Golestan University of Medical Science

C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9—19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3–84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.

Nanoparticles (NPs) are changing the paradigm of precision oncology by providing means for targeted delivery, immune modulation, and personalized therapies for patients. To this end, drug delivery systems (DDS) have improved the precision in precision medicine and improved the design, delivery, and targeting of immune interventions through the use of NPs. This review aims to address the most clinically relevant NP platforms, including lipid (LNPs), polymeric (PNPs), metal-based (MNPs), ceramic (CNPs), carbon-based (CBNs), aptamer conjugated (ANPs), and quantum dots (QDs), and reviewed as potential therapeutic and diagnostic applications and their utility in oncology. Further, we will touch on next-generation systems, including hybrid NPs (HNPs), stimulus-response NPs (SRNPs), and artificial-intelligence (AI) directed NPs (AI-NPs) that are programmable and adaptive with precision-engineered capabilities for cancer vaccinations and immunotherapy. We will discuss how NPs function as a DDS and how these systems facilitate controlled antigen release, better delivery to antigen-presenting cells, and the delivery of neoantigen-based immunotherapies. The ability of NPs to support cell-based therapies, including CAR-T cells, and help overcome multi-drug resistant (MDR) is also explored. Although obstacles remain regarding the development of scalable, safe, and regulatory approved therapies, the ongoing progress in the field of nanomedicine suggests new strategies enabling the delivery of efficient personalized anticancer therapies with clinical benefits for cancer patients.

By evaluating serum Ribonucleotide-diphosphate Reductase subunit M2 (RRM2) levels and mRNA tissue expression, we aimed to investigate the potential role of RRM2 as a prognostic biomarker in Colorectal Cancer (CRC) patients.

This descriptive-analytic cohort study was conducted on 50 newly diagnosed CRC patients (stage II, III). Real-time PCR determined the mRNA tissue expression of RRM2. Fifty healthy individuals who came to the hospital of Golestan University of Medical Sciences and Tehran University of Medical Sciences for routine check-ups were considered the control group. Serum RRM2 protein was measured using an ELISA method in the patient group before, one month, and three months after the surgery, and in the control group just on the day of a routine check-up. The tumor metastasis node (TMN) classification system and occurrence of liver metastasis were evaluated in CRC patients.

The RRM2 gene expression ratio and 95% confidence interval (CI) of the cancerous tissue was 6.56 times higher than the normal tissue (p < 0.001). Blood Sugar level (BS) (p < 0.001) and platelet level (PLT [range 0.004-499 × 10³ /mm³]; p = 0.010) were higher in the case group compared with the control group significantly, while Mean Corpuscular Volume (MCV) was significantly lower in the case group (p = 0.015). Overall, the mean serum of RRM2 protein levels in patients was remarkably diminished from before surgery until three months after surgery (p < 0.001).

Serum RRM2 level and mRNA expression were significantly higher among CRC patients which could be considered a biomarker regarding CRC progression.