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1.
Arch Pharm (Weinheim) ; : e2400418, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39086040

RESUMO

Green seaweed (Ulva sp.) is frequently used as a food component and nutraceutical agent because of its high polysaccharide and natural fiber content in Asian countries. This study investigates both metabolomic profiling of Ulva sp. and the neuroprotective efficacy of its ethanol extract and its underlying mechanisms in a rotenone-induced rat model of neurodegeneration, mimicking Parkinson's disease (PD) in humans. Metabolomic profiling of Ulva sp. extract was done using liquid chromatography high resolution electrospray ionization mass spectrometry and led to the identification of 22 compounds belonging to different chemical classes.Catenin Beta Additionally, this study demonstrated the neuroprotective properties against rotenone-induced PD, which was achieved through the suppression of elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 together with the inhibition of reactive oxygen species (ROS) generation, apoptosis, inflammatory mediators, and the phosphoinositide 3-kinases/serine/threonine protein kinase (PI3K/AKT) pathway. Using a protein-protein interaction network, AKT1, GAPDH, TNF-α, IL-6, caspase 3, signal transducer and activator of transcription 3, Catenin Beta 1, epidermal growth factor receptor, B-cell lymphoma -2, and HSP90AA1 were identified as the top 10 most significant genes. Finally, molecular docking results showed that compounds 1, 3, and 7 might possess a promising anti-parkinsonism effect by binding to active sites of selected hub genes. Therefore, it is hypothesized that the Ulva sp. extract has the potential to be further developed as a potential therapeutic agent for the treatment of PD.

2.
Chem Asian J ; : e202400362, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087987

RESUMO

Polycrystalline Pt electrode was employed to selectively convert nitrite ions ([[EQUATION]]) into useful nitrogenous compound through electrochemical reduction reaction in neutral medium. According to adsorptive stripping analysis, the reduction process produced nitric oxide (NO) on the surface of Pt electrode. The spectroscopic test and gas chromatographic studies discovered the presence of ammonia (NH3) in the electrolyzed solution, suggesting the transformation of adsorbed NO into NH3 during the reverse scan. Scan rate dependent investigation was performed to elucidate kinetic information relating to this reaction on Pt surface. From Ep vs scan rate (υ) and jp vs υ (logarithmic plot), it was found that the conversion of [[EQUATION]] ion into NO is an irreversible reaction which relies on the diffusion of [[EQUATION]] ions to electrode surface. The Tafel analysis unveiled that the first electron transfer sets the overall reaction rate, having formal reduction potential, E0' = -0.46 V and standard heterogeneous rate constant, k0 = [[EQUATION]] cm s-1. Reductive transfer coefficient (α) is another kinetics parameter, which was found to be approximate 0.77 from the difference between Ep and Ep/2 of the voltammograms obtained over scan rate range 0.005 V s-1 to 0.250 V s-1, indicating a stepwise process.

3.
bioRxiv ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39091889

RESUMO

Planarians are an excellent model for investigating molecular mechanisms necessary for regenerating a functional nervous system. Numerous studies have led to the generation of extensive genomic resources, especially whole-animal single-cell RNA-seq resources. These have facilitated in silico predictions of neuronal subtypes, many of which have been anatomically mapped by in situ hybridization. However, our knowledge of the function of dozens of neuronal subtypes remains poorly understood. Previous investigations identified that polycystic kidney disease (pkd)-like genes in planarians are strongly expressed in sensory neurons and have roles in mechanosensation. Here, we examine the expression and function of all the pkd genes found in the Schmidtea mediterranea genome and map their expression in the asexual and hermaphroditic strains. Using custom behavioral assays, we test the function of pkd genes in response to mechanical stimulation and in food detection. Our work provides insight into the physiological function of sensory neuron populations and protocols for creating inexpensive automated setups for acquiring and analyzing mechanosensory stimulation in planarians.

4.
Heliyon ; 10(13): e33858, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39055814

RESUMO

Background: Marfan Syndrome (MFS), a genetic disorder impacting connective tissue, manifests in a wide array of phenotypes which can affect numerous bodily systems, especially the thoracic aorta. The syndrome often presents distinct facial features that potentially allow for diagnostic clinical recognition. Herein, we explore the potential of Artificial Intelligence (AI) in diagnosing Marfan syndrome from ordinary facial images, as assessed by overall accuracy, F1 score, and area under the ROC curve. Methods: This study explores the utilization of Convolutional Neural Networks (CNN) for MFS identification through facial images, offering a novel, non-invasive, automated, and computerized diagnostic approach. The research examines the accuracy of Neural Networks in the diagnosis of Marfan Disease from ordinary on-line facial images. The model was trained on 80 % of 672 facial images (182 Marfan and 490 control). The other 20 % of images were used as the test set. Results: Overall accuracy was 98.5 % (0 % false positive, 2 % false negative). F1 score was 97 % for Marfan facies and 99 % for non-Marfan facies. Area under the ROC curve was 100 %. Conclusion: An Artificial Intelligence (AI) program was able to distinguish Marfan from non-Marfan facial images (from ordinary on-line photographs) with an extremely high degree of accuracy. Clinical usefulness of this program is anticipated. However, due to the limited and preliminary nature of this work, this should be viewed as only a pilot study.

5.
Hematol Rep ; 16(3): 479-486, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39051419

RESUMO

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT's efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.

6.
Discov Med ; 36(186): 1513-1526, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39054721

RESUMO

BACKGROUND: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019 in Wuhan, China. Genome-wide association studies (GWAS) have significantly expanded our comprehension of how specific genetic variations are linked to diseases. Research has demonstrated the existence of genetic factors influencing susceptibility to coronaviruses. The objective of this study was to examine the association of certain loci with the COVID-19 in Saudi population. METHODS: In the present study we have examined the link between the COVID-19 disease and certain genetic variants in hospitalized COVID-19 patients (n = 16) in Tabuk and Bisha, Kingdom Saudi Arabia. We used the genome Analysis Toolkit (GATK) and Comprehensive variant annotation was performed different databases and tools such as Search Tool for the Retrieval of Interacting Genes (STRING), PanelApp and PolyPhen-2. RESULTS: The study showed that the genetic variants associated with genes such as Homeostatic Iron Regulator (HFE) (found in 7 patients, representing 44%), complement factor H (CFH) (6 patients, 38%), cadherin 23 (CDH23) (4 patients, 25%), cytotoxic T-lymphocyte associated protein 4 (CTLA-4) (3 patients, 19%), Transforming Growth Factor Beta 1 (TGFB1) (3 patients, 19%), CREB-binding protein (CREBBP) (2 patients, 13%), E1A Binding Protein P300 (EP300) (2 patients, 13%), hemoglobin subunit beta (HBB) (2 patients, 13%), interferon regulatory factor 7 (IRF7) (2 patients, 13%), and unc-119 lipid binding chaperone (UNC119) (2 patients, 13%) might be associated with susceptibility to coronavirus. We also identified mutations in the COVID-19 patient that are pathogenic or likely pathogenic. CONCLUSION: A recurrent pathogenic mutation, HFE p.His63Asp (H63D), was identified in 7 patients, suggesting its potential contribution to disease severity. Additionally, a likely pathogenic variant, HBB p.Glu7Val (E7V), was present in 2 patients, highlighting its potential role in disease susceptibility. Our results shed light on the key genetic mechanisms of COVID-19 pathogenesis and help to identify and stratify the individuals or populations that are at risk to corona virus infection. The identification of susceptible individuals or populations assist in prevention and/or in treatment programs.


Assuntos
COVID-19 , Sequenciamento do Exoma , Proteína da Hemocromatose , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/virologia , COVID-19/mortalidade , SARS-CoV-2/genética , Masculino , Pessoa de Meia-Idade , Feminino , Arábia Saudita/epidemiologia , Proteína da Hemocromatose/genética , Adulto , Predisposição Genética para Doença , Idoso , Mutação , Estudo de Associação Genômica Ampla
7.
Risk Manag Healthc Policy ; 17: 1745-1756, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979106

RESUMO

Introduction: This study aimed to evaluate disaster preparedness and management among an inter-professional team at the Royal Commission Hospital (RCH) in Jubail, Saudi Arabia. Methods: Conducted between May and July 2023, this cross-sectional study involved healthcare providers in both patient-facing and non-patient-facing roles. Participants responded to a comprehensive online questionnaire comprising 22 questions across seven sections covering aspects of emergency response, disaster management, and infection control. The study targeted a minimum sample size of 500 participants, successfully garnering responses from 512 individuals. Results: Of the 512 participants, 59.9% (n=312) were healthcare providers in patient-facing roles, and 40.1% (n=209) were in non-patient-facing roles. The results revealed notable disparities in awareness and preparedness between these two groups. Healthcare providers demonstrated higher awareness levels compared to their non-patient-facing counterparts. For instance, 76.9% of healthcare providers were aware of the hospital's emergency response plan compared to 56.2% of non-healthcare providers (χ² = 52.165, p < 0.001). Similar disparities were observed in understanding the term "disaster" (86.5% vs 54.1%, χ² = 27.931, p < 0.001), and awareness of a command center (73.4% vs 45.2%, χ² = 42.934, p < 0.001). Discussion: These findings underscore the critical need for enhancing awareness, education, and preparedness within healthcare facilities, emphasizing an integrated approach that includes both healthcare and non-healthcare staff. By addressing these gaps, healthcare facilities can significantly improve their emergency response efficiency, disaster management capabilities, and infection control measures, thereby enhancing the overall safety and quality of patient care.

8.
Sensors (Basel) ; 24(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39001012

RESUMO

Wearable alcohol monitoring devices demand noninvasive, real-time measurement of blood alcohol content (BAC) reliably and continuously. A few commercial devices are available to determine BAC noninvasively by detecting transcutaneous diffused alcohol. However, they suffer from a lack of accuracy and reliability in the determination of BAC in real time due to the complex scenario of the human skin for transcutaneous alcohol diffusion and numerous factors (e.g., skin thickness, kinetics of alcohol, body weight, age, sex, metabolism rate, etc.). In this work, a transcutaneous alcohol diffusion model has been developed from real-time captured data from human wrists to better understand the kinetics of diffused alcohol from blood to different skin epidermis layers. Such a model will be a footprint to determine a base computational model in larger studies. Eight anonymous volunteers participated in this pilot study. A laboratory-built wearable blood alcohol content (BAC) monitoring device collected all the data to develop this diffusion model. The proton exchange membrane fuel cell (PEMFC) sensor was fabricated and integrated with an nRF51822 microcontroller, LMP91000 miniaturized potentiostat, 2.4 GHz transceiver supporting Bluetooth low energy (BLE), and all the necessary electronic components to build this wearable BAC monitoring device. The %BAC data in real time were collected using this device from these volunteers' wrists and stored in the end device (e.g., smartphone). From the captured data, we demonstrate how the volatile alcohol concentration on the skin varies over time by comparing the alcohol concentration in the initial stage (= 10 min) and later time (= 100 min). We also compare the experimental results with the outputs of three different input profiles: piecewise linear, exponential linear, and Hoerl, to optimize the developed diffusion model. Our results demonstrate that the exponential linear function best fits the experimental data compared to the piecewise linear and Hoerl functions. Moreover, we have studied the impact of skin epidermis thickness within ±20% and demonstrate that a 20% decrease in this thickness results in faster dynamics compared to thicker skin. The model clearly shows how the diffusion front changes within a skin epidermis layer with time. We further verified that 60 min was roughly the time to reach the maximum concentration, Cmax, in the stratum corneum from the transient analysis. Lastly, we found that a more significant time difference between BACmax and Cmax was due to greater alcohol consumption for a fixed absorption time.


Assuntos
Concentração Alcoólica no Sangue , Pele , Dispositivos Eletrônicos Vestíveis , Humanos , Pele/metabolismo , Pele/química , Etanol/sangue , Etanol/análise , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Difusão , Adulto , Masculino , Feminino
9.
Cancers (Basel) ; 16(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39001554

RESUMO

BACKGROUND: This study aimed to estimate the relative efficacy of neoadjuvant nivolumab in combination with chemotherapy (neoNIVO + CT) compared to relevant treatments amongst resectable non-metastatic non-small-cell lung cancer (rNSCLC) patients. METHODS: Treatment comparisons were based on a network meta-analysis (NMA) using randomized clinical trial data identified via systematic literature review (SLR). The outcomes of interest were event-free survival (EFS) and pathological complete response (pCR). NeoNIVO + CT was compared to neoadjuvant chemotherapy (neoCT), neoadjuvant chemoradiotherapy (neoCRT), adjuvant chemotherapy (adjCT), and surgery alone (S). Due to the potential for effect modification by stage, all-stage and stage-specific networks were considered. Fixed-effect (FE) and random-effects Bayesian NMA models were run (EFS = hazard ratios [HR]; pCR = odds ratios [OR]; 95% credible intervals [CrI]). RESULTS: Sixty-one RCTs were identified (base case = 9 RCTs [n = 1978 patients]). In the all-stages FE model, neoNIVO + CT had statistically significant EFS improvements relative to neoCT (HR = 0.68 [95% CrI: 0.49, 0.94]), S (0.59 [0.42, 0.82]), adjCT (0.66 [0.45, 0.96]), but not relative to neoCRT (HR = 0.77 [0.52, 1.16]). NeoNIVO + CT (5 RCTs) had statistically significant higher odds of pCR relative to neoCT (OR = 12.53 [5.60, 33.82]) and neoCRT (7.15 [2.31, 24.34]). Stage-specific model findings were consistent. CONCLUSIONS: This NMA signals improved EFS and/or pCR of neoNIVO + CT relative to comparators among patients with rNSCLC.

10.
J Med Cases ; 15(7): 126-129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38993809

RESUMO

Renal cell carcinoma (RCC) is notorious for spreading to various organs, however, its occurrence in the gastrointestinal (GI) tract is uncommon and poses diagnostic challenges due to vague symptoms. Here, we present the case of a 64-year-old man experiencing recurrent RCC metastasis in the GI tract. He presented with multiple episodes of hematochezia and was found to have masses in the colon, liver, and peritoneum, with histopathology confirming RCC. The patient underwent systemic chemotherapy and palliative radiation therapy, leading to symptom relief. This case emphasizes the rarity of RCC metastasizing to the GI tract and the importance of timely recognition and frequent surveillance during the remission phase to detect recurrence.

11.
medRxiv ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38978639

RESUMO

Background: Available live-oral rotavirus vaccines are associated with low to moderate performance in low- and middle-income settings. There is limited evidence relating to how the vaccine dosing schedule might be adjusted to improve vaccine performance in these settings. Methods: We used mathematical models fitted to rotavirus surveillance data for children <5 years of age from three different hospitals in Ghana (Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi and War Memorial Hospital in Navrongo) to project the impact of rotavirus vaccination over a 10-year period (April 2012-March 2022). We quantified and compared the impact of the previous vaccination program in Ghana to the model-predicted impact for other vaccine dosing schedules across the three hospitals and the entire country, under different assumptions about vaccine protection. To project the rotavirus vaccine impact over Ghana, we sampled from the range of model parameters for Accra and Navrongo, assuming that these two settings represent the "extremes" of rotavirus epidemiology within Ghana. Results: For the previously implemented 6/10-week monovalent Rotarix vaccine (RV1) schedule, the model-estimated average annual incidence of moderate-to-severe rotavirus-associated gastroenteritis (RVGE) ranged between 1,151 and 3,002 per 100,000 people per year over the 10-year period for the three sites. Compared to no vaccination, the model-estimated median percentage reductions in RVGE ranged from 28-85% and 12-71% among children <1 year and <5 years of age respectively, with the highest and lowest percentage reductions predicted using model parameters estimated for Accra and Navrongo, respectively. The median predicted reductions in RVGE for the whole country ranged from 57-66% and 35-45% among children <1 year and <5 years of age, respectively. The 1/6/10- and 6/10/14-week schedules provided the best and comparable reductions in RVGE compared to the original 6/10-week schedule, whereas there was no improvement in impact for the 10/14-week schedule. Conclusions: We found that administering an additional dose of RV1 might be an effective strategy to improve rotavirus vaccine impact, particularly in settings with low vaccine effectiveness. The results could be extrapolated to other countries using a 2-dose vaccine schedule with low to moderate vaccine performance.

13.
Curr Drug Deliv ; 21(10): 1285-1299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39034714

RESUMO

The field of microfluidics encompasses the study of fluid behavior within micro-channels and the development of miniature systems featuring internal compartments or passageways tailored for fluid control and manipulation. Microfluidic devices capitalize on the unique chemical and physical properties exhibited by fluids at the microscopic scale. In contrast to their larger counterparts, microfluidic systems offer a multitude of advantages. Their implementation facilitates the investigation and utilization of reduced sample, solvent, and reagent volumes, thus yielding decreased operational expenses. Owing to their compact dimensions, these devices allow for the concurrent execution of multiple procedures, leading to expedited experimental timelines. Over the past two decades, microfluidics has undergone remarkable advancements, evolving into a multifaceted discipline. Subfields such as organ-on-a-chip and paper-based microfluidics have matured into distinct fields of study. Nonetheless, while scientific progress within the microfluidics realm has been notable, its translation into autonomous end-user applications remains a frontier to be fully explored. This paper sets forth the central objective of scrutinizing the present research paradigm, prevailing limitations, and potential prospects of customizable microfluidic devices. Our inquiry revolves around the latest strides achieved, prevailing constraints, and conceivable trajectories for adaptable microfluidic technologies. We meticulously delineate existing iterations of microfluidic systems, elucidate their operational principles, deliberate upon encountered limitations, and provide a visionary outlook toward the future trajectory of microfluidic advancements. In summation, this work endeavors to shed light on the current state of microfluidic systems, underscore their operative intricacies, address incumbent challenges, and unveil promising pathways that chart the course toward the next frontier of microfluidic innovation.


Assuntos
Dispositivos Lab-On-A-Chip , Humanos , Microfluídica/instrumentação , Microfluídica/tendências , Técnicas Analíticas Microfluídicas/instrumentação , Desenho de Equipamento/tendências
14.
J Multidiscip Healthc ; 17: 3265-3281, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006872

RESUMO

Background: Cigarette smoking is one of the world's largest avoidable risk factors for morbidity and mortality. Numerous studies have investigated the association between smoking and hypertension (HTN). Although observational data and cross-sectional research often exhibit a link between smoking and HTN, establishing causation remains challenging owing to potential confounding variables. Mendelian randomization (MR), a genetic epidemiological technique that employs genetic variants as instrumental variables, offers a more robust approach for evaluating causal links. This review aimed to explore both the observational and causal relationships between smoking and the risk of HTN. Methodology: A comprehensive literature search across major electronic databases was conducted to identify relevant observational and Mendelian randomization (MR) studies on smoking and HTN risk. Various characteristics were included during study selection, such as study design, exposure assessment, and age range. Standardized processes were used for data retrieval and quality evaluation. Results: Analysis of observational data revealed a paradoxical association between smoking and the risk of HTN, where a lower risk was observed among current smokers when compared to non-smokers. However, observational analysis also presented a dose-response effect with greater smoking intensity showed a modest linear increase in HTN risk, and older smoking initiation was associated with a slight increase in HTN risk (compared with younger). In contrast, MR-based causal estimates provide inconsistent evidence regarding the causal relationship between smoking behavior and HTN. Some MR analyses indicated a potential causal link between smoking and HTN; but this was not consistent. Conclusion: Observational studies suggest a paradoxical association between smoking and HTN. However, MR studies do not provide sufficient evidence to establish a causal relationship. Regardless, lifestyle variables remain crucial for overall health. Healthcare professionals should regularly assess smoking status and provide counseling for quitting. Further research is needed to clarify the underlying processes, identify mediators, and evaluate the interventions.

15.
Cureus ; 16(6): e62740, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39036268

RESUMO

Umbilical venous catheterization is a common procedure in the neonatal care unit. Although it is an easy procedure, insertion under suboptimal techniques may have devastating effects on the newborn. We present a rare case of umbilical venous catheter (UVC) malposition complicated with respiratory distress, pleural effusion, and acute kidney injury.

16.
bioRxiv ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39026851

RESUMO

Helicases have emerged as promising targets for the development of antiviral drugs; however, the family remains largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all available helicases from the ChEMBL database. After thoroughly curating and enriching the data with relevant annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC (Helicase-targeting SMAll Molecule Compound Collection). The current version of Heli-SMACC contains 20,432 bioactivity entries for viral, human, and bacterial helicases. We have selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available at https://smacc.mml.unc.edu.

17.
RSC Adv ; 14(31): 22548-22559, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39021456

RESUMO

The genus Hertia, which belongs to the Asteraceae family, is a flowering genus with 12 species found in Africa, North and South. Among the species present in Algeria, Hertia cheirifolia L. is distributed in the eastern regions of Algeria. The aim of this study is to evaluate its phytochemical composition with following pharmacological assessments: the antioxidant, antibacterial, and antifungal activities of Hertia cheirifolia L. essential oil (EO). GC-MS analysis was used to analyze the chemical constituents of H. cheirifolia essential oil. The antioxidant capacity was assessed using DPPH, FRAP, and H2O2 tests. The EO was also tested for its ability to inhibit six strains of microorganisms, including two Gram (+) and four Gram (-) strains. The antifungal activity was tested by analyzing the effect of the EO on the mycelial growth of Fusarium oxysporum f.sp. lycopersici (FOL) fungi. Results showed that primary volatile components were α-pinene (32.59%), 2-(1-cyclopent-1-enyl-1-methylethyl) cyclopentanone (14.62%), (-)-germacrene D (11.37%), and bakkenolide A (9.57%). H. cheirifolia EO showed inhibitory effects against DPPH, H2O2, and FRAP (IC50 = 0.34 ± 0.1, 0.053 ± 0.1, and 0.047 ± 0.01 mg mL-1, respectively). The EO also exhibited moderate antibacterial effects against Staphylococcus aureus ATCC 25923 (S. aureus), Streptococcus pneumoniae ATCC 49619 (S. pneumoniae), and Enterobacter aerogenes ATCC 13048 (E. aerogenes), as well as significant antioxidant potential and varied antifungal activity based on dosage and fungal strain. To our knowledge, no previous research has examined the antifungal capacity of H. cheirifolia oil and oil-mycelial development of the FOL relationship. To fully explore the benefits of H. cheirifolia EO, more in vivo research is necessary, along with more testing on other bacterial and fungal strains.

18.
Macromol Rapid Commun ; : e2400363, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38950314

RESUMO

Herein, fluorescent conducting tautomeric polymers (FCTPs) are developed by polymerizing 2-methylprop-2-enoic acid (MPEA), methyl-2-methylpropenoate (MMP), N-(propan-2-yl)prop-2-enamide (PPE), and in situ-anchored 3-(N-(propan-2-yl)prop-2-enamido)-2-methylpropanoic acid (PPEMPA). Among as-synthesized FCTPs, the most promising characteristics in FCTP3 are confirmed by NMR and Fourier transform infrared (FTIR) spectroscopies, luminescence enhancements, and computational studies. In FCTP3, ─C(═O)NH─, -C(═O)N<, ─C(═O)OH, and ─C(═O)OCH3 subluminophores are identified by theoretical calculations and experimental analyses. These subluminophores facilitate redox characteristics, solid state emissions, aggregation-enhanced emissions (AEEs), excited-state intramolecular proton transfer (ESIPT), and conductivities in FCTP3. The ESIPT-associated dual emission/AEEs of FCTP3 are elucidated by time correlated single photon counting (TCSPC) investigation, solvent polarity effects, concentration-dependent emissions, dynamic light scattering (DLS) measurements, field emission scanning electron microscopy images, and computational calculations. The cyclic voltammetry measurements of FCTP3 indicate cumulative redox efficacy of ─C(═O)OH, ─C(═O)NH─/-C(═O)N<, ─C(─O─)═NH+─/─C(─O─)═N+, and ─C(═N)OH functionalities. In FCTP3, ESIPT-associated dual-emission enable in the selective detection of Cr(III)/Cu(II) at λem1/λem2 with the limit of detection of 0.0343/0.079 ppb. The preferential interaction of Cr(III)/Cu(II) with FCTP3 (amide)/FCTP3 (imidol) and oxidation/reduction of Cr(III)/Cu(II) to Cr(VI)/Cu(I) are further supported by NMR-titration; FTIR and X-ray photoelectron spectroscopy analyses; TCSPC/electrochemical/DLS measurement; alongside theoretical calculations. The proton conductivity of FCTP3 is explored by electrochemical impedance spectroscopy and I-V measurements.

19.
AAPS PharmSciTech ; 25(6): 160, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992299

RESUMO

In part I, we reported Hansen solubility parameters (HSP, HSPiP program), experimental solubility at varied temperatures for TOTA delivery. Here, we studied dose volume selection, stability, pH, osmolality, dispersion, clarity, and viscosity of the explored combinations (I-VI). Ex vivo permeation and deposition studies were performed to observe relative diffusion rate from the injected site in rat skin. Confocal laser scanning microscopy (CLSM) study was conducted to support ex vivo findings. Moreover, GastroPlus predicted in vivo parameters in humans and the impact of various critical factors on pharmacokinetic parameters (PK). Immediate release product (IR) contained 60% of PEG400 whereas controlled release formulation (CR) contained PEG400 (60%), water (10%) and d-limonene (30%) to deliver 2 mg of TOTA. GastroPlus predicted the plasma drug concentration of weakly basic TOTA as function of pH (from pH 2.0 to 9). The cumulative drug permeation and drug deposition were found to be in the order as B-VI˃ C-VI˃A-VI across rat skin. This finding was further supported with CLSM. Moreover, IR and CR were predicted to achieve Cmax of 0.0038 µg/ mL and 0.00023 µg/mL, respectively, after sub-Q delivery. Added limonene in CR extended the plasma drug concentration over period of 12 h as predicted in GastroPlus. Parameters sensitivity analysis (PSA) assessment predicted that sub-Q blood flow rate is the only factor affecting PK parameters in IR formulation whereas this was insignificant for CR. Thus, sub-Q delivery CR would be promising alternative with ease of delivery to children and aged patient.


Assuntos
Absorção Cutânea , Solubilidade , Tartarato de Tolterodina , Animais , Ratos , Humanos , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Tartarato de Tolterodina/administração & dosagem , Tartarato de Tolterodina/farmacocinética , Termodinâmica , Solventes/química , Pele/metabolismo , Concentração de Íons de Hidrogênio , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Terpenos/química , Terpenos/administração & dosagem , Terpenos/farmacocinética , Administração Cutânea , Limoneno/administração & dosagem , Limoneno/farmacocinética , Limoneno/química , Masculino , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos/métodos , Química Farmacêutica/métodos , Cicloexenos/química , Cicloexenos/farmacocinética , Cicloexenos/administração & dosagem , Ratos Sprague-Dawley
20.
medRxiv ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38947006

RESUMO

Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making accurate measurement a critical parameter in PT evaluation. Echocardiograms are commonly used for measuring EF, but human interpretation has limitations in terms of intra- and inter-observer (or reader) variance. Deep learning (DL) has driven a resurgence in machine learning, leading to advancements in medical applications. We introduce the ViViEchoformer DL approach, which uses a video vision transformer to directly regress the left ventricular function (LVEF) from echocardiogram videos. The study used a dataset of 10,030 apical-4-chamber echocardiography videos from patients at Stanford University Hospital. The model accurately captures spatial information and preserves inter-frame relationships by extracting spatiotemporal tokens from video input, allowing for accurate, fully automatic EF predictions that aid human assessment and analysis. The ViViEchoformer's prediction of ejection fraction has a mean absolute error of 6.14%, a root mean squared error of 8.4%, a mean squared log error of 0.04, and an R 2 of 0.55. ViViEchoformer predicted heart failure with reduced ejection fraction (HFrEF) with an area under the curve of 0.83 and a classification accuracy of 87 using a standard threshold of less than 50% ejection fraction. Our video-based method provides precise left ventricular function quantification, offering a reliable alternative to human evaluation and establishing a fundamental basis for echocardiogram interpretation.

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