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1.
J Vet Res ; 68(3): 409-417, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39318512

RESUMO

Introduction: Chokeberry pomace, rich in polyphenolic compounds, holds potential to be a valuable feed additive for enhancing the antioxidative capacity and overall quality of milk. This study explores the impact of dietary inclusion of chokeberry pomace on oxidative stress parameters and other milk quality parameters in high-producing dairy goats. Material and Methods: Twenty-seven goats were allocated into three groups: a control group provided standard feed and two experimental groups provided feed supplemented with 15 g or 30 g of chokeberry pomace per kilogram. Milk samples were analysed for physicochemical traits, a range of enzyme activities and antioxidant properties. Results: Supplementation with chokeberry pomace significantly reduced milk fat content, enhanced antioxidative properties and increased most of the quantified enzyme activities. Total polyphenol content and reduced glutathione levels were significantly higher in the supplemented groups, correlating with improved antioxidative potential of the milk. Conclusion: Chokeberry pomace in goat diets enhances milk's antioxidative properties and upregulates its enzymatic activity profile, suggesting a potential strategy to improve the nutritional quality and health benefits of goat milk. The study underscores the utility of chokeberry pomace as a feed additive that might not only benefit animal health but also contribute to enhanced milk quality.

2.
Curr Issues Mol Biol ; 46(8): 8301-8319, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39194707

RESUMO

The accurate identification of the primary tumor origin in metastatic cancer cases is crucial for guiding treatment decisions and improving patient outcomes. Copy number alterations (CNAs) and copy number variation (CNV) have emerged as valuable genomic markers for predicting the origin of metastases. However, current models that predict cancer type based on CNV or CNA suffer from low AUC values. To address this challenge, we employed a cutting-edge neural network approach utilizing a dataset comprising CNA profiles from twenty different cancer types. We developed two workflows: the first evaluated the performance of two deep neural networks-one ReLU-based and the other a 2D convolutional network. In the second workflow, we stratified cancer types based on anatomical and physiological classifications, constructing shallow neural networks to differentiate between cancer types within the same cluster. Both approaches demonstrated high AUC values, with deep neural networks achieving a precision of 60%, suggesting a mathematical relationship between CNV type, location, and cancer type. Our findings highlight the potential of using CNA/CNV to aid pathologists in accurately identifying cancer origins with accessible clinical tests.

3.
Front Pharmacol ; 15: 1399719, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135805

RESUMO

Diabetes mellitus (DM) is a prevalent metabolic disease. The clinical impact of sustained hyperglycemia on ligament healing has not been well characterized. Diabetes is a known cause of macro-, microvascular, and diabetic ulcer healing difficulties among tissues. Therefore, we aimed to investigate the healing potential occurring in injured and healthy ligaments among diabetic and healthy individuals using a rat model. We hypothesize that DM may contribute to altering the knee medial collateral ligament (MCL), thus its morphology, biochemical fitness, and functionality. The study cohort consisted of 40 rats. The animals were randomized into four equal groups. Groups I and II (20 rats) received saline subcutaneously and served as controls. Groups III and IV (20 rats) were injected with a single dose of streptozotocin (STZ). All animals underwent surgery to cut the left tibial collateral ligament in the hind limb and suture it. The access site was sutured to create inflammation and study the regenerative capacities of animals with normal carbohydrate metabolism and pharmacologically induced diabetes. Each animal then underwent sham surgery to access and suture the right tibial collateral ligament in the hind limb without ligament intervention. After the animals had undergone surgeries, groups II and IV were given melatonin supplementation for 4 weeks. Rats with DM presented with more fibrosis and calcification of the MCL and decreased healing potential. Treatment with melatonin in diabetic rats mitigated alterations and improved the antioxidant status of ligaments from the diabetic group.

4.
Int J Surg ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652180

RESUMO

As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.

5.
Front Med (Lausanne) ; 10: 1138051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497278

RESUMO

Objectives: Continuous non-invasive monitoring of blood pressure is one of the main factors in ensuring the safety of the patient's condition in anesthesiology, intensive care, surgery, and other areas of medicine. The purpose of this work was to analyze the current patent situation and identify directions and trends in the application of non-invasive medical sensors for continuous blood pressure monitoring, with a focus on clinical experience in critical care and validation thereof. Materials and methods: The research results reflect data collected up to September 30, 2022. Patent databases, Google Scholar, the Lens database, Pubmed, Scopus databases were used to search for patent and clinical information. Results: An analysis of the patent landscape indicates a significant increase in interest in the development of non-invasive devices for continuous blood pressure monitoring and their implementation in medical practice, especially in the last 10 years. The key players in the intellectual property market are the following companies: Cnsystems Medizintechnik; Sotera Wireless INC; Tensys Medical INC; Healthstats Int Pte LTD; Edwards Lifesciences Corp, among others. Systematization of data from validation and clinical studies in critical care practice on patients with various pathological conditions and ages, including children and newborns, revealed that a number of non-invasive medical sensor technologies are quite accurate and comparable to the "gold standard" continuous invasive blood pressure monitoring. They are approved by the FDA for medical applications and certified according to ISO 81060-2, ISO 81060-3, and ISO/TS 81060-5. Unregistered and uncertified medical sensors require further clinical trials. Conclusion: Non-invasive medical sensors for continuous blood pressure monitoring do not replace, but complement, existing methods of regular blood pressure measurement, and it is expected to see more of these technologies broadly implemented in the practice in the near future.

6.
Digit Health ; 9: 20552076231179053, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37312949

RESUMO

Objective: This study provided a content analysis of English and Chinese YouTube videos related to dental radiation safety. Method: The search string, entered in English and Chinese respectively, was: (dental x-ray safe). The searches were performed and exported with Apify YouTube scraper. By screening the resultant videos and their related videos (as recommended by YouTube), a total of 89 videos were screened. Finally, 45 videos (36 English and nine Chinese) were included and analyzed. The specific information regarding dental radiation was evaluated. The Patient Education Material Assessment Tool for Audiovisual Materials was used to assess understandability and actionability. Results: There was no significant difference between the English and Chinese videos in terms of view count, like count, comment count, and video duration. Half of the videos explicitly reassured the audience that dental x-rays are safe. Two of the English videos specifically stated that dental x-rays do not cause cancers. Numerous analogies were made in regard to radiation dose, such as equivalence to taking a flight or eating some bananas. About 41.7% of the English videos and 33.3% of the Chinese videos mentioned that patients could be further protected from scatter radiation by wearing a lead apron and thyroid collar. Videos had a good understandability score (91.3) but a poor actionability score (0). Conclusions: Some of the analogies and the claimed radiation dose were questionable. One Chinese video even wrongly stated that dental x-rays are nonionizing radiation. The videos generally did not mention their information sources or the underlying radiation protection principles.

7.
Int J Mol Sci ; 24(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37298715

RESUMO

Type 2 diabetes (T2D) accounts for a global health problem. It is a complex disease as a result of the combination of environmental as well as genetic factors. Morbidity is still increasing across the world. One of the possibilities for the prevention and mitigation of the negative consequences of type 2 diabetes is a nutritional diet rich in bioactive compounds such as polyphenols. This review is focused on cyanidin-3-O-glucosidase (C3G), which belongs to the anthocyanins subclass, and its anti-diabetic properties. There are numerous pieces of evidence that C3G exerts positive effects on diabetic parameters, including in vitro and in vivo studies. It is involved in alleviating inflammation, reducing blood glucose, controlling postprandial hyperglycemia, and gene expression related to the development of T2D. C3G is one of the beneficial polyphenolic compounds that may help to overcome the public health problems associated with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Glucosídeos , Nutrigenômica
8.
Front Immunol ; 14: 1147991, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033914

RESUMO

Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.


Assuntos
COVID-19 , Canabidiol , Humanos , SARS-CoV-2 , Canabidiol/uso terapêutico , Tratamento Farmacológico da COVID-19 , Anti-Inflamatórios/uso terapêutico , Imunossupressores
10.
Antioxidants (Basel) ; 12(2)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36829966

RESUMO

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols-natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment.

11.
Pharmacol Res ; 186: 106505, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36243332

RESUMO

Chlorogenic acid (CA), also known as 5-O-caffeoylquinic acid, is a dietary phenolic acid produced by various plant species. CA, is the most ubiquitous compound among the phenolic acid group, is also present in tea and green coffee extracts. Its consumption reduces the risk of numerous diseases as validated by preclinical and clinical studies. CA possesses a wide range of pharmacological properties, such as hepatoprotective, antimicrobial, immunomodulatory, antioxidant, antidiabetic, and anticancer activities. It has been extensively used in the food, chemical, medicine, and health care industries. Available reports revealed that CA can exert anticancer activity by inhibiting the cell cycle, triggering apoptosis, and suppressing the proliferation of cancer cells. It upregulates the expression of nuclear factor of activated T cells 2 (NFATC2) and NFATC3 genes involved in immune pathway and downregulates B cell-specific moloney murine leukemia virus integration site 1 protein and SRY-box transcription factor 2 gene expression to facilitate tumor cell destruction. It promotes intracellular DNA impairment and topoisomerase I- and topoisomerase-II-DNA complex formation that perform a key function in apoptosis. In addition, CA has been documented to be an effective natural anticancer drug and was approved by the China Food and Drug Administration. Several previously published reports have provided fragmented summary of various anticancer activities of CA. Therefore, this review aims to deliver up-to-date and comprehensive assessment about the natural sources of CA, its bioavailability, metabolism, and anticancer property with an emphasis on the molecular mechanisms associated with several signaling pathways in tumor cells.


Assuntos
Ácido Clorogênico , Neoplasias , Estados Unidos , Camundongos , Animais , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Hidroxibenzoatos/farmacologia , Antioxidantes/farmacologia , Apoptose , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle
12.
Cureus ; 14(9): e28767, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36211105

RESUMO

Background The easy accessibility of smartphones and internet connections enables people to stay virtually connected to communities via social media. However, social media is also being explored for health care education and dissemination of health-related information. Twitter (Twitter, Inc., San Francisco, California) is one of the popular social media used for spreading health-related information. Twitter enables users to create polls to get opinions from their users. The Twitter poll is a less-explored avenue for health surveys. Objective In this pilot study, we aimed to explore the feasibility of conducting a questionnaire-based health survey (on the preference of different systems of medicine for the treatment of various health problems) as a Twitter poll. Methods This observational study was conducted on Twitter for five consecutive days starting from May 31, 2021. We posted five Twitter polls, one poll each day, for five days in a #INPST unique Twitter campaign. Preferences on the use of modern medicine, traditional medicine, a combination of these two systems, and self-medication were collected on five health conditions. We collected the data from the landing poll page and Tweet Analytics (insight about the engagement of tweets provided free by Twitter). The Chi-square test, binomial test, and one-way Analysis of Variance were used to compare data, and Spearman's rank correlation coefficient was used to find a correlation between categorical variables. Results We had a mean 4358.6±590.3 poll reach with the engagement of 108.2±36.87 Twitter users and 67.6±28.06 votes. Most of the responses were received on the first day of posting the poll. The participation then gradually decreased. Modern medicine was the first choice for emergency medical care (85.1%, P <0.0001), treatment of cancer (43.6%, P <0.0001), and sexual disorder or transmitted diseases (48.9%, P <0.0001). Traditional medicine was the first choice (37.5%, P = 0.63) for the treatment of common illnesses, and a combination of modern and traditional medicine was the first choice (37.5%, P = 0.01) for the treatment of chronic diseases. Conclusion A medical survey with short questions with a maximum of four response options can be conducted on Twitter. Survey results can be obtained without any third-party analytic service. The response rate is highest on the first day and participation may decrease when multiple polls are posted within a Twitter campaign. Preference for systems of medicine found in this study can be used for designing large-scale surveys in the future.

13.
Int J Mol Sci ; 23(18)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36142387

RESUMO

The study aimed to evaluate the effect of dried apple pomace (DAP) as a feed additive on the enzymatic activity and non-enzymatic compounds belonging to the antioxidant system in cattle rumen fluid. The experiment included 4 Polish Holstein−Friesian cannulated dairy cows and lasted 52 days. The control group was fed with the standard diet, while in the experimental group, 6% of the feedstuff was replaced by dried apple pomace. After the feeding period, ruminal fluid was collected. The spectrophotometric technique for the activity of lysosomal enzymes, the content of vitamin C, polyphenols, and the potential to scavenge the free DPPH radical was used. The enzyme immunoassay tests (ELISA) were used to establish the activity of antioxidants enzymes and MDA. Among the rumen aminopeptidases, a significant reduction (p < 0.01) from 164.00 to 142.00 was observed for leucyl-aminopeptidase. The activity of glycosidases was decreased for HEX (from 231.00 to 194.00) and ß-Glu (from 1294.00 to 1136.00), while a significant statistically increase was noticed for BGRD (from 31.10 to 42.40), α-Glu (from 245.00 to 327.00), and MAN (from 29.70 to 36.70). Furthermore, the activity of catalase and GSH (p < 0.01) was inhibited. In turn, the level of vitamin C (from 22.90 to 24.10) and MDA (from 0.36 to 0.45) was statistically higher (p < 0.01). The most positive correlations were observed between AlaAP and LeuAP (r = 0.897) in the aminopeptidases group and between ß-Gal and MAN (r = 0.880) in the glycosidases group. Furthermore, one of the most significant correlations were perceived between SOD and AlaAP (r = 0.505) and AcP (r = 0.450). The most negative correlation was noticed between α-Gal and DPPH (r = −0.533) based on these observations. Apple pomace as a feed additive has an influence on lysosomal degradation processes and modifies oxidation−reduction potential in the rumen fluid. Polyphenols and other low-weight antioxidant compounds are sufficient to maintain redox balance in the rumen.


Assuntos
Malus , Rúmen , Aminopeptidases/metabolismo , Ração Animal/análise , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Catalase/metabolismo , Bovinos , Dieta/veterinária , Feminino , Fermentação , Glicosídeo Hidrolases/metabolismo , Humanos , Lactação , Malus/metabolismo , Leite/química , Polifenóis/farmacologia , Rúmen/química , Superóxido Dismutase/metabolismo
14.
Pharmaceuticals (Basel) ; 15(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36015173

RESUMO

The modern healthcare system is directly related to the development of digital health tools and solutions. Pills with digital sensors represent a highly innovative class of new pharmaceuticals. The aim of this work was to analyze the patent landscape and to systematize the main trends in patent protection of digital pills with ingestible sensors worldwide; accordingly, to identify the patenting leaders as well as the main prevailing areas of therapy for patent protection, and the future perspectives in the field. In July 2022, a search was conducted using Internet databases, such as the EPO, USPTO, FDA and the Lens database. The patent landscape analysis shows an increase in the number of patents related to digital pills with ingestible sensors for mobile clinical monitoring, smart drug delivery, and endoscopy diagnostics. The leaders in the number of patents issued are the United States, the European Patent Office, Canada, Australia, and China. The following main areas of patenting digital pills with ingestible sensors were identified: treatment in the field of mental health; HIV/AIDS; pain control; cardiovascular diseases; diabetes; gastroenterology (including hepatitis C); oncology; tuberculosis; and transplantology. The development of scientific and practical approaches towards the implementation of effective and safe digital pills will improve treatment outcomes, increase compliance, reduce hospital stays, provide mobile clinical monitoring, have a positive impact on treatment costs and will contribute to increased patient safety.

16.
Front Public Health ; 10: 856571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844878

RESUMO

Background: Artificial intelligence (AI) has the potential to reshape medical practice and the delivery of healthcare. Online discussions surrounding AI's utility in these domains are increasingly emerging, likely due to considerable interest from healthcare practitioners, medical technology developers, and other relevant stakeholders. However, many practitioners and medical students report limited understanding and familiarity with AI. Objective: To promote research, events, and resources at the intersection of AI and medicine for the online medical community, we created a Twitter-based campaign using the hashtag #MedTwitterAI. Methods: In the present study, we analyze the use of #MedTwitterAI by tracking tweets containing this hashtag posted from 26th March, 2019 to 26th March, 2021, using the Symplur Signals hashtag analytics tool. The full text of all #MedTwitterAI tweets was also extracted and subjected to a natural language processing analysis. Results: Over this time period, we identified 7,441 tweets containing #MedTwitterAI, posted by 1,519 unique Twitter users which generated 59,455,569 impressions. The most common identifiable locations for users including this hashtag in tweets were the United States (378/1,519), the United Kingdom (80/1,519), Canada (65/1,519), India (46/1,519), Spain (29/1,519), France (24/1,519), Italy (16/1,519), Australia (16/1,519), Germany (16/1,519), and Brazil (15/1,519). Tweets were frequently enhanced with links (80.2%), mentions of other accounts (93.9%), and photos (56.6%). The five most abundant single words were AI (artificial intelligence), patients, medicine, data, and learning. Sentiment analysis revealed an overall majority of positive single word sentiments (e.g., intelligence, improve) with 230 positive and 172 negative sentiments with a total of 658 and 342 mentions of all positive and negative sentiments, respectively. Most frequently mentioned negative sentiments were cancer, risk, and bias. Most common bigrams identified by Markov chain depiction were related to analytical methods (e.g., label-free detection) and medical conditions/biological processes (e.g., rare circulating tumor cells). Conclusion: These results demonstrate the generated considerable interest of using #MedTwitterAI for promoting relevant content and engaging a broad and geographically diverse audience. The use of hashtags in Twitter-based campaigns can be an effective tool to raise awareness of interdisciplinary fields and enable knowledge-sharing on a global scale.


Assuntos
Mídias Sociais , Inteligência Artificial , Brasil , Alemanha , Humanos , Espanha , Estados Unidos
17.
J Patient Saf ; 18(7): e1116-e1123, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35617635

RESUMO

OBJECTIVE: The aim of the study was to quantitatively analyze the scientific literature landscape covering legal regulations of patient safety. METHODS: This retrospective bibliometric analysis queried Web of Science database to identify relevant publications. The identified scientific literature was quantitatively evaluated to reveal prevailing study themes, contributing journals, countries, institutions, and authors, as well as citation patterns. RESULTS: The identified 1295 publications had a mean of 13.8 citations per publication and an h-index of 57. Approximately 78.8% of them were published since 2010, with the United States being the top contributor and having the greatest publication growth. A total of 79.2% (n = 1025) of the publications were original articles, and 12.5% (n = 162) were reviews. The top authors (by number of publications published on the topic) were based in the United States and Spain and formed 3 collaboration clusters. The top institutions by number of published articles were mainly based in the United States and United Kingdom, with Harvard University being on top. Internal medicine, surgery, and nursing were the most recurring clinical disciplines. Among 4 distinct approaches to improve patient safety, reforms of the liability system (n = 91) were most frequently covered, followed by new forms of regulation (n = 73), increasing transparency (n = 67), and financial incentives (n = 38). CONCLUSIONS: Approximately 78.8% of the publications on patient safety and its legal implications were published since 2010, and the United States was the top contributor. Approximately 79.2% of the publications were original articles, whereas 12.5% were reviews. Healthcare sciences services was the most recurring journal category, with internal medicine, surgery, and nursing being the most recurring clinical disciplines. Key relevant laws around the globe were identified from the literature set, with some examples highlighted from the United States, Germany, Italy, France, Sweden, Poland, and Indonesia. Our findings highlight the evolving nature and the diversity of legislative regulations at international scale and underline the importance of healthcare workers to be aware of the development and latest advancement in this field and to understand that different requirements are established in different jurisdictions so as to safeguard the necessary standards of patient safety.


Assuntos
Bibliometria , Segurança do Paciente , Bases de Dados Factuais , Alemanha , Humanos , Estudos Retrospectivos , Estados Unidos
18.
Amino Acids ; 54(6): 897-910, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35562605

RESUMO

The Alzheimer's disease leads to neurodegenerative processes and affecting negatively million people worldwide. The treatment of the disease is still difficult and incomplete in practice. Galanthamine is one of the most commonly used drugs against the illness. The main aim of this work is design and synthesis of new derivatives of galanthamine comprising peptide moiety as well as study of their ß-secretase inhibitory activity and the anti-aggregating effect. All new derivatives of galanthamine containing analogues of Leu-Val-Phe-Phe (Aß17-Aß20) were synthesized in solution using fragment and consecutive condensation approaches. The new derivatives were characterized by melting points, NMR, and HPLC/MS. They were tested in vitro for ß-secretase inhibition activity by means of fluorescent method and were investigated in vitro for anti-aggregation activity on sheep platelet-rich plasma. Although the new compounds do not contain a structural element responsible for the ß-secretase inhibition, five of them show high or good ß-secretase inhibitory activity between 19.98 and 51.19% with IC50 between 1.95 and 5.26 nM. Four of the new molecules were able to inhibit platelet aggregation between 55.0 and 90.0% with IC50 between 0.69 and 1.36 µM. Four of the compounds were able to inhibit platelet aggregation and two of them have high anti-aggregating effects.


Assuntos
Doença de Alzheimer , Galantamina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Animais , Galantamina/química , Galantamina/farmacologia , Galantamina/uso terapêutico , Humanos , Peptídeos/química , Ovinos
19.
J Pers Med ; 12(3)2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35330454

RESUMO

Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusions: The study revealed differences in the mutational landscape of lung cancer histotypes.

20.
Semin Cancer Biol ; 86(Pt 3): 706-731, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34062265

RESUMO

Microbial polysaccharides (MPs) offer immense diversity in structural and functional properties. They are extensively used in advance biomedical science owing to their superior biodegradability, hemocompatibility, and capability to imitate the natural extracellular matrix microenvironment. Ease in tailoring, inherent bio-activity, distinct mucoadhesiveness, ability to absorb hydrophobic drugs, and plentiful availability of MPs make them prolific green biomaterials to overcome the significant constraints of cancer chemotherapeutics. Many studies have demonstrated their application to obstruct tumor development and extend survival through immune activation, apoptosis induction, and cell cycle arrest by MPs. Synoptic investigations of MPs are compulsory to decode applied basics in recent inclinations towards cancer regimens. The current review focuses on the anticancer properties of commercially available and newly explored MPs, and outlines their direct and indirect mode of action. The review also highlights cutting-edge MPs-based drug delivery systems to augment the specificity and efficiency of available chemotherapeutics, as well as their emerging role in theranostics.


Assuntos
Materiais Biocompatíveis , Neoplasias , Humanos , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/química , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Polissacarídeos/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Microambiente Tumoral
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