Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic stability, resistance in biological environment, and target affinity. To evaluate the effects of nucleobase and/or sugar moiety chemical modifications, five TBA analogues have been designed and synthesized considering that the chair-like G4 structure is crucial for biological activity. Their structural and biological properties have been investigated by Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), native polyacrylamide gel electrophoresis (PAGE) techniques, and PT and MTT assays. The analogue TBAB contains 8-bromo-2′-deoxyguanosine (B) in G-syn glycosidic positions, while TBAL and TBAM contain locked nucleic acid guanosine (L) or 2′-O-methylguanosine (M) in G-anti positions, respectively. Instead, both the two types of modifications have been introduced in TBABL and TBABM with the aim of obtaining synergistic effects. In fact, both derivatives include B in syn positions, exhibiting in turn L and M in the anti ones. The most appealing results have been obtained for TBABM, which revealed an interesting cytotoxic activity against breast and prostate cancer cell lines, while in the case of TBAB, extraordinary thermal stability (Tm approximately 30 °C higher than that of TBA) and an anticoagulant activity higher than original aptamer were observed, as expected. These data indicate TBAB as the best TBA anticoagulant analogue here investigated and TBABM as a promising antiproliferative derivative.

• Book : 26(1)
• Pub. Date : 2025
• Page : pp.134
• Keyword :

Neuroradiology, as a modern branch of the neurosciences and radiological sciences, has an impact on global health, particularly on brain health. On the one hand, neuroradiology directly impacts diseases of the nervous system, such as stroke and inflammatory diseases, by providing an all-in-one package combining imaging, diagnosis, treatment, and follow-up. This has been impacted by the continuous evolution over the last decades of both diagnostic and interventional tools in parallel: this was the case in stroke, where the endovascular treatment was followed closely by developments in fast MRI techniques and multi-slice CT imaging. Additionally, inflammatory diseases of the brain, as well as tumors of the central nervous system, can be imaged and localized in order to set in place both an early diagnosis and initiate treatment. Neurodegenerative diseases such as Alzheimer’s disease, in which treatment options are appearing on the horizon, also benefit from the use of modern neuroimaging techniques. On the other hand, neuroradiology plays an important role in the prevention and prediction of brain diseases and helps in building up the so-called digital twin, often from birth till late in life. Additionally, the practice of neuroradiology itself is evolving to not only improve patient health but also the health of the practitioners of neuroradiology themselves. By improving the overall work environment also, neuroradiologists will be working under better conditions and will suffer less fatigue and burn-out, thereby providing better service to patients and population. By using less radiation for diagnostic tests and shifting to techniques that rely more and more on either magnetic resonance or ultra-sound techniques, the radiation load on the population and on the neuroradiologists will decrease. Furthermore, using less contrast, such as gadolinium, has been shown to result in fewer deposits in the brains of patients, as well as less pollution at the ocean level, thus contributing to general well-being. Additionally, the implementation and use of artificial intelligence at many levels of the diagnostic and treatment chain will be beneficial to patients and physicians. In this paper, we discuss the place and potential not just of the techniques but of neuroradiology and the neuroradiologist as promoters of brain health and thus global health.

• Book : 9(1)
• Pub. Date : 2025
• Page : pp.1
• Keyword :

Abstract

A 9.5‐year‐old male neutered domestic short‐haired cat received two courses of postoperative, definitive‐intent conformal radiation therapy (RT) for recurrent laryngeal adenocarcinoma (LACA). Adjuvant RT was prescribed (16 × 3.0 Gy, total 48 Gy) following incomplete resection. Following tumor recurrence and subsequent incomplete resection 31.5 months after the first course, a second course was prescribed (20 × 2.5 Gy, total 50 Gy). Acute and late adverse events were mild. No evidence of local recurrence was documented 42 months following the second course when the cat was euthanized for renal disease. This first report of long‐term control in a cat with LACA supports further evaluation of surgery and definitive‐intent RT.

• Book : 66(1)
• Pub. Date : 2025
• Page : pp.e13466
• Keyword :

• Book : 923()
• Pub. Date : 2025
• Page : pp.147674
• Keyword :

• Book : 34()
• Pub. Date : 2025
• Page : pp.2253-2259
• Keyword :

Background/Objectives: Periodontitis is an inflammatory disease induced by bacteria in dental plaque that can activate the host’s immune-inflammatory response and invade the bloodstream. We hypothesized that a higher periodontal inflamed surface area (PISA) is associated with higher levels of inflammatory biomarkers, lower levels of antioxidants, and mitochondrial DNA copy number (mtDNAcn). Methods: Using periodontal parameters, we calculated the PISA score, measured the levels of inflammatory biomarkers and antioxidants in the serum, and took buccal swabs for mtDNA and nuclear DNA (nDNA) extraction. Results: Higher PISA was associated with higher CRP levels, higher leukocyte, neutrophil, and erythrocyte counts, and lower magnesium-to-calcium ratio, but not with mtDNAcn. A higher number of deep pockets was associated with higher leukocytes and neutrophil counts and higher uric acid levels. Conclusions: The PISA score might be an appropriate parameter to assess the inflammatory burden of periodontitis, but not to assess mitochondrial dysfunction after mtDNA isolation from buccal swabs.

• Book : 14(1)
• Pub. Date : 2025
• Page : pp.24
• Keyword :

Rosa hybrida is one the most commonly cultivated ornamental plant of economic importance and faces major challenges under heat stress. Melatonin has been widely shown to regulate plant stress response; however, the exact mechanism involved in heat stress in R. hybrida has yet to be determined. Here, we observed that R. hybrida in vitro plantlets supplemented with melatonin in the culture medium exhibited higher chlorophyll content, relative ion leakage, and fresh weight after 12 d of high-temperature treatment; the optimal concentration was established at 5 mg/L. Using molecular and biochemical techniques, we explored the roles of a melatonin synthase gene RhCOMT1, which expression was influenced by heat stress and melatonin. RhCOMT1 was located in the nuclear-cytoplasmic under ambient conditions, while heat stress translocated the distribution of RhCOMT1 to chloroplasts. Overexpression of RhCOMT1 in rose petal enhanced thermotolerance, and silencing of RhCOMT1 reduced thermotolerance via affect H2O2 content and relative ion leakage. These findings collectively emphasize the pivotal role of melatonin in enhancing thermotolerance to R. hybrida by alleviation of oxidative stress, through modulation of RhCOMT1 expression and location.

• Book : 14(1)
• Pub. Date : 2025
• Page : pp.29
• Keyword :

Background/Objectives: Lutathera® ([177Lu]Lu-DOTA-TATE) is the first radiolabelled somatostatin (SST) analog approved for the treatment of patients with well-differentiated (G1 and G2) unresectable or metastatic gastro-entero-pancreatic neuro-endocrine-neoplasms (GEP-NENs). The bone marrow and kidneys are critical organs for RLT with [177Lu]Lu-DOTA-TATE. Our purpose was to evaluate hematological and renal toxicity in 29 patients (18 males, 11 females) treated with Lutathera®. Methods: According to standard protocols, four cycles of (177Lu)Lu-DOTA-TATE were administered every eight/nine weeks. Patients received pre-medication with anti-emetic and anti-acid drugs and a slow amino acid infusion for renal protection. Blood count and serum creatinine data were collected at three time points: before the first cycle, after the second cycle, and at the end of treatment. Results: We found that almost all hematological parameters significantly decreased between the baseline and/or interim and post-therapy evaluation, although without a clinical impact. The presence of total tumor load or bone metastases had no influence on these findings, while male patients showed less hematological toxicity than females. Conversely, creatinine levels did not vary during treatment. Conclusions: Our study confirms that [177Lu]Lu-DOTATATE RLT is safe and well tolerated despite some minor (grade 1) hematological toxicity.

• Book : 6(1)
• Pub. Date : 2025
• Page : pp.1
• Keyword :

Abstract

Can a naked singularity (NkS) be distinguished from a black hole (BH)? We have investigated it with cutting-edge general relativistic magnetohydrodynamic simulations, followed by general relativistic radiation transfer calculation for magnetized accretion flow around NkS and BHs. Based on our simulations, the accreting matter close enough to the singularity repels due to effective potential. This prevents matter from reaching an NkS and forms a quasi-spherical symmetric density distribution around it, unlike the accretion flows around a BH. We observe 1 order of magnitude higher mass flux through the jet and much stronger wind from an NkS than a BH. We found that the jet launching mechanism in an NkS differs significantly from that in a BH. In the horizon-scale images, an NkS shows a photon arc instead of a photon ring that is shown around a BH. In summary, the flow dynamics and radiative properties around an NkS are distinctly different from a BH. These properties would be useful to either confirm or rule out such exotic compact objects through future observations.

• Book : 978(1)
• Pub. Date : 2025
• Page : pp.44
• Keyword :

• Book : 74(1)
• Pub. Date : 2025
• Page : pp.38
• Keyword :