Search Results (492)

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

Background: Oral wound healing is a complex process influenced by extracellular matrix (ECM) remodeling and cellular migration. Hyaluronic acid (HA) and spermidine (SP) have shown regenerative potential, but their combined effects on oral tissues remain unexplored. This study aimed to characterize the effect of a gel composed of a mixture of HA and SP on the epithelial and connective compartments of oral tissue separately, evaluating (i) collagen turnover and cell migration on primary human gingival fibroblasts (HGFs) and (ii) epithelial integrity and cell proliferation on gingival organotypic cultures (OCs). Methods: HGFs were cultured, treated with HA-SP gel (1:0.5 HA-SP ratio) and evaluated for collagen types I and III (COL-I, COL-III), matrix metalloproteinase (MMP-1) protein and tissue inhibitor of MMP-1 (TIMP-1) levels secreted by the cells upon gel treatment, compared to CT. HGFs were also analyzed through a wound healing assay. Gingival samples were obtained to set OCs and were treated with different HA-SP formulations (HA 0.2%; 1:0.5 HA-SP ratio; 1:5 HA-SP ratio) to evaluate the beneficial addition of SP to HA for epithelial tissue. OC samples were formalin-fixed and paraffin-embedded and were stained with hematoxylin and eosin and immunostained for Ki-67 analysis. Results: In HGFs, the gel induced increased COL-III gene expression relative to that of COL-I after 48 h and stimulated cell migration, in turn favoring connective tissue remodeling and repair. In OCs, the gel preserved epithelial integrity up to 48 h, with the best effects observed with the 1:0.5 HA-SP ratio. After 72 h, epithelial detachment was more evident in HA formulations, suggesting that SP contributes to epithelial integrity. Conclusions: The HA-SP gel may support oral tissue healing by modulating ECM remodeling and maintaining epithelial integrity. The gel containing HA and SP at the 1:0.5 ratio may provide a promising solution for enhancing wound healing. Full article

Stem cells cultured in cell aggregates exhibit higher cell survival rates and enhanced anti-inflammatory and angiogenic effects compared to single cells, constructing a stable and economical cell aggregate culture system that can accurately adjust the mass transfer distance of nutrients, which contributes to improving the therapeutic effects of stem cell aggregates. In this study, an alginate hydrogel microsphere culture system (Alg-HM) was prepared using electrostatic spraying technology and refined by optimizing the electrostatic spraying technology parameters, such as the sodium alginate concentration, voltage, electrospray injection speed, and nozzle inner diameter. Furthermore, by setting the Tip-dropped culture system (Tip-D culture system, created by dropping the resuspended hMSC aggregate–hydrogel solution with a tip to form the hydrogel microsphere) and Matrigel culture system (created by dropping the resuspended hMSC aggregates–Matrigel solution with a tip to form the Matrigel culture system) as the control group and Alg-HM as the experimental group, the culture effect of hMSC aggregates in the optimized Alg-HM culture system was tested; CCK-8 detection and Ki-67 immunofluorescence staining showed that the Alg-HM culture system significantly enhanced the cell proliferation activity of hMSC aggregates after 7 and 14 days of culture. The Calcein-AM/PI cell staining results showed that the Alg-HM culture system can significantly reduce the central necrosis of hMSC aggregates. The RNA sequencing results showed that the Alg-HM culture system can significantly activate the signaling pathways related to cell proliferation in hMSCs. This culture system is helpful for the culture of cell aggregates in vitro and efficient transplantation in vivo. Full article

Due to its sarcoma-derived origin and the associated carcinogenic risks, as well as its lack of tissue-specific extracellular matrix biochemical cues, the use of the injectable gel scaffold Matrigel is generally restricted to research applications. Therefore, the development of new fully synthetic injectable gel scaffolds that exhibit performance comparable to Matrigel is a high priority. In this study, we developed a novel fully synthetic injectable gel scaffold by combining a biodegradable PLGA-PEG-PLGA copolymer, clay nanoparticle LAPONITE®, and L-arginine-loaded metal–organic frameworks (NU-1000) at the nano level. An aqueous solution of the developed hybrid scaffold (PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000) exhibited rapid sol–gel transition at body temperature following simple injection and formed a continuous bulk-sized gel, demonstrating good injectability. Long-term sustained slow release of L-arginine from the resultant gels can be achieved because NU-1000 is a suitable reservoir for L-arginine. PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 hybrid gels exhibited good compatibility with and promoted the growth of human skeletal muscle satellite cells. Importantly, in vivo experiments using skeletal muscle injury model mice demonstrated that the tissue regeneration efficiency of PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 gels is higher than that of Matrigel. Specifically, we judged the higher tissue regeneration efficacy of our gels by histological analysis, including MYH3 immunofluorescent staining, H&E staining, and Masson’s trichrome staining. Taken together, these data suggest that novel hybrid hydrogels could serve as injectable hydrogel scaffolds for in vivo tissue engineering and ultimately replace Matrigel. Full article

The crystallization of soluble salts is one of the most significant agents of deterioration affecting porous building materials in historical architecture. This process not only compromises the physical integrity of the materials but also results in considerable aesthetic, structural, and economic consequences. Soluble salts involved in these processes may originate from geogenic sources—including soil leachate, marine aerosols, and the natural weathering of parent rocks—or from anthropogenic factors such as air pollution, wastewater infiltration, and the use of incompatible restoration materials. This study examines the role of capillary rise as a primary mechanism responsible for the vertical migration of saline solutions from the soil profile into historic masonry structures, especially those constructed with calcareous stones. It describes how water retained or sustained within the soil matrix ascends via capillarity, carrying dissolved salts that eventually crystallize within the pore network of the stone. This phenomenon leads to a variety of damage types, ranging from superficial staining and efflorescence to more severe forms such as subflorescence, microfracturing, and progressive mass loss. By adopting a multidisciplinary approach that integrates concepts and methods from soil physics, hydrology, petrophysics, and conservation science, this paper examines the mechanisms that govern saline water movement, salt precipitation patterns, and their cumulative effects on stone durability. It highlights the influence of key variables such as soil texture and structure, matric potential, hydraulic conductivity, climatic conditions, and stone porosity on the severity and progression of deterioration. This paper also addresses regional considerations by focusing on the context of Spain, which holds one of the highest concentrations of World Heritage Sites globally and where many monuments are constructed from vulnerable calcareous materials such as fossiliferous calcarenites and marly limestones. Special attention is given to the types of salts most commonly encountered in Spanish soils—particularly chlorides and sulfates—and their thermodynamic behavior under fluctuating environmental conditions. Ultimately, this study underscores the pressing need for integrated, preventive conservation strategies. These include the implementation of drainage systems, capillary barriers, and the use of compatible materials in restoration, as well as the application of non-destructive diagnostic techniques such as electrical resistivity tomography and hyperspectral imaging. Understanding the interplay between soil moisture dynamics, salt crystallization, and material degradation is essential for safeguarding the cultural and structural value of historic buildings in the face of ongoing environmental challenges and climate variability. Full article

Background/Objectives: Avulsion is a major cause of tooth loss, and its treatment involves replantation. This study analyzed the repair process of incisive teeth subjected to delayed replantation after topical treatment with ampicillin and tetracycline. Methods: Forty male rats were equally divided into four groups: immediate replantation (IM), ampicillin (AM), tetracycline (TR), and dry medium (SE). In the IM group, replantation was performed 5 min after experimental avulsion, whereas in the SE group, the teeth were kept in a dry medium for 60 min. In the AM and TR groups, the teeth were stored in whole bovine milk for 60 min, and then immersed in their respective ampicillin and tetracycline solutions for 5 min. Euthanasia was performed 60 days after the experimental surgery. Histological slides were stained with Hematoxylin and Eosin for quantitative and qualitative analyses. Results: No statistically significant differences were observed among the IM, AM, and TR groups regarding the total resorption area, reattached periodontal ligament fibers, and ankylosis. However, when compared to the SE group, these groups exhibited a smaller total resorption area (IM: p = 0.005; AM: p = 0.0007; TR: p = 0.03), a larger area of periodontal ligament fibers reattachment (IM: p = 0.0002; AM: p = 0.0002; TR: p = 0.02), and a lower presence of ankylosis (IM: p = 0.005; AM: p = 0.0002; TR: p = 0.03). The AM group exhibited the smallest inflammatory resorption. Conclusions: It is concluded that, in an aseptic environment, the use of topical antibiotics such as ampicillin and tetracycline in the treatment of the root surface during replantation of teeth stored in milk is beneficial to the periodontal repair process and root resorption. Notably, ampicillin demonstrated superior efficacy in mitigating inflammatory root resorption and better periodontal ligament reattachment. Full article

Regional anesthesia techniques targeting articular nerve branches offer promising avenues for managing articular pain. This study developed and compared the success rates of an ultrasound-guided versus a blind pericapsular knee desensitization (PKD) technique in canine cadavers. In Phase I, gross dissection and ultrasound evaluations were performed in eight limbs to characterize the anatomy of the medial (MAN), lateral (LAN), and posterior (PAN) articular branches of the saphenous, common fibular, and tibial nerves, respectively, and to identify suitable anatomical and ultrasonographic landmarks. In Phase II, ultrasound-guided and blind PKD injections of a dye solution were randomly performed in 10 cadavers (20 limbs), followed by dissection and histological assessment of staining accuracy. The ultrasound-guided technique achieved a significantly higher overall success rate (96.7%) than the blind technique (73.3%; p = 0.02). The MAN was successfully stained in 100% of ultrasound-guided and 50% of blind injections (p = 0.03), while the LAN and PAN were stained with high but comparable success. Parent nerve involvement was minimal for MAN and PAN but frequent for the common fibular nerve following LAN injections. Histological confirmation supported the anatomical findings, although PAN identification remained inconsistent. These results support the feasibility and increased precision of ultrasound-guided PKD, providing a foundation for further clinical evaluation. Full article

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration (MIBC) of a frozen V lock solution. Methods: Two V-2 mg/mL solutions were tested: (1) V + heparin 100 IU/mL and (2) V + citrate 2%. Solutions were frozen at −20 °C, followed by 48 h refrigeration, and analyses were performed at baseline and after 2, 4, 8, and 12 weeks (experiment 1). In addition, after the 12-week freezing period, solution 1 was also preserved for 1 and 2 weeks at both 4 °C and room temperature (experiment 2). V concentration was assessed by HPLC-DAD at 205 nm and validated with forced degradation tests. A <10% variation indicated significant change. MBIC was determined by XTT staining of 24 h biofilms exposed to decreasing concentrations of each solution. Microorganisms tested included methicillin-susceptible and -resistant Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis ATCC35984 (SE), and a highly biofilm-forming clinical S. epidermidis strain (SEclin). MIBC was defined as ≥50% reduction in metabolic activity. Results: In experiment 1, while V concentration remained stable over time, MIBC values varied, notably increasing from 8 weeks for all strains. Moreover, in experiment 2, significant reductions in both V concentration and MIBC were detected in the 2-week period. Conclusions: V lock solution appears to be able to be 12-weeks frozen followed by up to 1 week at refrigeration or room temperature. This facilitates the optimization of vial preparation in hospital pharmacy laboratories. Full article

Background: Acute phosphate nephropathy (APN) is an underrecognized cause of acute kidney injury (AKI), typically associated with the use of oral sodium phosphate (OSP)-based bowel preparations. It is characterized by calcium phosphate crystal deposition within the renal tubules and may result in permanent renal impairment. Despite known risks, phosphate-containing solutions are still widely used without sufficient risk stratification. Methods: We retrospectively evaluated 517 native kidney biopsies performed in our nephrology clinic between 2017 and 2022. Among these, 12 patients with unexplained AKI and recent colonoscopy history were identified. In nine cases, non-specific tubular deposits on routine staining prompted further histochemical analysis. All had a history of recent OSP-based bowel cleansing. The use of von Kossa staining confirmed calcium phosphate deposition, consistent with APN. Results: Out of 517 kidney biopsies performed during the study period, 9 patients were diagnosed with APN based on histopathological findings following recent colonoscopy and OSP-based bowel cleansing. The mean age was 58.7 years, and three were female. Hypertension was present in seven patients, diabetes mellitus in three, and epilepsy in two; one patient had no comorbidities. Baseline renal function was normal (mean serum creatinine 0.86 mg/dL) and increased to 1.76 mg/dL at three months post-exposure. All biopsies revealed tubulointerstitial calcium phosphate deposits and interstitial inflammation; mesangial hypercellularity was observed in five cases, tubular atrophy in three, and acute tubular necrosis in one. All samples stained positive with von Kossa staining. Over time, all patients developed chronic kidney disease, and one progressed to end-stage renal disease requiring dialysis. Conclusions: In patients presenting with unexplained AKI and recent OSP-based bowel preparation, APN should be considered in the differential diagnosis. When routine histology is inconclusive, definitive diagnosis may require special histochemical staining. Risk-based restrictions on phosphate-containing agents are warranted to reduce preventable kidney injury. Full article

Background/Objectives: Composite dental restorations are continuously exposed to dietary substances, which may compromise their structural integrity. This study aimed to assess the chemical and mechanical effects of coffee, red wine, and Coca-Cola on two widely used commercial resin composites, Herculite Ultra XRV and Omnichroma. Methods: Forty disk-shaped specimens (20 per material) were immersed for 10 days in the selected beverages. Changes in chemical composition were analyzed using Fourier Transform Infrared (FTIR) and Raman spectroscopy, while Vickers microhardness testing evaluated surface hardness. Results: FTIR and Raman analyses revealed that coffee and red wine caused the most substantial chemical degradation, particularly in carbonyl (C=O), aromatic (C=C), and siloxane (Si–O–Si) groups. Herculite XRV demonstrated higher chemical stability, while Omnichroma showed more pronounced molecular degradation. In contrast, microhardness testing indicated that Omnichroma maintained better surface hardness compared to Herculite XRV after exposure. Across all solutions, Coca-Cola induced the least effect. Conclusions: The tested beverages significantly affected both the chemical and mechanical properties of the resin composites. Omnichroma exhibited superior mechanical durability, while Herculite XRV showed greater resistance to chemical degradation. These results highlight the importance of material composition in restorative dentistry and support the development and selection of composites with improved resistance to acidic and staining agents to ensure long-term clinical performance. Full article

Semen quality plays a crucial role in bovine in vivo embryo production. This study aimed to compare the effects of 0 °C-refrigerated semen and liquid nitrogen-frozen semen on embryo quality in Simmental cattle. Semen collected from five bulls was equally divided into two groups: one diluted with a 0 °C refrigeration solution and stored at 0 °C, and the other diluted with a cryopreservation solution and stored in liquid nitrogen for 24 h. We evaluated sperm motility, progressive motility (assessed via a computer-assisted sperm analyzer), acrosome integrity, and plasma membrane integrity in both groups. Fifty superovulated Simmental cows were artificially inseminated with semen from both groups. Embryos were non-surgically flushed on day seven, followed by BrdU proliferation staining and TUNEL apoptosis staining. Proliferation and apoptosis levels were quantified using marker genes. Results showed that 0 °C-refrigerated semen exhibited significantly higher sperm motility, progressive motility, acrosome integrity, and plasma membrane integrity compared to liquid nitrogen-frozen semen (p < 0.05). While total embryo numbers showed no significant difference between groups (p ≥ 0.05), embryos from 0 °C-refrigerated semen contained significantly more proliferative cells (p < 0.05) and fewer apoptotic cells (p < 0.05) than those from frozen semen. These findings demonstrate that 0 °C-refrigerated semen outperforms liquid nitrogen-frozen semen in both sperm quality parameters and resultant embryo quality. Full article

Cryptococcus neoformans (C. neoformans) is a capsulated yeast that enters the body through inhalation and migrates via the bloodstream to the central nervous system, causing cryptococcal meningitis. Diagnosis methods are culture, serology, and India ink staining, which require cerebrospinal fluid (CSF) or whole blood. Molecular methods are used for epidemiological studies and require expensive commercial DNA extraction kits. This study aimed to develop an economical in-house method for extracting C. neoformans DNA from whole blood. C. neoformans cells of varying McFarland standards were spiked into expired blood, then lysed using laboratory-prepared lysis buffer and ox-bile solution, followed by organic DNA extraction. Ordinary PCR targeting the CNAG 04922 gene was performed. To determine the limit of detection, serial dilutions of C. neoformans were made, and DNA extraction was performed on other parts cultured on yeast extract peptone dextrose agar to determine colony-forming units (CFU). The lysis buffer method successfully extracted DNA from as low as the average of 62 CFU in 0.9 mL of expired blood with superior quality and high yield compared to ox-bile. The lysis buffer method yielded higher DNA quality and quantity than ox-bile and detected low concentrations of C. neoformans in expired blood. This method presents a cost-effective alternative for molecular diagnosis in resource-limited settings. Full article

Background: Taste disorders in patients with type 2 diabetes mellitus (T2DM) have a negative impact on their quality of life and glycemic control, and treatment options are limited. Buzhong yiqi formula (BZYQF) improves T2DM symptoms but its effects on T2DM-induced taste disorders have not been sufficiently studied. Methods: Molecular docking was utilized to evaluate binding activity between the compounds in BZYQF and the sweet taste receptors (STRs). T2DM was induced in rats through the administration of high-fat diet and streptozotocin, and the rats were then treated with BZYQF for 8 weeks. Daily indicators and serum biochemical factors were monitored. Taste preferences for sweet, bitter, salty, and sour solutions were assessed using a two-bottle test. The morphology of lingual papillae and the numbers of taste buds were examined using HE staining. A high-glucose (HG) model of taste bud organoids was established to measure sucrose-evoked ATP release. The expression of signaling molecules in the sweet taste receptors (STRs) pathway was determined via RT-qPCR, Western blot, and immunofluorescence in lingual papillae and organoids. Results: A total of 508 compounds in BZYQF indicated good binding activity to T1R2, T1R3 or heterodimers of T1R2/T1R3, and 60 compounds had good binding activity to all three forms of STRs. BZYQF alleviated T2DM symptoms and improved taste perception for maltose (10 mM, 50 mM), quinine (0.03 mM, 0.1 mM), and citric acid (1 mM) solutions. BZYQF improved the morphological structure of lingual papillae and increased taste bud numbers in T2DM rats. BZYQF enhanced ATP release responses to sucrose solution in the taste bud organoids of the HG model. Gene expression determination showed that BZYQF upregulated the expression of signaling molecules in the STRs pathway (T1R2, T1R3, IP3R, α-gustducin, TRPM5) in the lingual papillae of the T2DM rats and in the taste bud organoids of the HG model. Conclusions: BZYQF alleviates T2DM-induced taste disorders by increasing the numbers of taste buds and upregulating STR signaling molecules, in which various compounds, especially flavonoids, exhibit a synergistic effect. Full article

Busulfan (BU) is a widely used chemotherapy drug that has been shown to cause reproductive functional impairment in humans and model animals. However, the precise mechanisms underlying testicular injury induced by BU exposure have not been fully elucidated. Ferroptosis is a form of programmed cell death mediated by iron-dependent lipid peroxidation. The aim of the current study was to determine whether ferroptosis was involved in BU-induced testicular injury. We demonstrated that exposure to BU led to an increase in iron content in the testes of mice. Subsequent western blotting and reverse transcription quantitative PCR, as well as staining of testicular tissue sections, confirmed that ferroptosis mediated BU-induced testicular injury. Consistent with our in vivo findings, we found that ferroptosis, including iron metabolism and the solute carrier family 7 member 11/glutathione peroxidase 4 (xCT/GPX4) signaling pathway, may play a key role in mediating BU-induced injury to GC-1 spg cells in vitro. Treatment with ferroptosis inhibitors slowed cell death caused by BU exposure. Specifically, we found that the administration of zinc protoporphyrin IX (ZnPP), a heme oxygenase 1 (HO1) inhibitor, rescued BU-induced cell death. In conclusion, our in vivo and in vitro findings confirmed that BU exposure led to testicular ferroptosis in mice via the iron intake pathway and the HO1 signaling pathway. Full article

Background/Objectives: In the oral environment, tooth-colored restorations are frequently exposed to staining agents, affecting their aesthetic and physical properties. This study assessed the impact of stains and bleaching agents on the surface roughness, microhardness, and color stability of four different composite materials (Omnichroma, Charisma, Z350, and TPH). Methods: Based on group distribution, the discs of all the composite material samples were prepared. All the ninety-six-disc specimens (n = 96) were then randomly divided into four different groups based on different composite resin groups. The samples were then immersed into four different immersing media [each group had twenty-four-disc samples (n = 24)]. Finally, all the samples then faced the challenge of a bleaching agent application. Measurements were taken at baseline, post-immersion, and post-bleaching stages. Results: Red wine caused increased roughness in Filtek™ Z350 and significant color change in Omnichroma, while coffee increased roughness in Omnichroma and altered the color of TPH spectra. Soda led to increased roughness and significant color change in TPH spectra. Additionally, Filtek™ Z350 experienced reduced microhardness across all solutions after bleaching. Conclusion: This study concluded that staining and bleaching adversely affected the tested composites, with increases in surface roughness, color change, and microhardness reduction observed. Overall, Charisma diamond demonstrated the greatest resilience to staining and bleaching challenges, whereas Filtek™ Z350 XT exhibited the most pronounced degradation, indicating that composite formulation critically governs both aesthetic and mechanical stability under clinically relevant conditions. Full article