treatment of tuberous sclerosis, making molecular genetic confirmation of the diagnosis essential for treatment planning. To analyze the clinical and genetic characteristics of tuberous sclerosis in the Republic of Bashkortostan (RB). A retrospective study of patients with tuberous sclerosis registered at the Republican Medical Genetic Center was conducted. 23 programs were used to assess the pathogenicity of newly discovered variants. The odds ratio (OR) was calculated manually using the formula: OR = (A × D)/(B × C). Currently, 88 cases of tuberous sclerosis have been registered in RB, of which 5 patients had pathogenic variants in the TSC1 gene, 19 had pathogenic variants in the TSC2 gene, and 4 people had extensive deletions of the TSC2 gene. Compared with global data, a statistically significantly lower incidence of subependymal nodules, cortical tubers, renal angiomyolipomas, gingival fibromas, pulmonary lymphangiomyomatosis, facial angiofibromas, cognitive impairment, and autism was determined. The significantly lower incidence of brain and internal organ tumors may be due to genetic factors affecting the disease in the region. In 28 of 88 patients with tuberous sclerosis (33%), the diagnosis was confirmed at the genetic level, which forms the basis for treatment with mTOR inhibitors, which is being administered to 8 patients.
Stem cell-derived exosomes (SDEs) have emerged as revolutionary mediators in cancer immunotherapy, offering unprecedented potential to reprogram the immunosuppressive tumor immune microenvironment (TIME). These nano-sized extracellular vesicles, laden with non-coding RNAs (ncRNAs), serve as natural biocompatible carriers, capable of orchestrating immune cell dynamics, stromal remodeling, and tumor cell fate. Unlike their tumor-derived counterparts, which often propagate oncogenic signals, SDEs uniquely harbor immunomodulatory miRNAs (e.g., miR-155, miR-342-3p) and lncRNAs (e.g., MALAT1, XIST) that recalibrate TIME components, activating cytotoxic CD8+ T cells, polarizing macrophages toward anti-tumor M1 phenotypes, and suppressing regulatory T cells (Tregs). This review delineates how SDEs leverage ncRNA cargo to dismantle immunosuppressive barriers: by silencing checkpoint molecules (PD-L1), reversing chemoresistance, and rewiring cancer-associated fibroblasts (CAFs). We highlight the dual roles of exosomal ncRNAs, such as miR-126, which initially bolster cancer stemness but, upon sustained delivery, trigger tumor-selective necroptosis, underscoring their context-dependent therapeutic utility. Despite promising preclinical outcomes, challenges in scalable production, off-target effects, and tumor heterogeneity necessitate engineered solutions, CRISPR-edited exosomes, surface-targeted modifications, and combinatorial regimens with checkpoint inhibitors. By integrating mechanistic insights with translational advances, this review positions SDEs as a paradigm-shifting tool in precision oncology and advocates for multidisciplinary strategies to harness their full potential. As the field evolves, SDE-based therapies stand poised to redefine cancer treatment, transforming the TIME from a fortress of immune evasion into a battleground for tumor eradication.
The editors of OBM Geriatrics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2025. We greatly appreciate the contribution of expert reviewers, which is crucial to the journal's editorial process. We aim to recognize reviewer contributions through several mechanisms, of which the annual publication of reviewer names is one. Reviewers can download a certificate of recognition directly from our submission system. Additionally, reviewers can sign up to the Web of Science Reviewer Recognition Service (formerly Publons) (https://webofscience.com/wos/) to receive recognition. Of course, in these initiatives we are careful not to compromise reviewer confidentiality. Many reviewers see their work as a voluntary and often unseen part of their role as researchers. We are grateful for the time reviewers donate to our journals and the contribution they make.
