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1.
Sci Total Environ ; 951: 175723, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39181248

RESUMO

Combining single-species ecological modeling with advanced machine learning to investigate the long-term population dynamics of the rheophilic fish spirlin offers a powerful approach to understanding environmental changes and climate shifts in aquatic ecosystems. A new ESHIPPOClim model was developed by integrating climate change assessment into the ESHIPPO model. The model identifies spirlin as a potential early indicator of environmental changes, highlighting the interactive effects of climate change and anthropogenic stressors on fish populations and freshwater ecosystems. The ESHIPPOClim model reveals that 28.57 % of the spirlin's data indicates high resilience and ecological responsiveness, with 34.92 % showing medium-high adaptability, suggesting its substantial ability to withstand environmental stressors. With 36.51 % of the data in medium level and no data in the low category, spirlin may serve as a sentinel species, providing early warnings of environmental stressors before they severely impact other species or ecosystems. The results of uniform manifold approximation and projection (UMAP) and a decision tree show that pollution has the highest impact on the population dynamics of spirlin, followed by annual water temperature, overexploitation, and invasive species. Despite the obtained key drivers, higher abundance, dominance, and frequency values were detected in habitats with higher HIPPO stressors and climate change effects. Integrating state-of-the-art machine learning models has enhanced the predictive power of the ESHIPPOClim model, achieving approximately 90 % accuracy in identifying spirlin as an early indicator of climate change and anthropogenic stressors. The ESHIPPOClim model offers a holistic approach with broad practical applications using a simplified three-point scale, adaptable to various fish species, communities, and regions. The ecological modeling supported with advanced machine learning could serve as a foundation for rapid and cost-effective management of aquatic ecosystems, revealing the adaptability potential of fish species, which is crucial in rapidly changing environments.


Assuntos
Mudança Climática , Monitoramento Ambiental , Aprendizado de Máquina , Animais , Monitoramento Ambiental/métodos , Cyprinidae/fisiologia , Ecossistema , Dinâmica Populacional
2.
Curr Issues Mol Biol ; 46(8): 8981-8994, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39194748

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 µM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPARα and PPARγ protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74-86% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPARα, PPARγ, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPARα, PPARγ, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.

3.
Curr Issues Mol Biol ; 46(7): 6300-6314, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057018

RESUMO

With around one billion of the world's population affected, the era of the metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which to date there are almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it also affects extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn®) was approved for metabolic-dysfunction-associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Although the pharmaceutical industry is still lagging behind in developing an approved pharmacologic therapy for MAFLD, research has recently intensified and many molecules which are in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was approved via accelerated procedure for treatment of MAFLD, i.e., of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval.

4.
Ther Adv Vaccines Immunother ; 12: 25151355241264520, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39071998

RESUMO

Due to their high specificity and scalability, Monoclonal IgY antibodies have emerged as a valuable alternative to traditional polyclonal IgY antibodies. This abstract provides an overview of the production and purification methods of monoclonal IgY antibodies, highlights their advantages over polyclonal IgY antibodies, and discusses their recent applications. Monoclonal recombinant IgY antibodies, in contrast to polyclonal IgY antibodies, offer several benefits. such as derived from a single B-cell clone, monoclonal antibodies exhibit superior specificity, ensuring consistent and reliable results. Furthermore, it explores the suitability of monoclonal IgY antibodies for low- and middle-income countries, considering their cost-effectiveness and accessibility. We also discussed future directions and challenges in using polyclonal IgY and monoclonal IgY antibodies. In conclusion, monoclonal IgY antibodies offer substantial advantages over polyclonal IgY antibodies regarding specificity, scalability, and consistent performance. Their recent applications in diagnostics, therapeutics, and research highlight their versatility.


Chicken egg yolk antibodies (IgY) and monoclonal antibodies: advancements and limitations for immunodiagnosis and immunotherapy applications Chicken egg yolk antibodies (IgY antibodies) and monoclonal antibodies (mAbs) are two types of antibodies used in medical applications. IgY antibodies are cost-effective, stable, and specific, with the advantage of not triggering harmful immune responses. However, they may have limitations in identifying certain target areas and availability. On the other hand, mAbs are highly specific and can detect multiple target areas on antigens, but their production is expensive and may cause immune responses. Despite these drawbacks, both IgY antibodies and mAbs show promise in various applications such as infectious disease diagnosis, cancer treatment, and autoimmune disorders. Ongoing developments in antibody technology are likely to expand their applications in immunology. This review provides an overview of the strengths and limitations of IgY antibodies and mAbs in immunodiagnosis and immunotherapy, as well as their role in pandemic control.

5.
Biomedicines ; 12(5)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38791085

RESUMO

Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-ß1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-ß1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors' expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-ß1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-ß1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-ß1 and indicates independent prognostic significance of high FAS and TGF-ß1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.

6.
Sci Total Environ ; 935: 172877, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38740196

RESUMO

Deep learning techniques have recently found application in biodiversity research. Mayflies (Ephemeroptera), stoneflies (Plecoptera) and caddisflies (Trichoptera), often abbreviated as EPT, are frequently used for freshwater biomonitoring due to their large numbers and sensitivity to environmental changes. However, the morphological identification of EPT species is a challenging but fundamental task. Morphological identification of these freshwater insects is therefore not only extremely time-consuming and costly, but also often leads to misjudgments or generates datasets with low taxonomic resolution. Here, we investigated the application of deep learning to increase the efficiency and taxonomic resolution of biomonitoring programs. Our database contains 90 EPT taxa (genus or species level), with the number of images per category ranging from 21 to 300 (16,650 in total). Upon completion of training, a CNN (Convolutional Neural Network) model was created, capable of automatically classifying these taxa into their appropriate taxonomic categories with an accuracy of 98.7 %. Our model achieved a perfect classification rate of 100 % for 68 of the taxa in our dataset. We achieved noteworthy classification accuracy with morphologically closely related taxa within the training data (e.g., species of the genus Baetis, Hydropsyche, Perla). Gradient-weighted Class Activation Mapping (Grad-CAM) visualized the morphological features responsible for the classification of the treated species in the CNN models. Within Ephemeroptera, the head was the most important feature, while the thorax and abdomen were equally important for the classification of Plecoptera taxa. For the order Trichoptera, the head and thorax were almost equally important. Our database is recognized as the most extensive aquatic insect database, notably distinguished by its wealth of included categories (taxa). Our approach can help solve long-standing challenges in biodiversity research and address pressing issues in monitoring programs by saving time in sample identification.


Assuntos
Aprendizado Profundo , Insetos , Animais , Insetos/anatomia & histologia , Insetos/classificação , Monitoramento Ambiental/métodos , Biodiversidade , Redes Neurais de Computação , Organismos Aquáticos/classificação , Água Doce , Ephemeroptera/anatomia & histologia , Ephemeroptera/classificação
7.
Medicina (Kaunas) ; 60(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38541234

RESUMO

Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels.


Assuntos
Reabsorção Óssea , Inibidores de Hidroximetilglutaril-CoA Redutases , Periodontite , Humanos , Líquido do Sulco Gengival , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Periodontite/tratamento farmacológico , Bolsa Periodontal/terapia
8.
Biomedicines ; 12(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38255201

RESUMO

The aim of this study was to determine the association of basal compartment and superficial markers, comprising CK5/6, CD44, CK20, and the pathological characteristics of upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN). Comparing the expression of the investigated markers in 54 tumors from the BEN region and 73 control UTUC, no significant difference between them was detected. In regression analysis, CK20 expression was not determined with expression of CK5/6, CD44, and the phenotypic characteristics of BEN and control UTUC. Parameters with predictive influence on the expression of CD44 in BEN UTUC included growth pattern (p = 0.010), necrosis (p = 0.019); differentiation (p = 0.001), and lymphovascular invasion (p = 0.021) in control UTUC. Divergent squamous differentiation in BEN tumors (p = 0.026) and stage in control tumors (p = 0.049) had a predictive influence on the expression of CK5/6. This investigation detected a predictive influence of the phenotypic characteristics of UTUC on the expression of basal compartment and superficial markers, with a significant influence of necrosis in BEN tumors (p = 0.006) and differentiation in control UTUC (p = 0.036).

9.
Chirality ; 36(1): e23603, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37410057
10.
Can J Occup Ther ; 91(2): 124-135, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38146163

RESUMO

Background. Public safety personnel (PSP) are frequently exposed to psychological trauma through their work. Evidence shows that worker's compensation claims for work-related psychological injuries are on the rise for PSP. Occupational therapists increasingly provide return to work (RTW) services for this population. Purpose. To explore the therapeutic practices and personal experiences of occupational therapists working with PSP who have work-related psychological injuries. Method. This mixed methods descriptive study included a chart review of available occupational therapy client records from 2016 to 2020 for PSP with work-related psychological injuries from two Ontario companies. Additionally, a web-based self-report survey for Ontario occupational therapists providing RTW services to this same population was available from November 1, 2021 to June 1, 2022. Findings. The chart review included 31 client records and the online survey was completed by 49 Ontario occupational therapists. Therapists commonly provided services in clients' homes, workplaces, and communities, and focused on functional activities. The evidence base drawn on by therapists was not always occupation-based. Barriers to RTW included challenges with interprofessional collaboration, stigma, and the COVID-19 pandemic. Implications. Occupational therapists are commonly working with PSP with work-related psychological injuries and have the opportunity to contribute to the evidence base for occupational approaches to RTW.


Assuntos
Terapia Ocupacional , Retorno ao Trabalho , Humanos , Terapia Ocupacional/organização & administração , Retorno ao Trabalho/psicologia , Ontário , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , COVID-19/reabilitação , Terapeutas Ocupacionais/psicologia
11.
J Clin Med ; 12(20)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37892698

RESUMO

In the current modern era of unhealthy lifestyles, non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and has become a serious global health problem. To date, there is no approved pharmacotherapy for the treatment of NAFLD, and necessary lifestyle changes such as weight loss, diet, and exercise are usually not sufficient to manage this disease. Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing NAFLD and vice versa. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that have recently been approved for two other indications: chronic kidney disease and heart failure in diabetics and non-diabetics. They are also emerging as promising new agents for NAFLD treatment, as they have shown beneficial effects on hepatic inflammation, steatosis, and fibrosis. Studies in animals have reported favorable effects of SGLT2 inhibitors, and studies in patients also found positive effects on body mass index (BMI), insulin resistance, glucose levels, liver enzymes, apoptosis, and transcription factors. There are some theories regarding how SGLT2 inhibitors affect the liver, but the exact mechanism is not yet fully understood. Therefore, biomarkers to evaluate underlying mechanisms of action of SGLT2 inhibitors on the liver have now been scrutinized to assess their potential as a future in-label therapy for NAFLD. In addition, finding suitable non-invasive biomarkers could be helpful in clinical practice for the early detection of NAFLD in patients. This is crucial for a positive disease outcome. The aim of this review is to provide an overview of the most recent findings on the effects of SGLT2 inhibitors on NAFLD biomarkers and the potential of SGLT2 inhibitors to successfully treat NAFLD.

12.
Medicina (Kaunas) ; 59(10)2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37893518

RESUMO

Background and Objectives: This study aimed to examine the efficacy of tapentadol immediate release (IR) and morphine hydrochloride in the treatment of acute postoperative pain after total abdominal hysterectomy, as well as to examine the frequency of opioid-related side effects in observed patients. Materials and Methods: The prospective observational study was conducted over five months, and it included a total number of 100 patients. The two cohorts had different types of postoperative analgesia, and the effects were observed for 24 h postoperatively, by following the pain scores on NRS (Numerical Pain Scale), contentment with analgesia, and opioid-related side effects. Results: Statistical significance was found when assessing pain 24 h after surgery while coughing, where patients in the tapentadol IR group had significantly higher mean pain scores (p < 0.01). The subjective feeling of satisfaction with postoperative analgesia was statistically significant in the tapentadol IR group (p = 0.005). Vertigo appeared significantly more in patients from the morphine group (p = 0.03). Conclusions: Tapentadol IR (immediate release) and morphine hydrochloride are both effective analgesics used in the first 24 h after total transabdominal hysterectomy. Overall satisfaction of patients with analgesia was good. The frequency of side effects was higher in the morphine group, with statistical significance regarding the vertigo.


Assuntos
Analgesia , Analgésicos Opioides , Feminino , Humanos , Tapentadol/uso terapêutico , Analgésicos Opioides/uso terapêutico , Estudos Prospectivos , Fenóis/uso terapêutico , Fenóis/efeitos adversos , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Histerectomia/efeitos adversos , Vertigem/induzido quimicamente , Vertigem/tratamento farmacológico
13.
Biomedicines ; 11(7)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37509493

RESUMO

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

14.
Curr Issues Mol Biol ; 45(6): 4544-4556, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37367037

RESUMO

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, and reduce cardiovascular risk factors. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common liver disease, associated with T2DM, obesity, and metabolic syndrome. GLP-1RAs have been approved for the treatment of T2DM and obesity, but not for NAFLD. Most recent clinical trials have suggested the importance of early pharmacologic intervention with GLP-1RAs in alleviating and limiting NAFLD, as well as highlighting the relative scarcity of in vitro studies on semaglutide, indicating the need for further research. However, extra-hepatic factors contribute to the GLP-1RA results of in vivo studies. Cell culture models of NAFLD can be helpful in eliminating extrahepatic effects on the alleviation of hepatic steatosis, modulation of lipid metabolism pathways, reduction of inflammation, and prevention of the progression of NAFLD to severe hepatic conditions. In this review article, we discuss the role of GLP-1 and GLP-1RA in the treatment of NAFLD using human hepatocyte models.

15.
Curr Issues Mol Biol ; 45(5): 4246-4260, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37232739

RESUMO

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.

16.
Medicina (Kaunas) ; 59(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36676797

RESUMO

A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression's regulation at the post-transcription level through binding to the 3'untranslated regions (UTR), coding sequences, or 5'UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.


Assuntos
Hepatite B , Hepatite C , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Hepatite B/genética , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/genética , Biomarcadores/metabolismo , Hepatite C/genética
17.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203364

RESUMO

Despite its beneficial pharmacological effects in the brain, partly by modulating inositol phosphate multikinase (IPMK) activity, the therapeutic use of quercetin is limited due to its poor solubility, low oral bioavailability, and low permeability through the blood-brain barrier (BBB). We aimed to identify quercetin analogues with improved BBB permeability and preserved binding affinities towards IPMK and to identify the molecular characteristics required for them to permeate the BBB. Binding affinities of quercetin analogues towards IPMK were determined by molecular docking. Principal component analysis (PCA) was applied to identify the molecular descriptors contributing to efficient permeation through the BBB. Among 34 quercetin analogues, 19 compounds were found to form more stable complexes with IPMK, and the vast majority were found to be more lipophilic than quercetin. Using two distinct in silico techniques, insufficient BBB permeation was determined for all quercetin analogues. However, using the PCA method, the descriptors related to intrinsic solubility and lipophilicity (logP) were identified as mainly responsible for clustering four quercetin analogues (trihydroxyflavones) with the highest BBB permeability. The application of PCA revealed that quercetin analogues could be classified with respect to their structural characteristics, which may be utilized in further analogue syntheses and lead optimization of BBB-penetrating IPMK modulators as neuroprotective agents.


Assuntos
Barreira Hematoencefálica , Quercetina , Análise de Componente Principal , Quercetina/farmacologia , Simulação de Acoplamento Molecular , Encéfalo , Fosfatos de Inositol
18.
Pathogens ; 13(1)2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38251345

RESUMO

Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal.

19.
Biomedicines ; 10(12)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36552021

RESUMO

Although we are lately witnessing major improvements in breast cancer treatment and patient outcomes, there is still a significant proportion of patients not receiving efficient therapy. More precisely, patients with triple-negative breast cancer or any type of metastatic disease. Currently available prognostic and therapeutic biomarkers are not always applicable and oftentimes lack precision. The science of glycans is a relatively new scientific approach to better characterize malignant transformation and tumor progression. In this review, we summarize the most important information about glycosylation characteristics in breast cancer cells and how different glycoproteins and enzymes involved in glycosylation could serve as more precise biomarkers, as well as new therapeutic targets.

20.
J Clin Transl Hepatol ; 10(6): 1186-1193, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36381097

RESUMO

Interleukin (IL) 1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver. Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage, the release of inflammatory cytokines and disturbances in gut microbiota. IL1 cytokines and receptors can have pro- or anti-inflammatory roles, even dual functionalities conditioned by the microenvironment. Developing novel therapeutic strategies to block the IL1/IL1R signaling pathways seems like a reasonable option. This mode of action is now exploited by anakinra and canakinumab, which are used to treat different inflammatory illnesses, and studies in liver diseases are on the way. In this mini review, we have focused on the IL1 superfamily members, given their crucial role in liver inflammation diseases, specifically discussing their potential role in developing new treatment strategies.

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