Targeted theranostics: Near-infrared triterpenoic acid-rhodamine conjugates as prerequisites for precise cancer diagnosis and therapy.

Pentacyclic triterpenoic acids have shown excellent potential as starting materials for the synthesis of highly cytotoxic agents with significantly reduced toxicity for non-malignant cells. This study focuses on the development of triterpenoic acid-rhodamine conjugates with fluorescence shifted to the near-infrared (NIR) region for theranostic applications in cancer research. Spectral analysis revealed emission wavelengths around λ = 760 nm, enabling stronger signals and deeper tissue penetration. The conjugates were evaluated using SRB assays on tumor cell lines and non-malignant fibroblasts, demonstrating low nanomolar activity and high selectivity, similarly to their known rhodamine B counterparts. Additional staining experiments proved their mode of action as mitocans.

Digital Holographic Microscopy for Label-Free Detection of Leukocyte Alternations Associated with Perioperative Inflammation after Cardiac Surgery.

In a prospective observational pilot study on patients undergoing elective cardiac surgery with cardiopulmonary bypass, we evaluated label-free quantitative phase imaging (QPI) with digital holographic microscopy (DHM) to describe perioperative inflammation by changes in biophysical cell properties of lymphocytes and monocytes. Blood samples from 25 patients were investigated prior to cardiac surgery and postoperatively at day 1, 3 and 6. Biophysical and morphological cell parameters accessible with DHM, such as cell volume, refractive index, dry mass, and cell shape related form factor, were acquired and compared to common flow cytometric blood cell markers of inflammation and selected routine laboratory parameters. In all examined patients, cardiac surgery induced an acute inflammatory response as indicated by changes in routine laboratory parameters and flow cytometric cell markers. DHM results were associated with routine laboratory and flow cytometric data and correlated with complications in the postoperative course. In a subgroup analysis, patients were classified according to the inflammation related C-reactive protein (CRP) level, treatment with epinephrine and the occurrence of postoperative complications. Patients with regular courses, without epinephrine treatment and with low CRP values showed a postoperative lymphocyte volume increase. In contrast, the group of patients with increased CRP levels indicated an even further enlarged lymphocyte volume, while for the groups of epinephrine treated patients and patients with complicative courses, no postoperative lymphocyte volume changes were detected. In summary, the study demonstrates the capability of DHM to describe biophysical cell parameters of perioperative lymphocytes and monocytes changes in cardiac surgery patients. The pattern of correlations between biophysical DHM data and laboratory parameters, flow cytometric cell markers, and the postoperative course exemplify DHM as a promising diagnostic tool for a characterization of inflammatory processes and course of disease.

Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up -- the SOLO study.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implants in eyes with cystoid macular oedema (CME) secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in the clinical everyday practice, examine the effects of early retreatment and compare the results with the GENEVA study. METHODS: The charts of 102 patients (102 eyes) with CME secondary to BRVO (n = 54) or CRVO (n = 48) treated with Ozurdex at 8 centres were retrospectively reviewed. The patients were examined monthly over a 24-week period. Slit-lamp biomicroscopy, measurement of best-corrected visual acuity (BCVA) and measurement of the central retinal thickness (CRT) with spectral-domain optical coherence tomography (SD-OCT) were performed at baseline and at every follow-up examination. With progression of the disease (loss of one line or increased central retinal thickness (CRT) of 150 µm), a reinjection of Ozurdex or anti-VEGF was offered. Additional supplementing sectorial or panretinal laser photocoagulation was considered based on the individual status of the retina. RESULTS: In the BRVO group, the median BCVA was 0.6 logMAR (Snellen equivalent of 0.25) at baseline and improved to 0.4 logMAR (Snellen equivalent of 0.40) after 4 weeks, 0.3 logMAR (Snellen equivalent of 0.50) after 8 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 12 weeks, 0.5 logMAR (Snellen equivalent of 0.32) after 16 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 20 weeks and 0.45 logMAR (Snellen equivalent of 0.35) after 24 weeks. The mean CRT was 559 ± (SD) 209 µm at baseline and it decreased to 335 ± 148 µm after 4 weeks, 316 ± 137 µm after 8 weeks, 369 ± 126 µm after 12 weeks, 407 ± 161 µm after 16 weeks, 399 ± 191 µm after 20 weeks and 419 ± 196 µm after 24 weeks. In the CRVO group, the median BCVA was 0.7 logMAR (Snellen equivalent of 0.20) at baseline and improved to 0.4 logMAR (Snellen equivalent of 0.40) after 4 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 8 weeks, 0.6 logMAR (Snellen equivalent of 0.25) after 12 weeks, 0.6 logMAR (Snellen equivalent of 0.25) after 16 weeks, 0.5 logMAR (Snellen equivalent of 0.32) after 20 weeks and 0.52 logMAR (Snellen equivalent of 0.30) after 24 weeks. The mean CRT at baseline was 740 ± 351 µm and it decreased to 419 ± 315 µm after 4 weeks, 352 ± 261 µm after 8 weeks, 455 ± 251 µm after 12 weeks, 497 ± 280 µm after 16 weeks, 468 ± 301 µm after 20 weeks and 395 ± 234 µm after 24 weeks. The BCVA improvement was statistically significantly better (p < 0.05) compared with baseline in both groups at every follow-up visit. The mean CRT maintained significantly better when compared with baseline in both groups at all follow-up visits. Early reinjection was indicated in BRVO in 40.7% after 17.5 ± 4.2 weeks and in CRVO in 50% after 17.68 ± 4.2. Six eyes (11%) with BRVO received a sectorial laser photocoagulation at a mean interval of 22 ± 5.0 weeks. Seven eyes (15%) with CRVO received a panretinal laser photocoagulation after a mean interval of 18 ± 7.0 weeks. The BCVA improvement and the mean CRT reduction were statistically significant (p < 0.05) compared with baseline in both groups at every follow-up visit. CONCLUSIONS: Dexamethasone intravitreal implant resulted in a significant improvement of the BCVA and reduction of CME in patients with BRVO or CRVO. Early retreatment after 16 weeks instead of 24 weeks, like in the GENEVA study, was indicated in 50% to stabilize the improved functional and anatomical results.

Delayed inhibition of angiotensin II receptor type 1 reduces secondary brain damage and improves functional recovery after experimental brain trauma*.

OBJECTIVE: To investigate the regulation of the cerebral renin-angiotensin system and the effect of angiotensin II receptor type 1 inhibition on secondary brain damage, cerebral inflammation, and neurologic outcome after head trauma. DESIGN: The expression of renin-angiotensin system components was determined at 15 mins, 3 hrs, 6 hrs, 12 hrs, and 24 hrs after controlled cortical impact in mice. Angiotensin II receptor type 1 was inhibited using candesartan (0.1, 0.5, 1 mg/kg) after trauma to determine its effect on secondary brain damage, brain edema formation, and inflammation. The window of opportunity was tested by delaying angiotensin II receptor type 1 inhibition for 30 mins, 1 hr, 2 hrs, and 4 hrs. The long-term effect was tested by single and daily repeated treatment with candesartan for 5 days after controlled cortical impact. SETTING: University research laboratory. SUBJECTS: Male C57Bl/6N mice. INTERVENTIONS: Brain trauma by use of a controlled cortical impact device. MEASUREMENTS AND MAIN RESULTS: Expression of angiotensin II receptor type 1A decreased by 42% within 24 hrs after controlled cortical impact, whereas angiotensin II receptor type 1B expression increased to 220% between 6 and 12 hrs. Blockage of angiotensin II receptor type 1 with 0.1 mg/kg candesartan within 4 hrs of injury significantly reduced secondary brain damage (30 mins: 25 mm vs. vehicle: 41 mm) and improved neurologic function after 24 hrs but failed to reduce brain edema formation. Daily treatment with candesartan afforded sustained reduction of brain damage and improved neurologic function 5 days after traumatic brain injury compared with single and vehicle treatment. Inhibition of angiotensin II receptor type 1 significantly attenuated posttraumatic inflammation (interleukin-6: -56%; interleukin-1ß: -42%; inducible nitric oxide synthase: -36%; tumor necrosis factor-α: -35%) and microglia activation (vehicle: 163 ± 25/mm vs. candesartan: 118 ± 13/mm). Higher dosages (0.5 and 1 mg/kg) resulted in prolonged reduction in blood pressure and failed to reduce brain lesion. CONCLUSIONS: The results indicate that angiotensin II receptor type 1 plays a key role in the development of secondary brain damage after brain trauma. Inhibition of angiotensin II receptor type 1 with a delay of up to 4 hrs after traumatic brain injury effectively reduces lesion volume. This reduction makes angiotensin II receptor type 1 a promising therapeutic target for reducing cerebral inflammation and limiting secondary brain damage.