Background/ Aim: MicroRNAs (miRNAs) are known up-to-date candidate biomarkers for several diseases. In addition obtaining miRNA from different body fluids such as serum, plasma, saliva, and urine is relatively easy to handle. Herein we aimed to detect miRNAs as biomarkers for early stage prostate cancer (PC). For this purpose, we used urine and serum samples to detect any significant differences in miRNA profiles between patients and healthy controls. Total ribonucleic acid (RNA) in urine and serum samples were isolated from eight untreated PC patients and thirty healthy individuals were screened for miRNA profile and candidate miRNAs were validated. Whole urinary and serum miRNA profile was analyzed using Affymetrix GeneChip miRNA 4.0 Arrays. Candidate miRNAs were investigated by stem-loop reverse transcription - polymerase chain reaction. According to our results, when analyzed urinary samples of PC patients 49 miRNAs were detected up-regulated and 14 miRNAs were found down-regulated when compared with healthy controls. According to the serum samples 19 miRNAs were found up-regulated and 21 miRNAs were found down-regulated when compared with healthy individuals as well. Interestingly we detected overlapped only four miRNAs (MIR320A, MIR4535, MIR4706, MIR6750) that commonly increase or decrease in both serum and urine samples. Among them MIR320A was found down-regulated, and MIR4535, MIR4706, MIR6750 were found up-regulated fo urine samples. However only MIR6750 was up-regulated and the other three miRNAs were down-regulated for serum samples. Notably, the expression profile of MIR320A was significantly altered in urine specimens of prostate cancer patients. We considered that MIR320A has been evaluated as a valuable biomarker that can be used in the early diagnosis of the PC.

Lichens are stable symbiotic associations between fungus and algae and/or cyanobacteria that have different biological activities. Around 60% of anti-cancer drugs are derived from natural resources including plants, fungi, sea creatures, and lichens. This project aims to identify the apoptotic effects and proliferative properties of extracts ofBryoria capillaris (Ach.) Brodo&D.Hawksw,Cladonia fimbriata (L.) Fr.,Evernia divaricata (L.) Ach.,Hypogymnia tubulosa (Schaer.) Hav.,Lobaria pulmonaria (L.) Hoffm., andUsnea florida (L.) Weber ex Wigg. lichen species on prostate cancer cells. Lichen extracts were performed by ethanol, methanol, and acetone separately by using the Soxhlet apparatus and the effects of the extracts on cell viability, proliferation, and apoptosis were measured with the utilization of MTT, LDH assay, Annexin V assay, and Western Blot. Findings of our study revealed a positive correlation between the elevation of cell sensitivity and the increase in the treatment doses of the extract in that higher doses applied reverberate to higher cell sensitivity. A similar correlation was also identified between cell sensitivity elevation and the duration of the treatment. Evidence in our study have shown the existence of an anti-proliferative effect in the extracts ofBryoria capillaris,Evernia divaricata (L.) Ach.,Hypogymnia tubulosa (Schaer.) Hav.,Lobaria pulmonaria (L.) Hoffm., andUsnea florida (L.) Weber ex Wigg., while a similar effect was not observed in the extracts ofCladonia fimbriata.Evernia divaricatainduced anti-proliferative and apoptotic effects in PC-3 cells,whichinduced apoptotic cell death by both extrinsic and intrinsic pathways.Hypogymnia tubulosahas been shown to have anti-proliferative and apoptotic effects in all extractions methods and our findings identified that both the percentage of the apoptotic cells and apoptotic protein expressions recorded an increase at lower treatment concentrations. AlthoughLobaria pulmonariais known to have significant cytotoxic effects, we did not observe a decrease in cell proliferation. Indeed, proliferation marker proliferating cell nuclear antigen (PCNA) protein expression levels have shown an increase in all extracts, whileUsnea florida exhibitedapoptosis induction and slight proliferation reduction in extract treatments with lower concentrations. We tested 18 extracts of six lichen species during our study. Of these,Evernia divaricataandHypogymnia tubulosademonstrated significant apoptotic activity on prostate cancer cells including at low concentrations, which implies that it is worth pursuing the biologically active lead compounds of these extracts on prostate cancerin vitro. Further corroboratory studies are needed to validate the relative potential of these extracts as anti-metastatic and anti-tumorigenic agents.

Permanent hypoparathyroidism is an endocrine disease that is mostly associated with the disruption of the parathyroid glands during surgery. Allotransplantation is the most promising approach for treatment particularly for its cost-effective and exact curative potential. Herein our aim was to evaluate human leukocyte antigen (HLA)-A allele matching effect on clinical improvement and graft survival after parathyroid transplantation. We performed parathyroid transplantation between ABO/Rh compatible recipient and an unrelated donor who has chronic kidney disease. Preoperative immunological tests include panel reactive antibody, T-flow cytometry crossmatch, B-flow cytometry crossmatch, autoflow cytometry crossmatch, and complement-dependent cytotoxicity crossmatch tests were performed. After histopathological evaluation, half of the resected parathyroid gland cells were isolated and transplanted to the omentum surface by laparoscopy. The transplantation outcome was followed up throughout 382 days. The recipient discharged 2 days after transplantation without any complication. During follow-up, calcium and vitamin D supplementation reduced to a one-third dose; even the intact PTH levels remained low. However, clinical improvement was observed by serum calcium levels. The recipient still continues with low-dose supplementation after 382 days of post-transplantation. Parathyroid cell transplantation to the omental tissue is the most promising option even with only one allele matching for patients with using lifelong high-dose supplementation. Clinical improvements and long-term effect of HLA-A allele matching should be evaluated with more studies and in larger cohorts as well.

Theranostic agents hold great promise for personalized medicine by combining diagnostic and therapeutic functions. Herein, two novel multifunctional theranostic glyconanoprobes targeting breast cancer were engineered for synergistic dual chemo-gene therapy and triple chemo-gene-photothermal therapy. Upconversion nanoparticles (UCNPs) were prepared and coated with a Dox-loaded glycopeptide polymer (P-Dox) to form UCNP@P-Dox for improving stability. UCNP@MP-Dox equipped for triple therapy was prepared by combining UCNP@P-Dox with magnetic (Fe₃O₄, M) nanoparticles with photothermal properties. To regulate the expression of the anti-apoptotic Bcl-2 protein, both UCNP@P-Dox and UCNP@MP-Dox were loaded with anti-Bcl-2 siRNA. Impressive photothermal efficiency and good MRI contrast were demonstrated in preliminary evaluations. Moreover, the UCNP@P-Dox/siRNA nanoprobe for dual therapy was shown in preclinical studies to significantly increase anti-tumor efficacy. In vivo experiments in tumor-induced mice showed nanoprobe accumulation in tumors and enhanced antitumor efficacy with combinatorial therapy over Dox and siRNA alone. This study demonstrates the tumor-targeting capability of multifunctional theranostic glyconanoprobes, establishing chemo-gene synergy as a potent therapeutic strategy for breast cancer.