Search Results (107)

Objective: This study aimed to investigate the potential splenic tissue damage induced by radiotherapy (RT) and the potential protective effect of different doses of dexmedetomidine on this damage at the histopathological, immunohistochemical, and biochemical levels. Materials and Methods: In our study, Sprague Dawley rats were randomly divided into four groups: Control, Radiotherapy (RT; 8 Gy), RT + Dexmedetomidine 100 µg/kg (RT-D100), and RT + Dexmedetomidine 200 µg/kg (RT-D200). A single dose of 8 Gy radiotherapy was administered to each RT group. Spleen tissues were examined histologically with hematoxylin-eosin and immunohistochemically with anti-Caspase-3, anti-TGF-β1, and anti-TGF-β3 using light microscopy. TBARS and total thiol levels were also analyzed to assess oxidative stress and antioxidant capacity. Results: Histopathological results showed a significant decrease in white pulp diameter, decreased cellular density, and increased congestion in the red pulp in the RT group. Significant fibrosis, sinusoidal dilatation, vacuolization, and amyloid deposition were detected in the white pulp in the RT group. Regarding anti-caspase-3 immunoreactivity, strong positivity increased in the red pulp in the RT group, while a significant increase was observed in the white pulp in both the RT-D100 and RT groups. While the proportion of TGF-β1 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-β3 expression increased significantly only in the RT-D100 group. In biochemical analyses, TBARS levels increased significantly in the RT-D100 group. Total thiol levels decreased in the RT group and increased in the dexmedetomidine-treated groups. Conclusions: While RT caused histopathological damage and increased oxidative stress in spleen tissue, dexmedetomidine reduced this damage in a dose-dependent manner. The different immunohistochemical profiles of TGF-β1 and TGF-β3 suggest that these cytokines may have different functions in the spleen. 100 µg/kg dexmedetomidine stimulates a regenerative response through TGF-β3, while 200 µg/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-β1. Full article

Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and ¹H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC₅₀ values for co-encapsulated formulations, indicating a synergistic effect. Curcumin’s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use. Full article

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients. Full article

Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm²). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms. Full article

Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively. Methods: To evaluate the level of immunoprotection, animals were challenged with L3 of H. contortus two weeks after the last inoculation of the immunogen and humanely sacrificed at 8 weeks post-infection. Parasitological, biopathological, and serological parameters were monitored through the experiment. Parasite burden, abomasal-specific antibody responses, and histopathological changes were determined at the end of the trial. Results: The immunisation protocols resulted in similar reductions in cumulative faecal egg counts (60.5–64.9%) and the total worm burden (47.5–50%) compared to non-immunized (control) animals. Overall, these parasitological data showed an early recovery of the haematocrit (PCV) after challenge in the immunised groups relative to control. Similarly, levels of H. contortus-specific IgG and IgA antibodies increased in both the serum and gastric mucus of immunised groups. Conclusions: These findings represent a further step towards the potential application of this type of immunogen under field conditions, as protective responses (associated with a reduction in faecal egg output) were achieved using a simplified protocol, with lower immunogen doses and fewer inoculations required to induce immunoprotection, thereby mitigating the pathological effects of the parasite and reducing its ability to spread and infect susceptible hosts. Full article

Thiol–epoxy photopolymerization offers exceptional advantages for high-performance protective coatings, yet efficiently curing thick formulations remains a significant challenge due to the limited penetration depth of conventional UV light. Herein, we report a novel near-infrared (NIR) light-activated photopolymerization system for deep-curing applications, strategically integrating upconversion nanoparticles (UCNPs) as NIR-to-UV converters, isopropylthioxanthone (ITX) as a photosensitizer, and a liquid N-phenylglycine-based photobase generator (NPG-TBD) with enhanced resin solubility. Upon 980 nm NIR irradiation, photogenerated TBD efficiently catalyzes thiol–epoxy polymerization through an anionic mechanism, enabling uniform network formation with epoxy and thiol functional group conversions greater than 90% throughout samples exceeding 2.5 cm in thickness. The resulting coatings exhibit excellent mechanical properties including 3H pencil hardness, strong adhesion (0 grade), and good flexibility (2 mm), significantly outperforming conventional UV systems limited to approximately 1.5 mm. Additionally, the cured materials demonstrate multifunctional characteristics including distinctive upconversion luminescence and dual-responsive shape memory behavior. This approach addresses critical limitations in deep-photocuring technology while offering significant potential for applications in protective coatings for marine infrastructure, chemical storage facilities, and smart materials requiring both substantial barrier properties and programmable responsiveness. Full article

The objective was to determine whether dairy cows may activate traditional and alternative inflammatory pathways by consuming a combination of a phytogenic diet (essential oil and pepper resin). Twenty pregnant Jersey cows in the final (third) lactation phase (260 days in milk) were divided into two groups: control, with no additive consumption, and test, with the addition of the phytogenic to the concentrate portion of the diet (150 mg/day/kg dry matter). Blood samples were collected on experimental days 1, 7, 14, 21, 28, 35, and 42 by coccygeal vein puncture to assess the complete blood count, serum biochemistry of levels of total protein, albumin, and globulin, as well as carbohydrate metabolism (glucose), lipid metabolism (cholesterol and triglycerides), protein metabolism (urea), activities of hepatic enzymes (gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST)), cytokine levels (interleukins IL-1β, IL-6, and IL-10), antioxidant response [thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), total thiol (PSH), and non-protein thiol (NPSH), and glutathione S(GST)], cholinergic system [total cholinesterase (ChE) and acetylcholinesterase (AChE)], purinergic signaling [NTPDase, 5′ectonucleotidase and adenosine deaminase (ADA)], and energetic metabolism enzymes [creatine kinase (CK), pyruvate kinase (PK), and adenylate kinase (AK)]. Productive performance was assessed through feed intake and milk production. The results revealed that the use of phytogenic compounds significantly influenced the cholinergic system and purinergic signaling associated with immunology. The reduction in cholinesterase (ChE) activity and the increase in acetylcholinesterase (AChE) activity in lymphocytes suggest the modulation of the cholinergic system, enhancing the immune response. Furthermore, the elevated activity of adenosine deaminase (ADA) in lymphocytes and platelets, together with increased ATP and ADP hydrolysis in platelets, indicates the beneficial regulation of purinergic signaling, potentially contributing to inflammatory modulation. These effects were accompanied by a lower production of pro-inflammatory cytokines (IL-1β and IL-6) and a higher production of IL-10, reinforcing an anti-inflammatory profile. The reduced leukocyte and lymphocyte counts may reflect a lower inflammatory demand, while the increased levels of NPSH and GST antioxidants suggest cellular protection. Despite these physiological changes, productive performance and milk quality remained unaffected. In summary and practical terms, including this additive in the cows’ diet benefits the cow’s health in the final third of gestation when the animal already has a reduced immune response due to advanced gestation. Full article

Acetamidomethyl (Acm)-protected cysteine derivatives are essential components of multi-disulfide synthesis, particularly due to the availability of multimodal removal conditions for Acm protection. Most of these removal conditions are harsh and are commonly used to remove Acm protection at the last step of regioselective synthesis of a multi-disulfide, implying that the removal of Acm is performed in the absence of other Cys thiol protections. In this context, N-chlorosuccinimide (NCS)-mediated removal of Acm and concomitant disulfide bridge formation provides a fast and reliable way to synthesize multi-disulfides. In the present study, we demonstrate that NCS-mediated Acm removal and disulfide bond formation can be performed in the presence of other commonly used Cys thiol protections. Interestingly, Acm can be removed with NCS without affecting the Trt group, which is also removed with I₂. Later, we successfully employ the NCS-based Acm removal method in the synthesis of multi-disulfide peptides like α-conotoxin SI. Full article

Sepsis is a clinical condition causing tissue damage as a result of infection and an exaggerated immune response. Sepsis causes 11 million deaths annually, a third of which are associated with acute lung injury (ALI). Rapid and effective treatment is crucial to improve survival rates. Punica granatum (pomegranate) is rich in polyphenols and demonstrates strong antioxidant activity, while amifostine acts as a free radical scavenger. This study aimed to investigate the antioxidant and anti-inflammatory effects of P. granatum peel extract (PGPE) and amifostine in sepsis-related ALI. Experimental groups included Control, CLP (cecal ligation and puncture-induced sepsis), Amf (200 mg/kg amifostine, intraperitoneally), and PGPE250, and PGPE500 (250 and 500 mg/kg PGPE via oral gavage, respectively). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), tumor necrosis factor-alpha (TNF-α) levels, and metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed in the lung tissue. Biochemical analysis demonstrated that TBARS and TNF-α levels significantly decreased in both the PGPE and amifostine treatment groups compared to the CLP group, while TT levels showed notable improvement. Histopathological evaluation revealed reduced MMP-2 and MMP-9 immunopositivity in the PGPE250 and PGPE500 groups. These findings highlight the lung-protective properties of PGPE, underscoring its potential as a therapeutic agent for sepsis-induced acute lung injury. Full article

Background/Objectives: Acute mesenteric ischemia can lead to severe liver damage due to ischemia–reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Methods: Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Results: Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Conclusions: Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ. Full article

Efficient recovery of gallium (Ga) from vanadium slag processing residue (VSPR) solution is of great significance for environmental protection and resource utilization, but improving its selective adsorption against the coexisting Sc³⁺ and In³⁺ is still challenging. Herein, a novel adsorbent consisting of 4-amino-3-hydrazino-1,2,4-triazol-5-thiol (AHTZT)-modified graphene oxide (GO-AHTZT) was successfully synthesized that exhibits a higher adsorption selectivity for Ga³⁺ in VSPR solution with coexisting Sc³⁺ and In³⁺. Under optimal conditions, the adsorption capacity of GO-AHTZT for Ga³⁺ can reach 23.92 mg g⁻¹, which is 4.9 and 12.6 times higher than that for Sc³⁺ (4.87 mg g⁻¹) and In³⁺ (1.90 mg g⁻¹) adsorption, indicating the excellent anti-interference ability of GO-AHTZT against Sc³⁺ and In³⁺. The process and mechanism of Ga³⁺ adsorption onto GO-AHTZT was also studied and discussed in detail. By measuring the adsorption process and by characterizing the adsorbent before and after adsorption, we demonstrate that the selective interaction between the Ga³⁺- and N-containing groups in AHTZT is the main reason for the improved adsorption selectivity. This work opens up an avenue for the design and synthesis of highly selective adsorbents for Ga³⁺ in complex VSPR solutions. Full article

Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO₂⁻), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO₂⁻, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection. Full article

Quercetin (Q) dietary supplements exhibit poor oral bioavailability because of degradation throughout gastrointestinal digestion (GD), which may be overcome using mesoporous silica particles (MSPs) as an oral delivery system (ODS). This study aimed to elucidate the effect of the functionalization of MSPs with amine-(A-MSP), carboxyl-(C-MSP), or thiol-(T-MSP) groups on their efficiency as a quercetin ODS (QODS). The type and degree of functionalization (DF) were used as factors in an experimental design. The Q-loaded F-MSP (F-MSP/Q) was characterized by gas physisorption analysis, loading capacity (LC), and dynamic light scattering and kinetics of Q release at gastric and intestinal pHs. Antioxidant capacity and Q concentration of media containing F-MSP/Q were evaluated after simulated GD. A-MSP showed the highest LC (19.79 ± 2.42%). C-MSP showed the lowest particle size at pH 1.5 or 7.4 (≈200 nm). T-MSP exhibited the maximum Q release at pH 7.4 (11.43%). High DF of A-MSP increased Q retention, regardless of pH. A-MSP preserved antioxidant capacity of Q-released gastric media (58.95 ± 3.34%). Nonetheless, MSP and F-MSP did not protect antioxidant properties of Q released in intestinal conditions. C-MSP and T-MSP showed essential features for cellular uptake and Q release within cells that need to be assessed. Full article

With the aim to develop novel scaffolds for the sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt)-protected mercapto acids, followed by the removal of the acid labile S-Mmt group. This method allowed for the efficient synthesis of the title compounds in high yield and purity, which were further used in the development of a thioether cross-linked liposome scaffold, by thia–Michael reaction of the terminal thiol groups with pre-formed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by ¹H-NMR, using a Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion NMR experiment (¹H-NMR CPMG), which allowed for real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nano-sized characteristics of the initial liposomes and allowed for the sustained release of calcein (which was used as a hydrophilic dye and a hydrophilic drug model), providing evidence for the efficient synthesis of a novel drug release scaffold consisting of nanoliposome building blocks. Full article

The binding of ubiquitous serum ligands (free fatty acids) to human serum albumin (HSA) or its glycation can affect thiol group reactivity, thus influencing its antioxidant activity. The effects of stearic acid (SA) and glucose binding on HSA structural changes and thiol group content and reactivity were monitored by fluoroscopy and the Ellman method during a 14-day incubation in molar ratios to HSA that mimic pathophysiological conditions. Upon incubation with 5 mM glucose, HSA glycation was the same as HSA without it, in three different HSA:SA molar ratios (HSA:SA-1:1-2-4). The protective effect of SA on the antioxidant property of HSA under different glucose regimes (5-10-20 mM) was significantly affected by molar ratios of HSA:SA. Thiol reactivity was fully restored with 5–20 mM glucose at a 1:1 HSA:SA ratio, while the highest thiol content recovery was in pathological glucose regimes at a 1:1 HSA:SA ratio. The SA affinity for HSA increased significantly (1.5- and 1.3-fold, p < 0.01) with 5 and 10 mM glucose compared to the control. These results deepen the knowledge about the possible regulation of the antioxidant role of HSA in diabetes and other pathophysiological conditions and enable the design of future HSA-drug studies which, in turn, is important for clinicians when designing information-based treatments. Full article