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The purpose of this study was to analyze the ultrastructure of the testes of sexually immature calves and reproductive bulls of the Polish Holstein-Friesian Black-and-White breed. Utilizing TEM, this study identified three distinct stages of seminiferous tubule development in calves, characterized by varying shapes, distributions, and arrangements of individual cells. In immature animals, early developing spermatocytes, prespermatogonia, and pre-Sertoli cells were observed within the seminiferous tubules. In sexually mature bulls, all cells of the spermatogenic series were observed, situated on a thin, multilayered basal lamina, which forms characteristic undulations. An abundant smooth endoplasmic reticulum was observed in the cytoplasm of spermatogonia in both groups of animals, forming characteristic membranous swirls. In adult bulls, spermatogonia maintain contact with each other through numerous cytoplasmic bridges and cell connections, forming small spaces with visible microvilli between them. The ultrastructural analysis facilitated the identification of morphological changes occurring during the maturation of pre-Sertoli cells, transitioning from a large euchromatic nucleus to a nucleus in which the formation of characteristic vesicles and tubules could be observed. It should also be emphasized that two types of Sertoli cells, namely dark and light electron-dense cells, can be found in cattle. These cells differ from each other, indicating that they may perform different functions. The widespread recognition of the presence of two types of Sertoli cells in cattle will undoubtedly contribute to a better understanding of the processes occurring within the testes and provide a basis for further research in this area.

This study focuses on addressing the challenges associated with doxorubicin (DOX), an anthracycline chemotherapeutic widely used in cancer treatment. Despite its efficacy, DOX is linked to severe side effects that limit its clinical applications. Novel pharmaceutical formulations aim to mitigate these issues, providing better safety profiles. The development of these formulations requires analytical methods that can accurately and quickly quantify DOX. A cost-effective and portable electrochemical sensor for DOX detection was developed utilizing in-house printed carbon electrodes decorated with gold nanoparticles. DOX was detected using differential pulse voltammetry. The sensor demonstrated an accurate quantification of DOX from novel pharmaceutical formulations and serum, presenting a dynamic range of 1 to 500 μg/mL and a low detection limit of 0.3 μg/mL. The method, successfully applied to characterize DOX-loaded nanosomes, offers a valuable alternative in the early stages of formulation development, reducing costs and saving time, while maintaining accuracy.

In Tunisia, self-medication is a common practice, and there is a continual rise in the prevalence of cardiovascular disease. Given the lack of data on the self-medication practices (SMPs) among cardiovascular patients in this area, the present study aimed to identify the prevalence and determinants of SMPs among cardiovascular patients in the city of Béja. A community-pharmacy-based survey was conducted among selected cardiovascular patients in Béja, Tunisia, from May 2021 to June 2021. Data were collected using a self-administered questionnaire provided by pharmacists during in-person surveys with patients. Descriptive statistics were used to summarize the data, while Fisher’s exact test was used for categorical variables, with the significance level set at p < 0.05. The frequency of self-medication among the 150 respondents was 96%; 70.14% of participants reported that the primary reason why people engage in self-medication is the existence of an old prescription. The most prevalent conditions leading patients to self-medicate were headaches (100%), fever (83.33%), toothache (65.97%), and dry cough (47.92%). The most frequently self-administered drugs were paracetamol (100%), antibiotics (56.94%), and antitussives (47.92%). The results of our study indicate that SMPs among Tunisian cardiovascular patients have a high prevalence. With this in mind, healthcare practitioners should ask their patients about their self-medication practices and advise cardiovascular patients about the risks and benefits associated with this practice.

Flexible substrates have known increased popularity over rigid ones due to their use in surface-enhanced Raman scattering (SERS). They provide irregular surfaces, ideal for in situ sensing. In this context, we report the SERS performance of hybrid ZnO@Ag thin films deposited by magnetron sputtering (MS) on flexible, thermoplastic substrates. This physical deposition method is acknowledged for obtaining high-quality and reproducible ZnO films that can be embedded in (bio)sensing devices with various applications. Three types of thermoplastic-based, commercially available substrates with different glass transition temperatures (Tg) were chosen for the variation in flexibility, transparency, and thickness. Zeonor® (Tg = 136 °C, thickness of 188 μm) and two types of Topas (Topas®: Tg = 142 °C, thickness of 176 μm; Topas2: Tg = 78 °C, thickness of 140 μm) thermoplastic sheets are nonpolar and amorphous cyclo-olefin polymer (COP) and cyclo-olefin copolymers (COC), respectively. Their thicknesses and different values of Tg can greatly affect the topographical and roughness properties of films with small thicknesses and, thus, can greatly influence the enhancement of the Raman signal. The ZnO films deposited on top of Zeonor® or Topas® have identical morphological properties, as shown by the scanning electron microscopy (SEM) characterization. Subsequently, by using the MS technique, we tuned the thickness of the deposited silver (Ag) films in the range of 7–30 nm to assess the growth influence on the morphology and the SERS signal amplification of the substrates with and without the ZnO intermediate layer. The SEM analysis showed that the Ag atoms migrated both into the interstitial areas, filling the voids between the ZnO granular structures, and over the latter, forming, in this case, isolated Ag clusters. SERS analysis performed on the ZnO-Ag hybrid films using crystal violet (CV) molecule revealed a limit of detection (LOD) of 10−7 M in the case of 15 nm thick Ag/Zeonor® interlayer films ZnO and relative standard deviation (RSD) below 10%.

Pharmacological responses vary by sex in several illnesses. This narrative review summarizes sex variations in pharmaceutical response in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Infection with SARS-CoV-2 is more severe and deadly in men than women. This may be attributed to immunological responses, genetics, and hormones. Some research shows that men may respond better to genomic vaccinations and females to antiviral medications such as remdesivir (Moderna and Pfizer-BioNTech). In dyslipidemia, women tend to have greater HDL-C and lower LDL-C than men. Some studies show that females may need lower statin dosages than men to obtain equal LDL-C reductions. Ezetimibe co-administered with a statin significantly improved lipid profile indicators in men compared to women. Statins reduce dementia risk. Atorvastatin decreased dementia risk in males (adjusted HR 0.92, 95% CI 0.88–0.97), whereas lovastatin lowered dementia risk in women (HR 0.74, 95% CI 0.58–0.95). In diabetes mellitus, evidence suggests that females may have a higher risk of developing certain complications such as diabetic retinopathy and neuropathy, despite having lower rates of cardiovascular disease than males. This could be the result of differences in hormonal influences and genetic factors. Some research shows females may respond better to oral hypoglycemic medications such as metformin. In conclusion, sex-related differences in pharmacological response have been observed in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Further research is needed to better understand these differences and to develop personalized treatment strategies for males and females with these conditions.

Bacterial infections are a major concern as antibiotic resistance poses a great threat, therefore leading to a race against time into finding new drugs or improving the existing resources. Nanomaterials with high surface area and bactericidal properties are the most promising ones that help combating microbial infections. In our case, graphene decorated with silver nanoparticles Gr-Ag (5 wt% Ag) exhibited inhibitory capacity against S. aureus and E. coli. The newly formed hybrid material was next incubated with high-efficiency particulate air (HEPA) filter, to obtain one with bactericidal properties. The modified filter had greater inhibitory action against the tested strains, compared to the control, and the effect was better against the Gram-negative model. Even if the bacteria remained attached to the filters, their colony forming unit capacity was affected by the Gr-Ag (5 wt% Ag) hybrid material, when they were subsequently re-cultured on fresh agar media. Therefore, the HEPA filter modified with Gr-Ag (5 wt% Ag) has high antibacterial properties that may substantially improve the existing technology.

A biogenic carrier for 5-fluorouracil (5-FU) loading and subsequent tableting as a new drug formulation for slow release has been proposed using the biomineral from blue crab carapace. Due to its highly ordered 3D porous nanoarchitecture, the biogenic carbonate carrier could achieve increased effectiveness in colorectal cancer cure provided that the formulation would successfully pass through the gastric acid conditions. Following the recently proven viability of the concept by demonstrating the slow release of the drug from the carrier using the highly sensitive SERS technique, here we investigated the 5-FU release from the composite tablet drug in pH conditions replicating the gastric environment. The released drug from the tablet was studied in solutions with three relevant pH values, pH 2, pH 3, and pH 4. The 5-FU SERS spectral signature for each pH value was used to build calibration curves for quantitative SERS analysis. The results suggested a similarly slow-releasing pattern in acid pH environments to that in neutral conditions. Although biogenic calcite dissolution was expected in acid conditions, the X-ray diffraction and Raman spectroscopy showed preservation of calcite mineral along with the monohydrocalcite during acid solution exposure for two hours. The total released amount in a time course of seven hours, however, was lower in acidic pH solutions, with a maximum fraction of ~40% of the total amount of loaded drug, for pH 2, as opposed to ~80% for neutral values. Nonetheless, these results clearly prove that the novel composite drug retains its slow-releasing character in environmental conditions compatible with the gastrointestinal pH and that it is a viable and biocompatible alternative for oral delivery of anticancer drug to reach the lower gastro-intestinal tract.

Alkylating agents such as cyclophosphamide (CPA) are commonly used in cytotoxic or immunosuppressive therapies for different types of diseases. One of the main secondary effects of such therapy is the reduction in follicular reserve, targeting the primordial follicles. The aim of this study was to investigate the antioxidant and protective effects of Plantago sempervirens extract on the follicular pool. The experiment was performed on Wistar female rats, for 21 days. They were divided into five groups according to the treatment they received (Control, CPA (200 mg/kg BW), P. sempervirens extract in three different doses—25/50/100 dw/mL ethanol extract (5 mL/kg BW)). The investigations regarded enzymatic and non-enzymatic nitro-oxidative stress, hormone levels (FSH and estrogen), TEM sections of the ovaries, and oestrus cycle monitorization. CPA strongly increased the oxidative stress (TOS—32.8 mmol H2O2/L; NO—68.60 μmol/L; OSI—6.82), alongside a depletion of FSH and a blockage of the oestrus cycle in the metestrus phase. The follicular pool was strongly depleted during CPA exposure, but FSH concentration and the TEM images of the cells revealed a significant improvement after treatment, as the dose increases (P3). Therefore, these findings reveal that P. sempervirens therapy could have a potential protective effect against CPA-induced acute damages in the ovaries, as well as maintaining a functional oestrus cycle.

Three ceramic and composite computer-aided design/computer-aided manufacturing (CAD/CAM) materials from different manufacturers (Cerasmart (CS)—nanoceramic resin; Straumann Nice (SN)—glass ceramic and Tetric CAD (TC)—composite resin) were tested to investigate the biocompatibility and sustainability on human fibroblasts and keratinocytes cells. Each type of CAD/CAM blocks restorative materials with fine and rough surfaces was exposed to an acidic environment for one month. After that, various powders were obtained by milling. In parallel, powders were also prepared from each restorative material, which were not exposed to the acidic environment. The cytotoxic effects were investigated by means of MTT and LDH assays, as well as nitric oxide production on two human normal cell lines, namely, fibroblasts (BJ) and keratinocytes (HaCaT). In addition, the degree of adhesion of fibroblast cells to each CAD/CAM material was evaluated by scanning electron microscopy (SEM). The results showed that the two samples that were exposed to an acidic environment (CS and SN) induced a reduction of mitochondrial activity and plasma membrane damage as regards the fibroblast cells. A similar effect was observed in TC_fine-exposed material, which seemed to induce necrosis at the tested concentration of 1 mg/mL. No oxidative stress was observed in fibroblasts and keratinocytes treated with the CAD/CAM materials. Regarding the adhesion degree, it was found that the fibroblasts adhere to all the occlusal veneers tested, with the mention that the CS and SN materials have a weaker adhesion with fewer cytoplasmic extensions than TC material. With all of this considered, the CAD/CAM restorative materials tested are biocompatible and represent support for the attachment and dispersion of cells.

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer–liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells.

This study presents the correct processing of Co–Cr alloys as a method of preserving the properties of the materials as-cast, and therefore they can be safely placed in contact with the oral cavity tissues as resistance frameworks. The basic materials analyzed in this study were five commercial Co–Cr dental alloys with different components obtained in three processing steps. The analysis of the electrochemical behavior at the surface of the Co–Cr alloys was performed by electrochemical measurements: impedance spectroscopy (EIS), open circuit electrical potential (OCP), and linear polarization (LP). In terms of validation, all five alloys had a tendency to generate a stable oxide layer at the surface. After the measurements and the graphical representation, the alloy that had a higher percentage of tungsten (W) and iron (Fe) in composition showed a higher tendency of anodizing. After the application of the heat treatment, the disappearance of the hexagonal phase was observed, with the appearance of new phases of type (A,B)2O3 corresponding to some oxide compounds, such as Fe2O3, Cr2O3, (Cr,Fe)2O3, and CoMnO3. In conclusion, the processing of Co–Cr alloys by melting and casting in refractory molds remains a viable method that can support innovation, in the context of technology advance in recent years towards digitalization of the manufacturing process, i.e., the construction of prosthetic frameworks conducted by additive methods using Co–Cr powder alloy.

Biocompatible gel microemulsions containing natural origin excipients are promising nanocarrier systems for the safe and effective topical application of hydrophobic drugs, including antifungals. Recently, to improve fluconazole skin permeation, tolerability and therapeutic efficacy, we developed topical biocompatible microemulsions based on cinnamon, oregano or clove essential oil (CIN, ORG or CLV) as the oil phase and sucrose laurate (D1216) or sucrose palmitate (D1616) as surfactants, excipients also possessing intrinsic antifungal activity. To follow up this research, this study aimed to improve the adhesiveness of respective fluconazole microemulsions using chitosan (a biopolymer with intrinsic antifungal activity) as gellator and to evaluate the formulation variables’ effect (composition and concentration of essential oil, sucrose ester structure) on the gel microemulsions’ (MEGELs) properties. All MEGELs were evaluated for drug content, pH, rheological behavior, viscosity, spreadability, in vitro drug release and skin permeation and antifungal activity. The results showed that formulation variables determined distinctive changes in the MEGELs’ properties, which were nevertheless in accordance with official requirements for semisolid preparations. The highest flux and release rate values and large diameters of the fungal growth inhibition zone were produced by formulations MEGEL-FZ-D1616-CIN 10%, MEGEL-FZ-D1216-CIN 10% and MEGEL-FZ-D1616-ORG 10%. In conclusion, these MEGELs were demonstrated to be effective platforms for fluconazole topical delivery.

The in vivo distribution of 50 nm clusters of polyethylene glycol-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-PEG) was conducted in this study. SPIONs-PEG were synthesized de novo, and their structure and paramagnetic behaviors were analyzed by specific methods (TEM, DLS, XRD, VSM). Wistar rats were treated with 10 mg Fe/kg body weight SPIONs-PEG and their organs and blood were examined at two intervals for short-term (15, 30, 60, 180 min) and long-term (6, 12, 24 h) exposure evaluation. Most exposed organs were investigated through light and transmission electron microscopy, and blood and urine samples were examined through fluorescence spectrophotometry. SPIONs-PEG clusters entered the bloodstream after intraperitoneal and intravenous administrations and ended up in the urine, with the highest clearance at 12 h. The skin and spleen were within normal histological parameters, while the liver, kidney, brain, and lungs showed signs of transient local anoxia or other transient pathological affections. This study shows that once internalized, the synthesized SPIONs-PEG disperse well through the bloodstream with minor to nil induced tissue damage, are biocompatible, have good clearance, and are suited for biomedical applications.

The electrospun nanosystems containing poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and 1 wt% Fe doped ZnO nanoparticles (NPs) (with the content of dopant in the range of 0–1 wt% Fe) deposited onto polylactic acid (PLA) film were prepared for food packaging application. They were investigated by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), antimicrobial analysis, and X-ray photoelectron spectrometry (XPS) techniques. Migration studies conducted in acetic acid 3% (wt/wt) and ethanol 10% (v/v) food simulants as well as by the use of treated ashes with 3% HNO3 solution reveal that the migration of Zn and Fe falls into the specific limits imposed by the legislation in force. Results indicated that the PLA/PHBV/ZnO:Fex electrospun nanosystems exhibit excellent antibacterial activity against the Pseudomonas aeruginosa (ATCC-27853) due to the generation of a larger amount of perhydroxyl (˙OOH) radicals as assessed using electron paramagnetic resonance (EPR) spectroscopy coupled with a spin trapping method.

The detection of folic acid in biological samples or pharmaceutical products is of great importance due to its implications in the biological functions of the human body, along with the development and growth of the fetus. The deficiency of folic acid can be reversed by the intake of different pharmaceutical formulations or alimentary products fortified with this molecule. The elaboration of sensing platforms represents a continuous work in progress, a task in which the use of conductive polymers modified with different functionalities represents one of the outcoming strategies. The possibility of manipulating their morphology with the use of templates or surfactants represents another advantage. A sensing platform based on carboxylic functionalized polypyrrole was synthesized via the electrochemical approach in the presence of a polymeric surfactant on a graphite-based surface. The sensor was able to detect the folic acid from 2.5 μM to 200 μM with a calculated limited of detection of 0.8 μM. It was employed for the detection of the analyte from commercial human serum and pharmaceutical products with excellent recovery rates. The results were double checked using an optimized spectrophotometric procedure that confirmed furthermore the performances of the sensor related to real samples assessment.

Raman mapping is becoming a very useful tool in investigating cells and cellular components, as well as bioactive molecules intracellularly. In this study, we have encapsulated beta-carotene using a layer-by-layer technique, as a way to enhance its stability and bioavailability. Further, we have used Raman mapping to characterize the as-obtained capsules and monitor their uptake by the human retinal epithelial D407 cells. We were able to successfully map the beta-carotene distribution inside the capsules, to localize the capsules intracellularly, and distinguish between capsules and other cellular components.

Medicinal plants are often used as reducing agents to prepare metal nanoparticles through green-synthesis due to natural compounds and their potential as chemotherapeutic drugs. Thus, three types of eco-friendly Ag-MnO2 nanoparticles (Ag-MnO2NPs) were synthesized using C. majus (CmNPs), V. minor (VmNPs), and a 1:1 mixture of the two extracts (MNPs). These NPs were characterized using S/TEM, EDX, XRD, and FTIR methods, and their biological activity was assessed in vitro on normal keratinocytes (HaCaT) and skin melanoma cells (A375). All synthesized NPs had manganese oxide in the middle, and silver oxide and plant extract on the exterior. The NPs had different forms (polygonal, oval, and spherical), uniformly distributed, with crystalline structures and different sizes (9.3 nm for MNPs; 10 nm for VmNPs, and 32.4 nm for CmNPs). The best results were obtained with VmNPs, which reduced the viability of A375 cells up 38.8% and had a moderate cytotoxic effect on HaCaT (46.4%) at concentrations above 500 µg/mL. At the same concentrations, CmNPs had a rather proliferative effect, whereas MNPs negatively affected both cell lines. For the first time, this paper proved the synergistic action of the combined C. majus and V. minor extracts to form small and uniformly distributed Ag-MnO2NPs with high potential for selective treatments.

Currently, research studies on nanoparticle cytotoxicity, uptake or internalization into the body’s cells are of great interest for the improvement of diagnostic and therapeutic applications. We report here the synthesis and characterization of very stable novel warfarin-capped gold nanoparticles with an average diameter of 54 ± 10 nm which were prepared using sodium warfarin as a reducing agent. The nanoparticles were tested in terms of cytotoxicity and cellular internalization in vitro on two cell lines: normal lung fibroblast HFL-1 and human retinal pigment epithelial D407 cells. Our results showed that the normal lung fibroblast HFL-1 cells were more sensitive to the nanoparticle treatment compared to the human retinal pigment epithelial D407 cells. Moreover, any signs of potential cytotoxicity occurred during the first 24 h of treatment, the cellular viability remaining largely unchanged for longer exposure times. Transmission electron microscopy and dark field hyperspectral imaging revealed that the nanoparticles were effectively delivered and released to the HFL-1 and D407 cells’ cytoplasm. Our results provide valuable information to further investigate sodium warfarin-capped gold nanoparticles for possible biological applications.

We present the case of a 51-year-old male with known congestive heart failure and acute myocarditis who presented to the emergency department (ED) with swollen testicles and urinary symptoms two weeks after the initiation of sodium glucose cotransporter 2 (SGLT2) inhibitor treatment. Abdominal and pelvic computed tomography (CT) scan was consistent with the diagnosis of Fournier’s gangrene (FG). Intravenous antibiotics were administered and surgical exploratory intervention and excision of necrotic tissue were performed, stopping the evolution of necrotizing fasciitis. FG, a reported adverse event, may rarely occur when SGLT2 inhibitors are administered in patients with diabetes. To our knowledge, there have been no reported cases of FG in Romania since SLGT2 inhibitors were approved. The distinguishing feature of this case is that the patient was not diabetic, which emphasizes that patients without diabetes who are treated for heart failure with SGLT2 inhibitors may also be at risk of developing genitourinary infections. The association of predisposing factors may have contributed to the development of FG in this case and even though the benefits of SGLT2 inhibitors outweigh the risks, serious adverse events need to be voluntarily reported in order to intervene promptly, verify the relationship, and minimize the risk of bias.