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Background and objectives Heart failure (HF) significantly influences the quality of life, both physically and emotionally, as well as social and environmental relationships. One major objective of HF treatment is to maintain or improve the quality of life. The aims of the study were to assess the impact of HF on social relationships and the relationship with the environment, according to therapeutic class and the presence of comorbidities, and to identify predictive factors for the impairment of these dimensions of the quality of life. Materials and methods This study was based on a cross-sectional survey; 252 patients with HF who have referred themselves to the medical rehabilitation department of the "Avram Iancu" Clinical Hospital, Oradea, between February 2023 and February 2024 were included. The patients were divided into two groups (Group HF-S/V, patients undergoing treatment with sacubitril/valsartan; Group HF-CT, patients receiving conventional therapy). All patients were asked to complete two assessment tools: the Charlson Comorbidity Index (CCI) questionnaire and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire. Results The mean values obtained per the domain of social relationships were significantly better for Group HF-CT (65.762 ± 12.519 versus 61.266 ± 12.428, p = 0.024). The mean values obtained on the domain of social relations and in relation to the environment were significantly better for Group HF-CT (65.762 ± 12.519 versus 61.266 ± 12.428, p = 0.024; 61.333 ± 13.461 versus 51.719 ± 16.769, p < 0.001). Both dimensions of the quality of life correlate with age and CCI (F = 7.793, p < 0.001, for social relationships; F = 16.821, p < 0.001, for relationship with the environment). Conclusions Social relationships and the relationship with the environment are affected in HF patients and correlate with age and comorbidity index, regardless of the type of therapy.
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[This corrects the article DOI: 10.3389/fphar.2022.1015835.].
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Metabolic syndrome represents a cluster of conditions, such as abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, that are highly prevalent in developed countries because of unhealthy lifestyles [...].
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Metabolic Syndrome , Metabolic Syndrome/metabolism , Humans , AnimalsABSTRACT
Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients.
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Ekbom syndrome, also known as delusional parasitosis (DP) or delusional infestation, is an uncommon psychiatric disorder distinguished by an enduring conviction of parasitic infestation, persisting notwithstanding the presence of medical evidence to the contrary. Primarily affecting middle-aged women, DP can manifest either as isolated psychological distress or as a component within a more intricate psychiatric framework, substantially influencing the quality of life for affected individuals. Its pathophysiological mechanism involves uncertain dopaminergic imbalances and dysfunction in the dopamine transporter system. Dermatologists often play a pivotal role in diagnosis, as patients first seek dermatological assessments of their signs and symptoms. However, DP frequently originates from underlying psychiatric disorders or medical variables, manifesting with neurological and infectious causative factors. The diagnostic complexity is attributed to patients' resolute convictions, leading to delayed psychiatric intervention. First-line DP treatment involves antipsychotics, with newer agents demonstrating promising prospects, but the lack of standardized protocols poses a significant therapeutic challenge. In this narrative review, both a comprehensive approach to this uncommon pathology and an update on the state of knowledge in this medical subfield focused on optimizing the management of DP are provided. The complexity of DP underlying its uncommon nature and the incomplete understanding of its pathophysiology highlight the need for further research through multicenter studies and multidisciplinary teams to enhance therapeutic efficacy and safety.
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Antipsychotic Agents , Delusional Parasitosis , Middle Aged , Humans , Female , Quality of Life , Delusional Parasitosis/diagnosis , Delusional Parasitosis/drug therapy , Delusional Parasitosis/psychology , Antipsychotic Agents/therapeutic use , Dopamine/therapeutic use , Interdisciplinary StudiesABSTRACT
To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling.
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Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate excessive sebum production and follicular cell proliferation, leading to acne lesions. Similarly, thyroid hormone imbalances affect sebaceous gland activity, epidermal lipid composition, and skin cell turnover, impacting acne occurrence and severity. This study aimed to assess the potential contribution of metabolic and endocrine preconditions to acne development. A total of 389 patients diagnosed with acne were included and divided into three groups: the metabolic precondition group (MPG, N = 163, 41.9%), the endocrine precondition group (EPG, N = 162, 41.65%), and the control group (CG, N = 89, 22.88%). Data related to the degree of acne severity and comorbidities of interest were collected from the patients' medical records. In the groups with concomitant diseases, moderate and severe acne were significantly more prevalent (56.44% and 41.10% in MPG, and 35.80% and 61.11% in EPG) compared to the control group (5.61% and 4.89%). The most prevalent preconditions observed were insulin resistance syndrome in MPG (63.8%) and autoimmune thyroiditis in EPG (95.06%). Significant age-related differences in acne severity were found across all study groups (p < 0.05). In MPG, the age variable was significantly higher in the presence of mild acne, while in EPG, the age variable was significantly lower for the mild acne group. A positive association was observed between the severity of acne and insulin resistance syndrome, obesity, autoimmune thyroiditis, and hypothyroidism (p < 0.05). Risk analysis indicated a significantly higher risk (RR > 1, 95% CI RR > 1, p < 0.001) of developing moderate and severe acne in the presence of these preconditions. The presence of both metabolic and endocrine preconditions significantly increased the likelihood of developing severe acne, leading to the hypothesis that both conditions may be contributing factors to the development of acne.
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Acne Vulgaris , Hashimoto Disease , Insulin Resistance , Metabolic Syndrome , Thyroid Diseases , Thyroiditis, Autoimmune , Humans , Risk Assessment , ObesityABSTRACT
Patients with ulcerative colitis (UC) are reported to have changes in body structure, with negative impact on the course of disease. This study explored the effects of a standardized nutritional supplement containing five bacterial strains of at least five billion bacteria (Bifidobacterium infantis, Bifidobacterium animalis, Lactobacillus bulgaricus, Lactobacillus helveticus, and Enterococcus faecium), L-glutamine, and biotin on the body composition and quality of life of patients with UC. Ninety-three patients over 18 years of age with a confirmed diagnosis of UC, for whom body composition could be accurately determined, were included in this observational follow-up randomized study. These patients were split into two groups: UC-P (44 patients with dietary counselling and supplement with probiotics) and UC-NP (49 patients with dietary counselling, without supplement). Body composition was assessed using the multifrequency bioelectrical impedance device, and the quality of life related to UC was evaluated by applying the short inflammatory bowel disease questionnaire (SIBDQ). The results showed that the average value of muscular mass (MM) and sarcopenic index (SMI) significantly increased (p = 0.043, respectively, p = 0.001) and a large fraction (p = 0.001) of patients had their SMI levels normalized in the UC-P group compared with UC-NP group. The extracellular water to total body water ratio (ECW/TBW) also had significantly different mean values (p = 0.022), favoring the UC-P group. By testing the differences between the average values of body composition parameters before and after treatment, we obtained significant results in body mass index (BMI) (p = 0.046), fat free mass (FFM) (p < 0.001), and ECW/TBW ratio (p = 0.048). The SIBDQ total score increased significantly (p < 0.001) in the UC-P group and was more strongly associated with changes in body parameters. Supplementation with probiotics associated with L-glutamine and biotin can improve body composition parameters, which in turn implies an increase in the overall quality of life of patients with UC.
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Colitis, Ulcerative , Inflammatory Bowel Diseases , Probiotics , Humans , Adolescent , Adult , Colitis, Ulcerative/drug therapy , Biotin/therapeutic use , Glutamine/therapeutic use , Quality of Life , Probiotics/therapeutic use , Dietary Supplements , Body Composition , Inflammatory Bowel Diseases/complicationsABSTRACT
Since the earliest times, essential oils (EOs) have been utilized for medicinal and traditional purposes. However, in recent decades, an increasing interest has developed due to the need to rediscover herbal remedies and adjuvant therapies for the management of various diseases, particularly chronic ones. The present narrative review examines the potential for EOs to exert hypoglycemic and antioxidant effects in diabetes mellitus, analyzing the main publications having evaluated plant species with potentially beneficial effects through their phytocompounds in diabetes mellitus and its complications. Numerous species have shown promising characteristics that can be used in diabetes management. The hypoglycemic effects of these EOs are attributed to their capacity to stimulate glucose uptake, suppress glucose production, and increase insulin sensitivity. Moreover, EOs can alleviate the oxidative stress by manifesting their antioxidant effects via a variety of mechanisms, including the scavenging of free radicals, the regulation of antioxidant enzymes, and the decreasing of lipid peroxidation, due to their diverse chemical composition. These findings demonstrate the possible benefits of EOs as adjuvant therapeutic agents in the management of diabetes and its complications. The use of EOs in the treatment of diabetes shows good potential for the development of natural and effective strategies to enhance the health outcomes of people with this chronic condition, but additional experimental endorsements are required.
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Diabetes Mellitus, Experimental , Oils, Volatile , Humans , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Oils, Volatile/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Oxidative Stress , Diabetes Mellitus, Experimental/drug therapyABSTRACT
(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time-kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 µg GAE/mgE) and flavonoid contents (9.93 ± 0.5 µg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20-40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60-100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR.
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Cross-sectional studies, while not considered glamorous endeavors, are firmly anchored in data and statistics, providing essential insights about public health. The aim of the study is to see the frequency of hepatoprotective (HP) nutritional supplement consumption among patients with chronic diseases (other than chronic liver disorders) and analyzes the habits related to the consumption of nutritional supplements among these patients. A total of 954 patients, seeking medical prescriptions for chronic diseases under various payment arrangements (compensated, gratuity, or full payment) were carefully selected over a 12-month period from four private pharmaceutical facilities. We examined the frequency of HP consumption in relation with a number of prescribed medications for chronic conditions. All these patients were invited to complete a questionnaire about their supplement consumption habits and were provided the option to participate in a nutritional status assessment. One hundred ninety-five patients consented to participate in the survey, and 65 patients agreed to undergo a nutritional status evaluation. Of the 954 patients, 77.2% incorporate HP into their regimen. The most frequent consumption (83.33%) was recorded in a group with seven drugs, followed by a group with three drugs (82.84%). Women have a higher usage rate of HP (80.58%; 444 from 551) compared to men (62.60%; 293 from 383), and most of the patients (59.5%) used extracts of Silybum marianum L. In the survey, 64.61% of participants were using supplements, with most (59.52%) consuming HP. Only 32.54% of patients rely on recommendations from healthcare professionals. Of the patients who use supplements, 55.56% reported improvements in their health status. Furthermore, patients who integrate supplements into their daily routine tend to achieve better overall nutritional status.
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Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols are primarily known for their anti-inflammatory and antioxidant properties, but they can also modify the gut microbiota. According to recent research, polyphenols positively influence the gut microbiota, which regulates metabolic responses and reduces systemic inflammation. This review emphasizes the prebiotic role of polyphenols and their impact on specific gut microbiota components in patients at cardiometabolic risk. It also analyzes the most recent research on the positive effects of polyphenols on cardiometabolic health. While numerous in vitro and in vivo studies have shown the interaction involving polyphenols and gut microbiota, additional clinical investigations are required to assess this effect in people.
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The occurrence of pustules, comedones, nodules, and cysts defines acne vulgaris, a prevalent chronic inflammatory dermatological condition. In the past few decades, essential oils extracted from varied natural sources have acquired recognition due to their potential medicinal applications in acne therapy. However, there is not yet sufficient medical data to fully characterize this interaction. Multiple factors contribute to the development of acne vulgaris, including excessive sebaceous production, inflammatory processes, hyperkeratinization, and infection with Cutibacterium acnes. Essential oils, including oregano, lavender, lemon grass, myrtle, lemon, thyme, eucalyptus, rosemary, and tea tree, have been found to possess anti-inflammatory, antioxidant, and antimicrobial properties, which may target the multifactorial causes of acne. Analytical methods for determining antioxidant potential (i.e., total phenolic content, diphenyl-1-picrylhydrazyl free radical scavenging assay, reducing power assay, ferrous ion chelating activity, thiobarbituric acid reactive species assay, ß-carotene bleaching assay, etc.) are essential for the evaluation of these essential oils, and their method optimization is crucial. Further studies could include the development of novel acne treatments incorporating essential oils and an assessment of their efficacy in large clinical trials. In addition, further research is necessary to ascertain the mechanisms of action of essential oils and their optimal doses and safety profiles for optimal implementation in the management of acne vulgaris.
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Acne Vulgaris , Citrus , Oils, Volatile , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Acne Vulgaris/drug therapy , Biological AssayABSTRACT
Ophthalmic disorders consist of a broad spectrum of ailments that impact the structures and functions of the eye. Due to the crucial function of the retina in the vision process, the management of eye ailments is of the utmost importance, but several unmet needs have been identified in terms of the outcome measures in clinical trials, more proven minimally invasive glaucoma surgery, and a lack of comprehensive bibliometric assessments, among others. The current evaluation seeks to fulfill several of these unmet needs via a dual approach consisting of a molecular docking analysis based on the potential of ripasudil and fasudil to inhibit Rho-associated protein kinases (ROCKs), virtual screening of ligands, and pharmacokinetic predictions, emphasizing the identification of new compounds potentially active in the management of glaucoma, and a comprehensive bibliometric analysis of the most recent publications indexed in the Web of Science evaluating the management of several of the most common eye conditions. This method resulted in the finding of ligands (i.e., ZINC000000022706 with the most elevated binding potential for ROCK1 and ZINC000034800307 in the case of ROCK2) that are not presently utilized in any therapeutic regimen but may represent a future option to be successfully applied in the therapeutic scheme of glaucoma following further comprehensive testing validations. In addition, this research also analyzed multiple papers listed in the Web of Science collection of databases via the VOSviewer application to deliver, through descriptive analysis of the results, an in-depth overview of publications contributing to the present level of comprehension in therapeutic approaches to ocular diseases in terms of scientific impact, citation analyses, most productive authors, journals, and countries, as well as collaborative networks. Based on the molecular docking study's preliminary findings, the most promising candidates must be thoroughly studied to determine their efficacy and risk profiles. Bibliometric analysis may also help researchers set targets to improve ocular disease outcomes.
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Ocular diseases can significantly impact vision and quality of life through pathophysiological alterations to the structure of the eye. The management of these conditions often involves a combination of pharmaceutical interventions, surgical procedures, and laser therapy. Laser technology has revolutionized many medical fields, including ophthalmology, offering precise and targeted treatment options that solve some of the unmet needs of other therapeutic strategies. Conventional laser techniques, while effective, can generate excessive thermal energy, leading to collateral tissue damage and potential side effects. Compared to conventional laser techniques, micropulse laser therapy delivers laser energy in a pulsed manner, minimizing collateral damage while effectively treating target tissues. The present paper highlights the advantages of micropulse laser therapy over conventional laser treatments, presents the implications of applying these strategies to some of the most prevalent ocular diseases, and highlights several types and mechanisms of micropulse lasers. Although micropulse laser therapy shows great potential in the management of ocular diseases, further research is needed to optimize treatment protocols, evaluate long-term efficacy, and explore its role in combination therapies.
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Eye Diseases , Laser Therapy , Low-Level Light Therapy , Humans , Quality of Life , Eye Diseases/surgery , Disease ManagementABSTRACT
BACKGROUND: Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health. METHODOLOGY: This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches. RESULTS: Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). CONCLUSION: The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.
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Antioxidants , Nitric Oxide , Rats , Animals , Antioxidants/therapeutic use , Nitric Oxide/pharmacology , Molecular Docking Simulation , Plant Extracts/pharmacology , Rats, Sprague-Dawley , Oxidative Stress , Anti-Inflammatory Agents/pharmacology , Phenols/pharmacologyABSTRACT
Cancer is one of the most widespread and severe diseases with a huge mortality rate. In recent years, the second-leading mortality rate of any cancer globally has been breast cancer, which is one of the most common and deadly cancers found in women. Detecting breast cancer in its initial stages simplifies treatment, decreases death risk, and recovers survival rates for patients. The death rate for breast cancer has risen to 0.024 % in some regions. Sensitive and accurate technologies are required for the preclinical detection of BC at an initial stage. Biomarkers play a very crucial role in the early identification as well as diagnosis of women with breast cancer. Currently, a wide variety of cancer biomarkers have been discovered for the diagnosis of cancer. For the identification of these biomarkers from serum or other body fluids at physiological amounts, many detection methods have been developed. In the case of breast cancer, biomarkers are especially helpful in discovering those who are more likely to develop the disease, determining prognosis at the time of initial diagnosis and choosing the best systemic therapy. In this study we have compiled various clinical aspects and signaling pathways associated with protein-based biomarkers and gene-based biomarkers.
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Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Biomarkers, TumorABSTRACT
Rheumatoid arthritis (RA) is a heterogeneous inflammatory disease with an autoimmune origin and an incompletely elucidated pathophysiological mechanism. RA pharmacotherapy is based on chemically or biologically active substances that provide clinical alleviation and remission, but the disease is still incurable. As a result, there remains a need for significant therapeutic development, and adjuvant therapies may play an essential role in the search for novel RA treatment strategies. The aim of the present study was to investigate potential phytocompounds and phytocompound derivates as RA treatment agents, using in silico methodologies. In this regard, five phytoconstituents identified in different structures of Embelia ribes were evaluated by in silico methods for their potential action on target proteins of therapeutic interest in RA. The methodology involved identifying the phytocompound with the highest binding toward the target protein via molecular docking using AutoDock Vina 1.5.7, followed by a ligand-based virtual screening based on the structure of the most promising phytocompound using SwissSimilarity. This process led to the identification of ligands that are not currently utilized in medical practice, but that might have the potential to be used in the management of RA after further extensive experimental endorsements. ZINC000004024651 showed the highest binding affinity for the Bruton's tyrosine kinase protein, followed by ZINC000000434197 for p38 mitogen-activated protein kinases, ZINC000087606977 for interleukin-1 receptor-associated kinase 4, and ZINC000014728393 for matrix metallopeptidase 9, the latter two showing higher affinity than the co-crystallized compound. The relatively high affinities to target proteins and the pharmacokinetic data obtained by in silico studies using SwisADME suggest a first step for the inclusion of promising new compounds in various more advanced studies, leading to the evaluation of efficacy and safety profiles.
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Rheumatoid arthritis (RA) is a debilitating autoimmune disorder with an inflammatory condition targeting the joints that affects millions of patients worldwide. Several unmet needs still need to be addressed despite recent improvements in the management of RA. Although current RA therapies can diminish inflammation and alleviate symptoms, many patients remain unresponsive or experience flare-ups of their ailment. The present study aims to address these unmet needs through in silico research, with a focus on the identification of novel, potentially active molecules. Therefore, a molecular docking analysis has been conducted using AutoDockTools 1.5.7 on Janus kinase (JAK) inhibitors that are either approved for RA or in advanced phases of research. The binding affinities of these small molecules against JAK1, JAK2, and JAK3, which are target proteins implicated in the pathophysiology of RA, have been assessed. Subsequent to identifying the ligands with the highest affinity for these target proteins, a ligand-based virtual screening was performed utilizing SwissSimilarity, starting with the chemical structures of the previously identified small molecules. ZINC252492504 had the highest binding affinity (-9.0 kcal/mol) for JAK1, followed by ZINC72147089 (-8.6 kcal/mol) for JAK2, and ZINC72135158 (-8.6 kcal/mol) for JAK3. Using SwissADME, an in silico pharmacokinetic evaluation showed that oral administration of the three small molecules may be feasible. Based on the preliminary results of the present study, additional extensive research is required for the most promising candidates to be conducted so their efficacy and safety profiles can be thoroughly characterized, and they can become medium- and long-term pharmacotherapeutic solutions for the treatment of RA.
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Arthritis, Rheumatoid , Autoimmune Diseases , Janus Kinase Inhibitors , Humans , Janus Kinase Inhibitors/pharmacology , Janus Kinase Inhibitors/therapeutic use , Molecular Docking Simulation , Arthritis, Rheumatoid/drug therapy , Autoimmune Diseases/drug therapy , Inflammation/drug therapy , Janus Kinase 2 , Janus KinasesABSTRACT
BACKGROUND/AIM: The presence of tetracycline (TC) and its residues in raw milk and milk dairy products poses a threat to human health due to the induction of antibiotic resistance of bacteria that can be transmitted between animals, humans, and the environment. The aim of this study was to investigate the transfer of TC from raw milk to different dairy products: pasteurized milk, boiled milk, sour milk, skimmed milk, and cottage cheese. We analyzed samples of milk from different sources: household farmers, local farms, and milk factories. MATERIALS AND METHODS: The analyses of TC in milk and dairy products were performed using colloidal gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The highest content of TC was found in the milk purchased from local household farmers; therefore, these samples were chosen for the study of TC transfer to dairy products. TC was also found in sour milk at levels comparable with those obtained in raw milk. The average TC content decreased following heat treatment of the milk, as follows: for pasteurized milk 22.07% and for boiled milk 29.35%. The highest concentrations were determined in cottage cheese in the range 200-620 µg/kg. CONCLUSION: TC residues are transferred from milk to dairy products in various amounts depending on the preparation conditions, and due to their chemical properties, they accumulate in concentrated derivatives, such as cheese. Therefore, TC can be identified even in cheeses prepared from milk with undetected antibiotic levels.