The aim of our study was to assess the sympathetic nervous system’s involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system’s activity predicts increased gastric carcinoma severity.

Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, and the preservation of the blood–brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, and suboptimal pharmacokinetics. Hydrogels offer a promising solution by encapsulating and controlling the gradual release of these phytochemicals directly at the site of injury. Recent advancements in hydrogel formulations, constructed from biopolymers and functionalized using nanotechnological approaches, could significantly improve the solubility, stability, and targeted delivery of phytochemicals. Controlled release profiles from pH-sensitive and environment-responsive hydrogels could ensure that the compounds’ therapeutic effects are optimally timed with individual and critical stages of post-stroke repair. Moreover, hydrogel scaffolds with tailored material properties and biocompatibility can create a favorable microenvironment, reducing secondary inflammation, enhancing tissue regeneration, and potentially improving functional and cognitive outcomes following stroke. This review explores the potential of integrating phytochemicals within hydrogel-based delivery systems specifically designed for post-stroke recovery. The design and synthesis of biocompatible, biodegradable hydrogels functionalized especially with phytochemicals and their applications are also discussed. Lastly, we emphasize the need for additional robust and translatable preclinical studies.

The purpose of this study is to identify and quantify preclinical changes with the help of optical coherence tomography angiography (OCTA) within the retinal microcirculation of young type 1 diabetes (T1D) patients without clinical signs of diabetic retinopathy (DR) and to compare these results with those obtained from healthy age-matched subjects. OCTA is currently used for monitoring diabetic retinopathy; however, there is no current consensus on which OCTA parameter alterations predict the first clinical signs of diabetic retinopathy. The main challenge that young patients with T1D face during the course of the disease is that they can rapidly progress to the development of DR, especially during adolescence. Moreover, they also present an increased risk of rapid progression toward advanced stages of DR and vision loss compared to type 2 diabetes patients, indicating the importance of early diagnosis and intervention. The limitations of the currently used screening procedures that led to the conceptualization of our study are the difficulties in performing fluorescein angiography tests for diagnosing the clinical signs of DR on young patients, namely the invasive procedure of dye injection, the risk of allergic reactions and the long duration of the examination. Moreover, given the long life expectancy of young T1D patients, it is essential to identify the preclinical changes in retinal microvasculature before reaching the first clinical signs quantifiable by FFA. The clinical study enrolled 119 subjects aged between 4 and 30 years old with a mean age of 13 years old, comprising 61 T1D patients with a mean duration of the disease of 4 years and 8 months and 58 healthy age-matched subjects for the control group. OCTA scans were performed using the RevoNX 130 OCTA device (Optopol) to evaluate the following retinal parameters: foveal avascular zone (FAZ) area, perimeter and circularity, overall foveal thickness, and superficial and deep vessel densities. Statistically significant differences between the two groups were identified for the following parameters: the FAZ area in the T1D group (0.42 ± 0.17) was larger than the control group (0.26 ± 0.080), the FAZ circularity (0.41 ± 0.11) was decreased compared to the control group (0.61 ± 0.08) and the FAZ perimeter was larger (3.63 ± 0.97) compared to the control group (2.30 ± 0.50). The overall foveal thickness was decreased in the T1D group (222.98 ± 17.33) compared to the control group (230.64 ± 20.82). The total vessel density of the superficial capillary plexus (SCP) on an investigated area of 6 X 6 mm centered around the fovea was decreased in the T1D group (37.4164 ± 2.14) compared to the control group (38.0241 ± 2.44). Our data suggest that specific imaging biomarkers such as FAZ perimeter, area and circularity, decreased overall foveal thickness and decreased vessel density in the SCP precede the clinical diagnosis of DR in young T1D patients and represent useful parameters in quantifying capillary nonperfusion in T1D patients without clinical signs of DR.

Background: Diabetic retinopathy (DR) is a neurodegenerative disease of the retina. The aim of our study was to analyze latency changes in a full-field electroretinogram (ERG) in patients with type 2 diabetes. Material: This prospective study included 15 diabetic patients without DR, 16 diabetic patients with non-proliferative DR, 14 patients with pre-proliferative DR, 15 patients with proliferative DR, and 14 age-matched controls. All the participants underwent ophthalmologic examination and full-field ERGs. The ERGs were recorded with the Metrovision MonPackOne system. The latencies were analyzed for “a”- and “b”-waves in the dark-adapted (DA) 0.01 ERG, DA 3.0 ERG, DA oscillatory potentials, light-adapted (LA) 3.0 ERG, and 30 Hz flicker ERG. Results: The delayed responses of healthy subjects compared to diabetic patients without DR were the DA oscillatory potentials (25.45 ± 1.04 ms vs. 26.15 ± 0.96 ms, p = 0.027). When comparing diabetic patients without DR and with non-proliferative DR, we did not obtain statistically significant delays. Significant delays in the DA 0.01 “b”-wave (61.91 ± 5.52 ms vs. 66.36 ± 8.12 ms, p = 0.029), DA 3.0 “b”-wave (41.01 ± 2.50 ms vs. 44.16 ± 3.78 ms, p = 0.035), and LA 3.0 “a”-wave (16.21 ± 0.91 ms vs. 16.99 ± 1.16 ms, p = 0.045) were found between non-proliferative DR and pre-proliferative DR. When comparing the groups of patients with pre-proliferative DR and proliferative DR, the LA 3.0 ERG “b”-wave (32. 63 ± 2.53 ms vs. 36.19 ± 3.21 ms, p < 0.0001), LA 30 Hz flicker ERG “a”-wave (19.56 ± 3.59 vs. 21.75 ± 4.74 ms, p= 0.025), and “b”-wave (32.23 ± 4.02 vs. 36.68 ± 3.48 ms, p = 0.017) were delayed. Conclusions: the electrophysiological findings from our study indicate that there is a substantial dysfunction of the neural retina in all stages of DR.

Objectives: In the current study, we investigated the correlations between retinal microvascular parameters using optical coherence tomography angiography (OCTA) and clinical parameters for a group of 69 young patients with type 1 diabetes mellitus (T1DM). Materials and Methods: This retrospective, exploratory study enrolled 69 patients between 5 years old and 30 years old who met the inclusion criteria. All the study participants underwent a comprehensive ophthalmic examination and OCTA scans for the evaluation of the retinal microcirculation. The retinal OCTA parameters were correlated with the following clinical parameters: the patient’s age at the onset of the disease, the duration of T1DM, the BMI at the time of enrollment in the study, the HbA1C values at onset, the mean values of HbA1C over the period of monitoring the disease and the degree of DKA at onset. Results: For the study group, the foveal avascular zone (FAZ) area and perimeter correlated positively with the mean value of HbA1C (Pearson correlation, Sig.2-Tailed Area: 0.044; perimeter: 0.049). The total vessel density in the superficial capillary plexus (SCP) correlated negatively with the duration of T1DM, based on the superior and inferior analyzed areas (Spearman correlation, Sig.2-Tailed SCP in total region: 0.002; SCP in the superior region: 0.024; SCP in the inferior region: 0.050). The foveal thickness also correlated negatively with the levels of diabetic ketoacidosis (DKA) at onset (Spearman correlation, Sig.2-Tailed: 0.034) and the levels of HbA1C at onset (Spearman correlation, Sig.2-Tailed: 0.047). Further on, the study patients were distributed into two groups according to the duration of the disease: group 1 included 32 patients with a duration of T1DM of less than 5 years, and group 2 included 37 patients with a duration of T1DM of more than 5 years. Independent t-tests were used to compare the OCTA retinal parameters for the two subgroups. While the FAZ-related parameters did not show significant statistical differences between the two groups, the vessel densities in both the SCP and DCP were significantly lower in group 2. Conclusions: Our data suggest that specific alterations in OCTA imaging biomarkers correlate with various clinical parameters: the FAZ area and perimeter increase with higher mean values of HbA1C, leading to poor metabolic control. Moreover, the SCP total vessel density decreases as the duration of T1DM increases. Regarding the vessel densities in the SCP and the DCP, they decrease with a duration of the disease of more than 5 years.

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration.