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1.
Artigo em Inglês | MEDLINE | ID: mdl-38953771

RESUMO

OBJECTIVES: One stage functional jaw reconstruction is defined as the resection and reconstruction of segmental defects in conjunction with the placement of dental implants in an ideal prosthetic position and loaded with a provisional restoration, during one surgical procedure. The aim of the study is to describe clinical outcomes of patients who underwent one stage functional jaw reconstruction. METHODS: Patients who underwent one-stage functional jaw reconstruction, from January 2013 to March 2016 were recalled in 2022 and 2023. Planning and execution for the reconstruction utilized either analogue or digital techniques. Outcome parameters recorded were treatment-related outcomes at patient level, implant-related outcomes and patient-reported outcome measures. RESULTS: Eighteen patients underwent one-stage jaw reconstruction with a total of 57 implants. Four patients had maxillary and 14 had mandibular reconstructions. Ten patients underwent postoperative radiotherapy. Ten patients were planned using analogue and eight by digital planning. Three patients had partial flap necrosis, three patients had plate fractures, implant loss was seen in one patient and four patients died during the period. A functional prosthesis was provided in 16 out of the 18 patients. CONCLUSION: One-stage functional jaw reconstruction is a predictable method for providing rehabilitation with successful outcomes at 7-11 years. However, caution should be exercised when the treatment modality is carried out in patients with malignant pathologies who have undergone radiotherapy.

2.
ACS Appl Bio Mater ; 7(7): 4417-4426, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875229

RESUMO

In the present study, we have engineered a molecular logic gate system employing both Fe2+ ions and cholesterol as bioanalytes for innovative detection strategies. We utilized a green-synthesis method employing the mango leaves extract to create fluorescent graphene quantum dots termed "mGQDs". Through techniques like HR-TEM, i.e., high-resolution transmission electron microscopy, Raman spectroscopy, and XPS, i.e., X-ray photoelectron spectroscopy, the successful formation of mGQDs was confirmed. The photoluminescence (PL) characteristics of mGQDs were investigated for potential applications in metal ion detection, specifically Fe2+ traces in water, by using fluorescence techniques. Under 425 nm excitation, mGQDs exhibited emission bands at 495 and 677 nm in their PL spectrum. Fe2+-induced notable quenching of mGQDs' PL intensity decreased by 97% with 2.5 µM Fe2+ ions; however, adding 20 mM cholesterol resulted in a 92% recovery. Detection limits were established through a linear Stern-Volmer (S-V) plot at room temperature, yielding values of 4.07 µM for Fe2+ ions and 1.8 mM for cholesterol. Moreover, mGQDs demonstrated biocompatibility, aqueous solubility, and nontoxicity, facilitating the creation of a rapid nonenzymatic cholesterol detection method. Selectivity and detection studies underscored mGQDs' reliability in cholesterol level monitoring. Additionally, a molecular logic gate system employing Fe2+ metal ions and cholesterol as a bioanalyte was established for detection purposes. Overall, this research introduces an ecofriendly approach to craft mGQDs and highlights their effectiveness in detecting metal ions and cholesterol, suggesting their potential as versatile nanomaterials for diverse analytical and biomedical applications.


Assuntos
Materiais Biocompatíveis , Colesterol , Grafite , Ferro , Mangifera , Teste de Materiais , Tamanho da Partícula , Folhas de Planta , Pontos Quânticos , Pontos Quânticos/química , Grafite/química , Colesterol/análise , Colesterol/química , Folhas de Planta/química , Mangifera/química , Ferro/química , Ferro/análise , Materiais Biocompatíveis/química , Íons/química , Íons/análise , Humanos
3.
Chemosphere ; 362: 142584, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866332

RESUMO

The safety and health of aquatic organisms and humans are threatened by the increasing presence of pollutants in the environment. Endocrine disrupting chemicals are common pollutants which affect the function of endocrine and causes adverse effects on human health. These chemicals can disrupt metabolic processes by interacting with hormone receptors upon consumptions by humans or aquatic species. Several studies have reported the presence of endocrine disrupting chemicals in waterbodies, food, air and soil. These chemicals are associated with increasing occurrence of obesity, metabolic disorders, reproductive abnormalities, autism, cancer, epigenetic variation and cardiovascular risk. Conventional treatment processes are expensive, not environment friendly and unable to achieve complete removal of these harmful chemicals. In recent years, biochar from different sources has gained a considerable interest due to their adsorption efficiency with porous structure and large surface areas. biochar derived from lignocellulosic biomass are widely used as sustainable catalysts in soil remediation, carbon sequestration, removal of organic and inorganic pollutants and wastewater treatment. This review conceptualizes the production techniques of biochar from lignocellulosic biomass and explores the functionalization and interaction of biochar with endocrine-disrupting chemicals. This review also identifies the further needs of research. Overall, the environmental and health risks of endocrine-disrupting chemicals can be dealt with by biochar produced from lignocellulosic biomass as a sustainable and prominent approach.

4.
Discov Nano ; 19(1): 107, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913270

RESUMO

The imperative development of a cutting-edge environmental gas sensor is essential to proficiently monitor and detect hazardous gases, ensuring comprehensive safety and awareness. Nanostructures developed from metal oxides are emerging as promising candidates for achieving superior performance in gas sensors. NO2 is one of the toxic gases that affects people as well as the environment so its detection is crucial. The present study investigates the gas sensing capability of copper oxide-based sensor for 5 ppm of NO2 gas at 100 °C. The sensing material was synthesized using a facile precipitation method and characterized by XRD, FE-SEM, UV-visible spectroscopy, photoluminescence spectroscopy, XPS and BET techniques. The developed material shows a response equal to 67.1% at optimal temperature towards 5 ppm NO2 gas. The sensor demonstrated an impressive detection limit of 300 ppb, along with a commendable percentage response of 5.2%. Under optimized conditions, the synthesized material demonstrated its high selectivity, as evidenced by the highest percentage response recorded for NO2 gas among NO2, NH3, CO, CO2 and H2S.

5.
J Oral Biol Craniofac Res ; 14(4): 455-460, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38868459

RESUMO

Introduction: Orthognathic surgery results in the positional change of the maxilla and mandible that may affect speech. The present study evaluated the effect of combined maxillary advancement and mandibular setback surgery on articulation proficiency and speech intelligibility in patients with non-syndromic skeletal Class III malocclusion. Methods: In this prospective study, twenty-five patients with skeletal class III malocclusion and consecutively treated with Lefort-1 maxillary advancement and mandibular setback (BSSO) orthognathic surgery were included in this study. The speech sample was recorded with a digital audio tape recorder one day before surgery and at 3, 6, 9, 12 and 18 months after surgery. Three qualified and experienced speech and language pathologists evaluated articulation errors and intelligibility of speech samples. Repeated One-way analysis of variance was used to compare articulation proficiency and speech intelligibility at different time intervals. Results: The substitution, omission, distortion and addition errors showed no significant changes at 3 months and 6 months. The total articulation errors decreased to zero at 9 months and no significant increase was observed till 18 months (P < 0.05). Speech intelligibility showed statistically non-significant improvement at any time interval. Cephalometric skeletal parameters SNA and N l A°. were significantly correlated with addition and total articulation errors at 18 months follow up. Conclusions: The ortho-surgical treatment improves speech (decreases. articulation errors) in most of the patients usually 6-9 months post-surgery. Speech intelligibility is not affected by bimaxillary orthognathic surgery in skeletal class III patients. The articulation errors were correlated to changes in position of maxilla.

7.
J Maxillofac Oral Surg ; 23(3): 639-643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911398

RESUMO

This 10-year follow-up report describes the interdisciplinary comprehensive management of a patient with aneurysmal bone cyst of the maxilla in a 24-year-old patient. The treatment included resection and primary reconstruction with vascularized deep circumflex iliac artery-based composite free flap, implant placement, and peri-implant soft tissue management using denture-guided epithelial regeneration with interim dentures. Definitive management was done using implant-supported cast partial dentures, and the patient followed up for 10 years.

8.
J Pharm Bioallied Sci ; 16(Suppl 2): S1161-S1163, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882739

RESUMO

Wound healing refers to the replacement of destroyed or damaged tissue of a living organism by newly produced tissue, and the time taken is known as wound regeneration time. Wound care is a major challenging biomedical field due to the delayed healing process or delayed wound regeneration time. The factors responsible for delayed wound healing are poor oxygen flow, less exposure to moisture, diseases such as diabetes and cancer, etc., Wound dressings that are formulated from biopolymers such as chitosan, chitin, and cellulose have properties such as biocompatibility (compatible with living systems and does not cause any immunological rejection), biodegradable, nontoxic with minimal side effects, anti-microbial, anti-inflammatory properties. Chitosan is obtained from scales of fish and shrimp. It contains highly reactive amine groups and sodium alginate, which is a polysaccharide produced from seaweed and bacteria and is biocompatible with living systems and biodegradable polysaccharides. This study is based on the development of sodium alginate crosslinked hydrogel and testing the properties of hydrogel with amoxycillin drug and water release property of the drug.

9.
J Pharm Bioallied Sci ; 16(Suppl 2): S1195-S1197, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882750

RESUMO

Dextrose cross-linked glutaraldehyde hydrogels are effective and promising drug delivery candidates. The addition of chitosan with dextrose resulted in the polymerization of material which resulted in the production of a gel-like structure that was highly viscous and had gelling properties. A swelling and absorption assay was conducted on the hydrogel. The dextrose cross-linked hydrogel has a higher absorption potential for distilled water followed by PBS and the least absorption was observed in the ethanol. Dextrose cross-linked hydrogel favors solubility in distilled water as compared to other solvents. The amoxicillin release by the dextrose cross-linked hydrogel was then tested. The result from drug release demonstrates that the dextrose cross-linked hydrogel released more than 55% of the amoxicillin in 2 hours and the remaining portion of the drug remaining. Therefore, it has a slow drug-release property, and it can be used for further wound-healing studies.

10.
J Pharm Bioallied Sci ; 16(Suppl 2): S1204-S1206, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882755

RESUMO

Delayed wound healing is one of the most common problems associated with diabetic patients. There are several factors associated with delayed wound healing. It has been observed that if not cured the wound healing takes a long time. This is the reason that researchers are engaged in developing sustainable, biodegradable, biocompatible, and effective wound-healing dressings. However, it has been observed that the traditional wound-healing bandages have drawbacks such as allergies and less efficiency in the absorption of wound exudate. To fill the gap, hydrogels have been developed recently which have higher absorption capacity. In addition, they pose slow drug release properties. Therefore, the present study was conducted to prepare an effective and promising hydrogel that has high drug absorption and release properties.

11.
J Pharm Bioallied Sci ; 16(Suppl 2): S1198-S1200, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882769

RESUMO

In this study, we synthesized and characterized a novel starch glutaraldehyde cross-linked hydrogel for drug release. The hydrogel exhibited excellent properties such as absorption capacity and drug release. By optimizing the cross-linking reaction using varying concentrations of glutaraldehyde and reaction time, we obtained a hydrogel with a three-dimensional network structure, superior swelling properties, and mechanical strength. The results revealed doxycycline sustained and controlled drug release over a prolonged period, which could be adjusted by altering the cross-linking density of the hydrogel. Overall, the starch glutaraldehyde cross-linked hydrogel shows great promise as a drug delivery system with controlled release properties, applicable in pharmaceuticals and tissue engineering.

12.
J Pharm Bioallied Sci ; 16(Suppl 2): S1201-S1203, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882858

RESUMO

Three-dimensional polymeric networks called hydrogels have drawn a lot of interest in a variety of biomedical applications because of their distinctive qualities, like high water content and biocompatibility. Hydrogels can be strengthened mechanically and become more stable via cross-linking. In this study, we described the synthesis and characterization of a cross-linked hydrogel made of polyethylene glycol (PEG) capable of absorbing drug. The hydrogel was created by using a polymerization procedure to cross-link PEG chains. In order to allay this worry, we added particular functional groups to the hydrogel matrix that had a strong affinity for glutaraldehyde. These functional groups made it easier for excess glutaraldehyde to be absorbed and sequestered inside the hydrogel, lowering its cytotoxic potential. After incubation with the hydrogel, the residual glutaraldehyde concentration in solution was measured in order to assess the glutaraldehyde absorption potential.

13.
Cureus ; 16(5): e60412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38883116

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) patients experience disproportionately worse mental health, with implications for adherence, outcomes, and families. Comprehensive assessments of comorbid depression/anxiety and related factors remain limited. OBJECTIVE: This study aimed to assess the prevalence, predictors, and qualitative experiences of depression and anxiety in MDR-TB patients and household contacts. METHODS: A sequential explanatory mixed methods study was conducted in Gujarat, India, with 403 smear-positive MDR-TB patients and 403 contacts. The quantitative phase administered structured questionnaires on sociodemographic factors, clinical history, depression/anxiety symptoms, and psychosocial stressors (like stigma and social support). Logistic regression models were used. The qualitative phase included in-depth interviews with 30 purposively sampled patients for thematic content analysis. Results were integrated to contextualize quantitative findings. RESULTS: High rates of depression (37.5%, n = 151) and anxiety (45.2%, n = 182) were documented among the MDR-TB patients, significantly greater than household contacts (20.1%, n = 81 and 25.1%, n = 101, respectively). For depression, older age (adjusted odds ratio (AOR) 2.03, 95% CI 1.01-4.05), female gender (AOR 2.5, 95% CI 1.1-6.0), divorced/widowed status (AOR 3.8, 95% CI 1.1-8.0), financial constraints, substance abuse (AOR 1.7, 95% CI 1.1-2.7), greater disease severity (AOR 1.8, 95% CI 1.5-2.2), medication side effects (AOR 2.4, 95% CI 1.2-4.6), and perceived stigma (AOR 3.2, 95% CI 1.1-5.3) emerged as significant risk factors. For anxiety, significant predictors were less social support (AOR 0.81, 95% CI 0.71-0.86), higher perceived stigma (AOR 2.2, 95% CI 1.1-6.3), greater disease severity (AOR 2.6, 95% CI 1.3-4.0), and more medication side effects (AOR 3.3, 95% CI 1.1-5.5). Prominent themes included psychological impacts like depression and anxiety, experiences of stigma and caretaking challenges, and recommendations for comprehensive patient support services. CONCLUSION: MDR-TB patients experience a substantially higher dual disease burden of depression and anxiety, elevating the risk for adverse outcomes and transmission. Improving psychosocial support is vital to patient-centric care pathways for vulnerable groups. Mixed methods provide comprehensive evidence to inform integrated physical and mental health services.

14.
Environ Toxicol Pharmacol ; 109: 104480, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825092

RESUMO

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

15.
Nature ; 630(8018): 1012-1019, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38778104

RESUMO

Early spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron1. Alternatively, it can occur through an exon-defined pathway2-5, whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5' splice site located directly downstream of it. The U4/U6.U5 tri-snRNP subsequently binds to produce a cross-intron (CI) or cross-exon (CE) pre-B complex, which is then converted to the spliceosomal B complex6,7. Exon definition promotes the splicing of upstream introns2,8,9 and plays a key part in alternative splicing regulation10-16. However, the three-dimensional structure of exon-defined spliceosomal complexes and the molecular mechanism of the conversion from a CE-organized to a CI-organized spliceosome, a pre-requisite for splicing catalysis, remain poorly understood. Here cryo-electron microscopy analyses of human CE pre-B complex and B-like complexes reveal extensive structural similarities with their CI counterparts. The results indicate that the CE and CI spliceosome assembly pathways converge already at the pre-B stage. Add-back experiments using purified CE pre-B complexes, coupled with cryo-electron microscopy, elucidate the order of the extensive remodelling events that accompany the formation of B complexes and B-like complexes. The molecular triggers and roles of B-specific proteins in these rearrangements are also identified. We show that CE pre-B complexes can productively bind in trans to a U1 snRNP-bound 5' splice site. Together, our studies provide new mechanistic insights into the CE to CI switch during spliceosome assembly and its effect on pre-mRNA splice site pairing at this stage.


Assuntos
Éxons , Íntrons , Splicing de RNA , Spliceossomos , Humanos , Processamento Alternativo , Microscopia Crioeletrônica , Éxons/genética , Íntrons/genética , Modelos Moleculares , Sítios de Splice de RNA/genética , Splicing de RNA/genética , Spliceossomos/metabolismo , Spliceossomos/química , Spliceossomos/ultraestrutura , Ribonucleoproteínas Nucleares Pequenas/química , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Ribonucleoproteínas Nucleares Pequenas/ultraestrutura
16.
Epilepsy Res ; 203: 107382, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761467

RESUMO

BACKGROUND: Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior. METHODS: Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control. RESULTS: Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286). CONCLUSIONS: Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Anticonvulsivantes , Comportamento Autodestrutivo , United States Food and Drug Administration , Humanos , Anticonvulsivantes/efeitos adversos , Comportamento Autodestrutivo/induzido quimicamente , Comportamento Autodestrutivo/epidemiologia , Estados Unidos/epidemiologia , Masculino , Feminino , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Adulto , Adolescente , Pessoa de Meia-Idade , Suicídio/estatística & dados numéricos , Adulto Jovem , Bases de Dados Factuais , Farmacovigilância , Criança , Idoso
17.
Chemosphere ; 360: 142312, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761824

RESUMO

Lignocellulosic waste generation and their improper disposal has accelerated the problems associated with increased greenhouse gas emissions and associated environmental pollution. Constructive ways to manage and mitigate the pollution associated with lignocellulosic waste has propelled the research on biochar production using lignocellulose-based substrates. The sustainability of various biochar production technologies in employing lignocellulosic biomass as feedstock for biochar production not only aids in the lignocellulosic biomass valorization but also helps in carbon neutralization and carbon utilization. Functionalization of biochar through various physicochemical methods helps in improving their functional properties majorly by reducing the size of the biochar particles to nanoscale and modifying their surface properties. The usage of engineered biochar as nano adsorbents for environmental applications like dye absorption, removal of organic pollutants and endocrine disrupting compounds from wastewater has been the thrust areas of research in the past few decades. This review presents a comprehensive outlook on the up-to-date research findings related to the production and engineering of biochar from lignocellulosic biomass and their applications in environmental remediation especially with respect to wastewater treatment. Further a detailed discussion on various biochar activation methods and the future scope of biochar research is presented in this review work.


Assuntos
Biomassa , Carvão Vegetal , Lignina , Carvão Vegetal/química , Lignina/química , Recuperação e Remediação Ambiental/métodos , Águas Residuárias/química , Adsorção , Poluentes Ambientais/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise
19.
Vaccines (Basel) ; 12(5)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38793749

RESUMO

Immunotherapies can treat many cancers, including difficult-to-treat cases such as lung cancer. Due to its tolerability, long-lasting therapeutic responses, and efficacy in a wide spectrum of patients, immunotherapy can also help to treat lung cancer, which has few treatment choices. Tumor-specific antigens (TSAs) for cancer vaccinations and T-cell therapies are difficult to discover. Neoantigens (NeoAgs) from genetic mutations, irregular RNA splicing, protein changes, or viral genetic sequences in tumor cells provide a solution. NeoAgs, unlike TSAs, are non-self and can cause an immunological response. Next-generation sequencing (NGS) and bioinformatics can swiftly detect and forecast tumor-specific NeoAgs. Highly immunogenic NeoAgs provide personalized or generalized cancer immunotherapies. Dendritic cells (DCs), which originate and regulate T-cell responses, are widely studied potential immunotherapeutic therapies for lung cancer and other cancers. DC vaccines are stable, reliable, and safe in clinical trials. The purpose of this article is to evaluate the current status, limitations, and prospective clinical applications of DC vaccines, as well as the identification and selection of major histocompatibility complex (MHC) class I and II genes for NeoAgs. Our goal is to explain DC biology and activate DC manipulation to help researchers create extremely potent cancer vaccines for patients.

20.
J Chem Inf Model ; 64(10): 4298-4309, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38700741

RESUMO

The intricate nature of the blood-brain barrier (BBB) poses a significant challenge in predicting drug permeability, which is crucial for assessing central nervous system (CNS) drug efficacy and safety. This research utilizes an innovative approach, the classification read-across structure-activity relationship (c-RASAR) framework, that leverages machine learning (ML) to enhance the accuracy of BBB permeability predictions. The c-RASAR framework seamlessly integrates principles from both read-across and QSAR methodologies, underscoring the need to consider similarity-related aspects during the development of the c-RASAR model. It is crucial to note that the primary goal of this research is not to introduce yet another model for predicting BBB permeability but rather to showcase the refinement in predicting the BBB permeability of organic compounds through the introduction of a c-RASAR approach. This groundbreaking methodology aims to elevate the accuracy of assessing neuropharmacological implications and streamline the process of drug development. In this study, an ML-based c-RASAR linear discriminant analysis (LDA) model was developed using a dataset of 7807 compounds, encompassing both BBB-permeable and -nonpermeable substances sourced from the B3DB database (freely accessible from https://github.com/theochem/B3DB), for predicting BBB permeability in lead discovery for CNS drugs. The model's predictive capability was then validated using three external sets: one containing 276,518 natural products (NPs) from the LOTUS database (accessible from https://lotus.naturalproducts.net/download) for data gap filling, another comprising 13,002 drug-like/drug compounds from the DrugBank database (available from https://go.drugbank.com/), and a third set of 56 FDA-approved drugs to assess the model's reliability. Further diversifying the predictive arsenal, various other ML-based c-RASAR models were also developed for comparison purposes. The proposed c-RASAR framework emerged as a powerful tool for predicting BBB permeability. This research not only advances the understanding of molecular determinants influencing CNS drug permeability but also provides a versatile computational platform for the rapid assessment of diverse compounds, facilitating informed decision-making in drug development and design.


Assuntos
Barreira Hematoencefálica , Aprendizado de Máquina , Permeabilidade , Relação Quantitativa Estrutura-Atividade , Barreira Hematoencefálica/metabolismo , Humanos , Análise Discriminante
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