Search Results (25,646)

Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was proposed to increase the therapeutic effect of this plant. Salvia officinalis ethanolic extract was prepared and analyzed by HPLC/UV-DAD and encapsulated in a matrix based on gelatin and pectin using an emulsion–coacervation process. The prepared microcapsules were analyzed by laser particle size, optical microscopy, in vitro dissolution kinetics, and ex vivo bioadhesion. In order to determine the action mechanism of Salvia officinalis extract, in the treatment of gastric ulcer, the in vivo anti-ulcerogenic activity in rats, using the ulcer model induced by ethanol; the in vivo anti-Helicobacter pylori activity; and in vitro inhibitory activity of H⁺/K⁺-ATPase were carried out. These three biological activities were evaluated for ethanolic extract and microcapsules to determine the effect of formulation on biological activities. Ethanolic extract of Salvia officinalis was mainly composed of polyphenols (chlorogenic acid 7.43%, rutin 21.74%, rosmarinic acid 5.88%, and quercitrin 14.39%). Microencapsulation of this extract allowed us to obtain microcapsules of 104.2 ± 7.5 µm in diameter, an encapsulation rate of 96.57 ± 3.05%, and adequate bioadhesion. The kinetics of in vitro dissolution of the extract increase significantly after its microencapsulation. Percentages of ulcer inhibition for 100 mg/kg of extract increase from 71.71 ± 2.43% to 89.67 ± 2.54% after microencapsulation. In vitro H⁺/K⁺-ATPase-inhibiting activity resulted in an IC50 of 86.08 ± 8.69 µM/h/mg protein for free extract and 57.43 ± 5.78 µM/h/mg protein for encapsulated extract. Anti-Helicobacter pylori activity showed a similar Minimum Inhibitory Concentration (MIC) of 50 µg/mL for the extract and microcapsules. Salvia officinalis ethanolic extract has a significant efficacy for the treatment of gastric ulcer; its mechanism of action is based on its gastroprotective effect, anti-Helicobacter pylori, and H⁺/K⁺-ATPase inhibitor. Moreover, the microencapsulation of this extract increases its gastroprotective and H⁺/K⁺-ATPase-inhibiting activities significantly. Full article

Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O₃), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating or reversing skin damage caused by environmental factors. Topical antioxidants containing a combination of l-ascorbic acid, tocopherol, and ferulic acid have significantly improved markers of skin health after exposure to environment-induced skin damage. However, research suggests that l-ascorbic acid and tocopherol tend to be relatively unstable, possibly affecting their efficacy against outdoor stressor damage. It has been shown that ferulic acid significantly improves the stability of both l-ascorbic acid and tocopherol, but its long-term stabilization effects on these antioxidants are relatively unknown. Material and Methods: This study evaluated the time-dependent effectiveness of a topical antioxidant mix containing 15% l-ascorbic acid, 1% tocopherol, and 0.5% ferulic acid (AOX) on UV-induced skin damage. Skin biopsies (12 mm, n = 60) were placed in a 6-well plate with medium and incubated at 37 °C and 5% CO₂ overnight. The day after, skin samples were pretreated with 10 µL of differently aged AOX (0-, 6-, 12-, and 36-month-old) and then exposed to different doses of UV light (100, 200, 400 mJ/cm²) daily over four days. AOX formulations were stored in a cool, dry, and dark place at approximately 20–22 °C during the whole study. This study evaluated 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as oxidative damage and skin DNA damage markers, Collagen1 and Filaggrin as skin structure, and IL-8 and Nrf2 as inflammatory and defensive response. Results: UV exposure significantly increased oxidative and inflammatory markers in human skin explants affecting also filaggrin and collagen levels. However, pre-treatment with the antioxidant formulation, particularly in its younger formulations (0-, 6-, and 12-month-old), significantly reduced the damaging effect of UV. Additionally, all antioxidant formulations effectively mitigated UV-induced damage across all doses. Conclusions: Our results indicate that pre-treatment with this formulation consistently reduces UV-induced oxidative damage and DNA damage in human skin explants, regardless of the formulation age and the discoloration state. Although effective, the protective capacity of aged formulations may be reduced only when extreme UV exposure is tested, a condition that is unlikely to occur under typical environmental conditions. These results support ferulic acid as a stabilization agent for topical antioxidant mixtures. Full article

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article

Endotoxins, lipopolysaccharides released from the outer membrane of Gram-negative bacteria, pose a significant risk in healthcare environments, particularly in Central Sterile Supply Departments (CSSDs), where the delivery of sterile pyrogen-free medical devices is critical for patient safety. Traditional methods for controlling endotoxins in water systems, such as ultraviolet (UV) disinfection, have proven ineffective at reducing endotoxin concentrations to comply with regulatory standards (<0.25 EU/mL). This limitation presents a significant challenge, especially in the context of reverse osmosis (RO) permeate used in CSSDs, where water typically has very low conductivity. Despite the established importance of endotoxin removal, a gap in the literature exists regarding effective chemical-free methods that can meet the stringent endotoxin limits in such low-conductivity environments. This study addresses this gap by evaluating the effectiveness of the eBooster™ electrochemical technology—featuring proprietary electrode materials and a reactor design optimized for potable water—for endotoxin removal from water, specifically under the low-conductivity conditions typical of RO permeate. Laboratory experiments using the B250 reactor achieved >90% endotoxin reduction (from 1.2 EU/mL to <0.1 EU/mL) at flow rates ≤5 L/min and current densities of 0.45–2.7 mA/cm². Additional real-world testing at three hospitals showed that the eBooster™ unit, when installed in the RO tank recirculation loop, consistently reduced endotoxin levels from 0.76 EU/mL (with UV) to <0.05 EU/mL over 24 months of operation, while heterotrophic plate counts dropped from 190 to <1 CFU/100 mL. Statistical analysis confirmed the reproducibility and flow-rate dependence of the removal efficiency. Limitations observed included reduced efficacy at higher flow rates, the need for sufficient residence time, and a temporary performance decline after two years due to a power fault, which was promptly corrected. Compared to earlier approaches, eBooster™ demonstrated superior performance in low-conductivity environments without added chemicals or significant maintenance. These findings highlight the strength and novelty of eBooster™ as a reliable, chemical-free, and maintenance-friendly alternative to traditional UV disinfection systems, offering a promising solution for critical water treatment applications in healthcare environments. Full article

Background: Exposure-based cognitive behavioral therapy (Ex-CBT) is widely seen as the gold-standard treatment for anxiety and obsessive-compulsive disorder (OCD). Yet, minoritized youth are underrepresented in efficacy studies, raising questions about the applicability of Ex-CBT to minoritized youth. Effectiveness data suggest systematic adaptation of Ex-CBT to address youth culture and context is likely needed, and many clinicians make adaptations and augmentations in practice. However, research on the specific strategies clinicians use to address their youth clients’ culture and context within anxiety and OCD treatment is lacking. In the current study, we assess practice-based adaptations, augmentations, and process-based approaches utilized when delivering treatment to youth for OCD and anxiety in public mental health clinics. Methods: We conducted qualitative interviews with 16 clinicians from both specialty anxiety and general mental health clinics serving youth with anxiety or OCD in the public mental health system. Participating clinicians had a mean age of 32.19 (SD = 5.87) and 69% of therapists identified as female; 69% identified as White, 25% identified as Asian, and 6% as Black or African American. In qualitative interviews, clinicians shared how they addressed clients’ culture and context (e.g., social identities, stressors and strengths related to social identities and lived environment). Thematic analysis identified the strategies clinicians employed to address culture and context. Results: Clinicians reported incorporating culture and context through process-based approaches (e.g., building trust gradually, considering clients’ social identity stressors, engaging in self-awareness to facilitate cultural responsiveness) and through culturally adapting and augmenting treatment to promote person-centered care. Core strategies included proactive and ongoing assessment of clients’ cultural and contextual factors, adapting exposures and augmenting Ex-CBT with strategies such as case management and discussion of cultural context, and taking a systems-informed approach to care. Conclusions: Examining practice-based adaptations, augmentations, and process-based approaches to treatment for minoritized youth with OCD or anxiety can inform efforts to understand what comprises person-centered culturally responsive Ex-CBT. Empirical testing of identified strategies is a needed area of future research. Full article

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their antibacterial and anti-biofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) in combination with ampicillin sodium (AS) were analyzed. The PNPs had an average particle diameter of 118.0 nm, a polydispersity index of 0.129, and a zeta potential of −28.2 mV. The fractional inhibitory concentration indices of PNPs and AS against tested MRSA strains highlighted this synergy, ranging between 0.375 and 0.5. Crystal violet staining showed that combined PNPs and AS significantly inhibited biofilm formation and reduced existing biofilm biomass. We then discovered that PNPs inhibited bacterial adhesion, extracellular polysaccharide synthesis, and mecR1, mecA, blaZ, and icaADBC gene expression. These results indicated that PNPs exerted a synergistic antibacterial effect with AS by inhibiting mecR1, mecA, and blaZ gene expressions to reduce the drug resistance of MRSA. Meanwhile, PNPs weakened bacterial adhesion and aggregation by suppressing icaADBC gene expression, allowing antibiotics to penetrate the biofilm, and exhibiting significant synergistic anti-biofilm activity. In summary, PNPs are promising candidates for combating MRSA-related diseases. Full article

Superficial fungal infections of the feet, such as tinea pedis and onychomycosis, are highly prevalent and frequently recurrent, often due to persistent contamination of footwear, textiles, and foot care instruments. Despite growing concern over antifungal resistance, environmental sources of reinfection remain under-recognized in clinical practice. This review critically examines historical and contemporary methods used to sanitize shoes, socks, podiatric tools, and related materials. Evidence from peer-reviewed studies published between 1938 and 2025 was analyzed across multiple disinfection categories, including chemical agents, thermal methods, laundering, ultraviolet- and ozone-based technologies, antimicrobial textiles, and sterilization protocols. Findings reveal a range of efficacies, limitations, and practical considerations across methods, with steam sterilization emerging as the most reliable for reusable instruments. A multifaceted approach combining pharmacologic treatment with consistent environmental hygiene is essential for breaking reinfection cycles and reducing antifungal resistance. This review highlights the need for clinical education and research into scalable, effective disinfection strategies. Full article

Background: This study aimed to evaluate the efficacy and safety of Noofen^® (Phenibut) in patients with Adjustment Disorder (AjD) and to assess the usability of the ADNM-20 (Adjustment Disorder New Module 20-item questionnaire) in routine clinical practice. This is the first study of Noofen^® in patients with AjD conducted in Latvia, and it also represents one of the first implementations of the ADNM-20 scale in routine clinical settings, where its applicability has not yet been widely established. Methods: A non-interventional observational study was conducted across several general practice offices in Latvia. Patients aged 18–70 with clinical symptoms of AjD, an ADNM-20 total score ≥ 30, and a new prescription for Noofen^® 250 mg three times daily for at least three weeks (per routine practice) were included. Exclusion criteria ruled out concomitant psychiatric or severe somatic conditions and use of medications or interventions that could affect AjD symptoms. Patients completed the ADNM-20 before and after treatment, and score changes were evaluated. Results: Ninety patients (65 women, 25 men; mean age 48 ± 12 years) completed the study. At baseline, 56.7% had high AjD symptom severity, with work-related stressors most frequently reported as triggers. After three weeks of Noofen^® treatment, ADNM-20 total scores decreased significantly (mean reduction 14.8 ± 11.3 points, p < 0.001), with greater improvement in core vs. accessory symptoms. Symptom severity shifted, with the proportion of high-severity patients decreasing 2.5-fold, and 14.4% scoring below the AjD diagnostic threshold post-treatment. Noofen^® was well tolerated. ADNM-20 showed good sensitivity to symptom change but remained vulnerable to human error during scoring. Conclusions: Noofen^® significantly reduced AjD symptoms, particularly sleep disturbance, restlessness, and anxiety, and was well tolerated. The ADNM-20 questionnaire proved useful in clinical practice and should be considered for routine use to better recognize and monitor AjD. Full article

Objectives: This study evaluated the therapeutic potential of topical Ripasudil hydrochloride hydrate in managing various forms of corneal edema. Methods: This retrospective study included 96 patients of 72.20 ± 10.52 years, with 53 females (55.2%) who were treated with Ripasudil for corneal edema, with a mean treatment duration of 5.2 ± 2.3 months, divided into four groups: post-cataract surgery (n = 32), Fuchs endothelial corneal dystrophy (FECD; n = 29), post-Descemet membrane endothelial keratoplasty (DMEK; n = 25), and post-penetrating keratoplasty (PKP; n = 10). All patients were treated with Ripasudil, typically administered three times daily in the first week and twice daily in the following months. Clinical efficacy outcomes were assessed using changes in best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) with specular microscopy, anterior segment optical coherence tomography (OCT), and slit-lamp examination, while intraocular pressure (IOP) was measured using the iCare tonometer. Results: Ripasudil treatment led to a reduction in CCT and improvement in visual acuity across most groups, with minimal changes in ECC. CCT decreased by 30.44 μm (p < 0.001), 25.56 μm (p < 0.001), 8.41 μm (p = 0.05), and 6.80 μm (p > 0.1); visual acuity improved by 0.27 (p = 0.001), 0.18 (p = 0.02), 0.17 (p = 0.025), and 0.07 logMAR units (p > 0.1); and ECC changed by +7.0 (p > 0.1), 15.4 (p > 0.1), −7.6 (p > 0.1), and 2.3 cells/mm² (p > 0.1) in the post-cataract surgery, FECD, post-DMEK, and post-PKP groups, respectively. Conclusions: No adverse events or progression of edema were recorded during the follow-up period. These findings support the role of Ripasudil as a non-invasive pharmacological approach to managing corneal edema and delaying or possibly avoiding surgical interventions, such as corneal transplantation, in selected cases. Full article

Ischemic heart disease (IHD) represents a leading cause of global morbidity and mortality. Despite significant advances in treatment achieved over recent decades, as well as various therapeutic strategies available to manage IHD progression currently, the global incidence of this disorder remains high. This review examines essential cell biology aspects of adenosine receptors (ARs), along with the effects of known synthetic small-molecule AR ligands, to provide an up-to-date view on the therapeutic potential towards IHD treatment. In particular, we report here advancements made on a selection of AR synthetic ligands that have demonstrated efficacy in pre-clinical or clinical studies, thereby holding promise as new therapeutic candidates in the field of IHD. Although this work adds further evidence that clinically valid small-molecule therapeutic agents targeting ARs exist, their use represents an emerging area, with most drug prototypes still in the pre-clinical developmental stage and many lacking large-scale clinical trials. The future lies in identifying improved AR synthetic ligands with enhanced efficacy and selectivity, as well as reduced adverse side effects, along with establishing a platform of specific and diversified pre-clinical tests, to inform in turn the resulting clinical investigations. Full article

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article

Neutrophils are increasingly recognized as key players in the tumor microenvironment (TME), displaying functional plasticity that enables them to either promote or inhibit cancer progression. Depending on environmental cues, tumor-associated neutrophils (TANs) may polarize toward antitumor “N1” or protumor “N2” phenotypes, exerting diverse effects on tumor growth, metastasis, immune modulation, and treatment response. While previous studies have focused on the pathological roles of TANs in cancer, less attention has been given to how cancer therapies themselves influence the behavior of TANs. This review provides a comprehensive synthesis of current knowledge regarding the dynamics of TANs in response to major cancer treatment modalities, including chemotherapy, radiotherapy, cell-based immunotherapies, and oncolytic viral and bacterial therapies. We discuss how these therapies influence TAN recruitment, polarization, and effector functions within the TME, and highlight key molecular regulators involved. By consolidating mechanistic and translational insights, this review emphasizes the potential to therapeutically reprogram TANs to enhance treatment efficacy. A deeper understanding of context-dependent TAN roles will be essential for developing more effective, neutrophil-informed cancer therapies. Full article

Epidermolysis Bullosa (EB) comprises a group of inherited blistering disorders caused by pathogenic variants in genes essential for skin and mucosal integrity. Nonsense mutations, which generate premature termination codons (PTCs), result in reduced or absent protein expression and contribute to severe disease phenotypes in EB. Readthrough therapies, which may continue translation past PTCs to restore full-length functional proteins, have emerged as promising approaches. This review summarizes findings from preclinical studies investigating readthrough therapies in EB models, clinical studies demonstrating efficacy in EB patients, and emerging readthrough agents with potential application to EB. Preclinical and clinical studies with gentamicin have demonstrated restored type VII collagen and laminin-332 expression, leading to measurable clinical improvements. Parallel development of novel compounds—including aminoglycoside analogs (e.g., ELX-02), translation termination factor degraders (e.g., CC-90009, SRI-41315, SJ6986), tRNA post-transcriptional inhibitors (e.g., 2,6-diaminopurine, NV848), and nucleoside analogs (e.g., clitocine)—has expanded the therapeutic pipeline. Although challenges remain regarding toxicity, codon specificity, and variable protein restoration thresholds, continued advances in molecular targeting and combination therapies offer the potential to establish readthrough therapies as localized or systemic treatments addressing both cutaneous and extracutaneous disease manifestations in EB. Full article

Oral mucositis (OM) is a severe inflammatory condition of the oral mucosa that is commonly associated with cancer therapies. Traditional treatments typically have limited efficacy and significant side effects, necessitating alternative approaches. Nanobased drug delivery systems (DDSs) present promising solutions, enhancing therapeutic outcomes while minimizing side effects. This review aims to evaluate the use of nanobased DDSs to treat OM. To reach these aims, an extensive literature review was conducted using the following databases: BVS, PubMed, Scopus, and Web of Science. The search strategy included the keywords “microparticles,” “nanoparticles,” “drug delivery system,” “oral mucositis,” “therapy,” and “treatment,” combined with the Boolean operators “AND” and “OR.” After applying filters for language, relevance, full-text availability, exclusion of review articles, and removal of duplicates, a total of 32 articles were selected for analysis. Of the 32 studies included in this review, 25 employed polymeric micro- or nanosystems for the treatment of OM. Regarding the stage of investigation, 10 studies were conducted in vitro, 16 were conducted in vivo, and 6 corresponded to clinical trials. Compared with conventional drug delivery approaches, most of these studies reported improved therapeutic outcomes. These findings highlight the potential of nanosystems as innovative strategies for enhancing OM treatment. Nonetheless, challenges in large-scale manufacturing, including reproducibility and safety, and the limited number of clinical trials warrant careful consideration. Future research with larger clinical trials is essential to validate these findings and effectively guide clinical practice. Full article