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1.
Medicine (Baltimore) ; 103(38): e39738, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312379

RESUMO

Early recognition of severe acute pancreatitis (AP) is crucial for timely intervention. This study aims to evaluate the prognostic accuracy of the Emergency Room Assessment of AP (ERAP) score and compare it with the Bedside Index for Severity in AP (BISAP) score in predicting severe AP, mortality, and persistent multiple organ failure (MOF) in Vietnamese patients. This prospective cohort study included AP patients admitted to Cho Ray Hospital between August 2021 and May 2022. Patient data, including demographics, clinical presentations, and laboratory results, were collected upon admission. The ERAP and BISAP scores were calculated from these admission data. The prognostic accuracy for severe AP, mortality, and persistent MOF was assessed via the area under the receiver-operating characteristic curve (AUC). Among 167 AP patients (mean age 41.5 ±â€…12.0 years), hypertriglyceridemia (34.7%) and alcohol (22.2%) were the most prevalent etiologies. Severe AP accounted for 33.5% of the patients. Mortality rates were higher in persistent MOF patients (42.9%) than in persistent single-organ failure patients (3.6%), with a P value <.001. The ERAP score had AUCs for predicting severe AP, mortality, and persistent MOF of 0.899, 0.817, and 0.867, respectively, with an optimal cutoff of ≥2. The ERAP score had a better prognostic value than the BISAP score in predicting severe AP (AUC: 0.899 vs 0.820; P = .0072) and persistent MOF (AUC: 0.867 vs 0.785; P = .0193) but had a similar prognostic value for mortality (AUC: 0.817 vs 0.728; P = .0628). The ERAP score has strong predictive value for severe AP and persistent MOF, surpassing the BISAP score in these categories while maintaining similar accuracy for mortality prediction in the Vietnamese population. The ERAP score can be a valuable tool for the early identification of high-risk AP patients, enabling timely and appropriate clinical interventions.


Assuntos
Pancreatite , Índice de Gravidade de Doença , Humanos , Masculino , Pancreatite/mortalidade , Pancreatite/diagnóstico , Pancreatite/complicações , Feminino , Adulto , Prognóstico , Vietnã/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Curva ROC , Serviço Hospitalar de Emergência/estatística & dados numéricos , População do Sudeste Asiático
2.
Mycoses ; 67(9): e13795, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39304967

RESUMO

BACKGROUND: Terbinafine is widely used to treat onychomycosis caused by dermatophyte fungi. Terbinafine resistance in recent years is causing concern. Resistance has so far been associated with single-nucleotide substitutions in the DNA sequence of the enzyme squalene epoxidase (SQLE) but how this affects SQLE functionality is not understood. OBJECTIVES: The aim of this study was to understand newly discovered resistance in two Australian strains of Trichophyton interdigitale. PATIENTS/METHODS: Resistance to terbinafine was tested in four newly isolated strains. Three-dimensional SQLE models were prepared to investigate how the structure of their SQLE affected the binding of terbinafine. RESULTS: This study found the first Australian occurrences of terbinafine resistance in two T. interdigitale strains. Both strains had novel deletion mutations in erg1 and frameshifts during translation. Three-dimensional models had smaller SQLE proteins and open reading frames as well as fewer C-terminal α-helices than susceptible strains. In susceptible strains, the lipophilic tail of terbinafine was predicted to dock stably into a hydrophobic pocket in SQLE lined by over 20 hydrophobic amino acids. In resistant strains, molecular dynamics simulations showed that terbinafine docking was unstable and so terbinafine did not block squalene metabolism and ultimately ergosterol production. The resistant reference strain ATCC MYA-4438 T. rubrum showed a single erg1 mutation that resulted in frameshift during translation, leading to C-terminal helix deletion. CONCLUSIONS: Modelling their effects on their SQLE proteins will aid in the design of potential new treatments for these novel resistant strains, which pose clinical problems in treating dermatophyte infections with terbinafine.


Assuntos
Antifúngicos , Arthrodermataceae , Farmacorresistência Fúngica , Esqualeno Mono-Oxigenase , Terbinafina , Terbinafina/farmacologia , Esqualeno Mono-Oxigenase/genética , Esqualeno Mono-Oxigenase/metabolismo , Farmacorresistência Fúngica/genética , Austrália , Antifúngicos/farmacologia , Humanos , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Arthrodermataceae/enzimologia , Testes de Sensibilidade Microbiana , Onicomicose/microbiologia , Onicomicose/tratamento farmacológico , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Modelos Moleculares
3.
J Int Med Res ; 52(9): 3000605241277401, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39238276

RESUMO

Eosinophilic gastroenteritis poses a significant diagnostic challenge, particularly in developing countries, where the awareness of this condition may be limited. Here, the case of a patient in her early 30s, who presented with recurrent episodes of abdominal pain and diarrhea, is reported. Initial standard laboratory investigations revealed normal complete blood counts and elevated total serum immunoglobulin E levels. Upper and lower endoscopic evaluations with systemic biopsies did not reveal any significant abnormalities. However, computed tomography revealed a thickened small intestine wall, halo signs, and mild ascites. Analysis of the ascitic fluid confirmed eosinophilia. These findings prompted a diagnosis of eosinophilic gastroenteritis. The patient responded well to a targeted elimination diet, corticosteroids, and antileukotriene medication. The present case emphasizes the importance of considering eosinophilic gastroenteritis in the differential diagnosis of patients who present with abdominal pain and eosinophilic ascites.


Assuntos
Ascite , Enterite , Eosinofilia , Gastrite , Humanos , Eosinofilia/diagnóstico , Eosinofilia/patologia , Ascite/diagnóstico , Ascite/patologia , Ascite/etiologia , Feminino , Enterite/diagnóstico , Enterite/patologia , Vietnã , Gastrite/diagnóstico , Gastrite/patologia , Gastrite/complicações , Adulto , Tomografia Computadorizada por Raios X , Dor Abdominal/etiologia , Dor Abdominal/diagnóstico , Diagnóstico Diferencial
4.
Heliyon ; 10(15): e34992, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39157403

RESUMO

The aim of the present study was to evaluate the effect of the ethyl acetate fraction of amla (EAFA) extract on valproic acid (VPA)-induced postnatal autism in BALB/c mice. Our study revealed that mice treated with VPA on postnatal day 14 (PND14) showed significant abnormal behaviours such as social interaction, social affiliation, anxiety, and motor coordination compared to the control group, while EAFA extract treatment (100 mg/kg) ameliorated these symptoms. Our study highlights the protective effect of EAFA extract on improving behavioural alterations, significantly restoring anti-oxidative enzymes such as GST and GR, and reducing MDA and NO levels. Furthermore, the EAFA-treated group significantly lowered the proinflammatory markers (IL-1ß and TNF-α) and the expression of up-regulated 5-HT1D, 5-HT2A, and D2 receptor proteins. Based on histopathological studies, the percentage of neuronal injury in the EAFA-treated group as well as cellular structural changes were reduced using SEM analysis. In conclusion, the present study suggests that treatment with EAFA extract ameliorates VPA-induced autism due to its anti-oxidant and neuroprotective activity.

5.
Medicine (Baltimore) ; 103(27): e38752, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968516

RESUMO

The JNET classification, combined with magnified narrowband imaging (NBI), is essential for predicting the histology of colorectal polyps and guiding personalized treatment strategies. Despite its recognized utility, the diagnostic efficacy of JNET classification using NBI with dual focus (DF) magnification requires exploration in the Vietnamese context. This study aimed to investigate the diagnostic performance of the JNET classification with the NBI-DF mode in predicting the histology of colorectal polyps in Vietnam. A cross-sectional study was conducted at the University Medical Center in Ho Chi Minh City, Vietnam. During real-time endoscopy, endoscopists evaluated the lesion characteristics and recorded optical diagnoses using the dual focus mode magnification according to the JNET classification. En bloc lesion resection (endoscopic or surgical) provided the final pathology, serving as the reference standard for optical diagnoses. A total of 739 patients with 1353 lesions were recruited between October 2021 and March 2023. The overall concordance with the JNET classification was 86.9%. Specificities and positive predictive values for JNET types were: type 1 (95.7%, 88.3%); type 2A (81.4%, 90%); type 2B (96.6%, 54.7%); and type 3 (99.9%, 93.3%). The sensitivity and negative predictive value for differentiating neoplastic from non-neoplastic lesions were 97.8% and 88.3%, respectively. However, the sensitivity for distinguishing malignant from benign neoplasia was lower at 64.1%, despite a specificity of 95.9%. Notably, the specificity and positive predictive value for identifying deep submucosal cancer were high at 99.8% and 93.3%. In Vietnam, applying the JNET classification with NBI-DF demonstrates significant value in predicting the histology of colorectal polyps. This classification guides treatment decisions and prevents unnecessary surgeries.


Assuntos
Pólipos do Colo , Colonoscopia , Imagem de Banda Estreita , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/classificação , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/classificação , Neoplasias Colorretais/patologia , Estudos Transversais , Imagem de Banda Estreita/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , População do Sudeste Asiático , Vietnã
6.
Korean J Gastroenterol ; 83(6): 247-252, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918038

RESUMO

Toxocariasis, a zoonotic infection transmitted by Toxocara canis (from dogs) and Toxocara cati (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by Toxocara canis in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by Toxocara canis. Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a Toxocara canis-induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.


Assuntos
Albendazol , Larva Migrans Visceral , Tomografia Computadorizada por Raios X , Toxocara canis , Humanos , Toxocara canis/isolamento & purificação , Larva Migrans Visceral/diagnóstico , Larva Migrans Visceral/tratamento farmacológico , Masculino , Animais , Adulto Jovem , Albendazol/uso terapêutico , Cães , Fígado/parasitologia , Fígado/patologia , Anticorpos Anti-Helmínticos/sangue , Ultrassonografia , Abscesso Hepático/diagnóstico , Abscesso Hepático/parasitologia , Abscesso Hepático/tratamento farmacológico , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Imunoglobulina E/sangue , Anti-Helmínticos/uso terapêutico
7.
JGH Open ; 8(6): e13101, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38882631

RESUMO

Background and Aim: Accurate prediction of severe acute pancreatitis (SAP) is crucial for timely intervention. This study focuses on the Systemic Inflammatory Response Index (SIRI) to assess its clinical value in predicting the severity of AP in the Vietnamese context. Methods: A cross-sectional prospective study was conducted with acute pancreatitis patients at a national hospital in Ho Chi Minh City. The patients were classified into nonsevere and severe groups, and the clinical characteristics were analyzed. The predictive abilities of SIRI, calculated using neutrophil × monocyte/lymphocyte, was assessed for predictive abilities. Multivariate regression and receiver operating characteristics (ROC) curves evaluated the prognostic factors and predictive accuracy. Results: Among 207 patients, 78.7% had nonsevere AP, and 21.3% had SAP. The severe group exhibited a significantly higher median SIRI (12.0) than the nonsevere group (4.9) (P < 0.001). Multivariate regression identified SIRI (odds ratio [OR] = 1.623) as an independent predictor of SAP. The ROC curve determined a SIRI cutoff of 7.82 with an area under the curve (AUC) of 0.737. Combining the SIRI and Bedside Index for Severity in Acute Pancreatitis (BISAP) score improved the predictive ability (AUC = 0.820) with increased sensitivity (90.91%) (P < 0.001). Conclusion: SIRI, particularly when combined with the BISAP score, shows significant potential to predict SAP severity in the Vietnamese clinical setting, providing valuable information for effective patient management.

8.
JGH Open ; 8(5): e13058, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38737501

RESUMO

Background and Aim: Small rectosigmoid colorectal polyps (<10 mm) are prevalent, with a low prevalence of advanced neoplastic lesions. The "diagnose-and-leave" strategy, employing narrow band imaging (NBI), is gaining popularity for its safety and cost-effectiveness by reducing polypectomy complications and minimizing histopathology expenses. This study assessed the diagnostic efficacy of NBI with dual focus (DF) magnification for real-time neoplastic prediction of rectosigmoid polyps and explored the feasibility of implementing this strategy in Vietnam. Methods: In a prospective single-center study, 307 rectosigmoid polyps from 245 patients were analyzed using three consecutive endoscopic modes: white light endoscopy (WLE), NBI, and NBI-DF. Endoscopists assessed polyps for size, location, macroscopic shape, optical diagnosis, and confidence levels before histopathological evaluation. High confidence was assigned when the polyp exhibited all features of a single histology type. Predictions were compared with final histopathology results. Results: Of the total, 237 (77.2%) were diminutive (≤5 mm) polyps, and 18 (5.8%) were advanced neoplastic lesions. WLE + NBI and WLE + NBI + NBI-DF exhibited significantly higher accuracy compared to WLE (88.6% and 90.2% vs 74.2%, P < 0.01). For diminutive polyps, the DF mode significantly increased the rate of high-confidence optical diagnoses (89.1% vs 94.9%, P < 0.001). WLE + NBI + NBI-DF demonstrated high sensitivity (90.1%), specificity (95.5%), and negative predictive value (93.4%) in high-confidence predictions, enabling the implementation of the "diagnose-and-leave" strategy. This approach would have reduced 58.2% of unnecessary polypectomies without missing any advanced neoplastic lesions. Conclusion: NBI and DF modes provide accurate neoplastic predictions for rectosigmoid polyps. For diminutive polyps, DF magnification improves the confidence level of the optical diagnosis, allowing the safe implementation of the "diagnose-and-leave" strategy.

9.
Planta Med ; 90(5): 388-396, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490239

RESUMO

Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted by antidiabetic medication. Abrus precatorius is a medicinal plant with demonstrated antihyperglycaemic activity in animal models, but its mechanisms are unclear.This study evaluated the effect of a 50% ethanolic (v/v) A. precatorius leaf extract on (1) insulin-stimulated glucose uptake and (2) related gene expression in differentiated C2C12 myotubes using rosiglitazone as a positive control, and (3) generated a comprehensive phytochemical profile of A. precatorius leaf extract using liquid chromatography-high resolution mass spectrometry to elucidate its antidiabetic compounds. A. precatorius leaf extract significantly increased insulin-stimulated glucose uptake, and insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression; however, it had no effect on glucose transporter type 4 gene expression. At 250 µg/mL A. precatorius leaf extract, the increase in glucose uptake was significantly higher than 1 µM rosiglitazone. Fifty-five phytochemicals (primarily polyphenols, triterpenoids, saponins, and alkaloids) were putatively identified, including 24 that have not previously been reported from A. precatorius leaves. Abrusin, precatorin I, glycyrrhizin, hemiphloin, isohemiphloin, hispidulin 4'-O-ß-D-glucopyranoside, homoplantaginin, and cirsimaritin were putatively identified as known major compounds previously reported from A. precatorius leaf extract. A. precatorius leaves contain antidiabetic phytochemicals and enhance insulin-stimulated glucose uptake in myotubes via the protein kinase B/phosphoinositide 3-kinase pathway by regulating insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression. Therefore, A. precatorius leaves may improve skeletal muscle insulin sensitivity and hyperglycaemia. Additionally, it is a valuable source of bioactive phytochemicals with potential therapeutic use for diabetes.


Assuntos
Abrus , Diabetes Mellitus , Hiperglicemia , Resistência à Insulina , Animais , Insulina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Abrus/química , Proteínas Substratos do Receptor de Insulina/metabolismo , Rosiglitazona/metabolismo , Rosiglitazona/farmacologia , Transportador de Glucose Tipo 4 , Fosfatidilinositol 3-Quinases , Músculo Esquelético/metabolismo , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Glucose/farmacologia
10.
Cureus ; 16(2): e53545, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38445134

RESUMO

Background and objectives Achieving accurate real-time optical diagnoses of colorectal polyps with high-confidence predictions is crucial for appropriate decision-making in daily practice. The dual-focus (DF) magnification mode helps endoscopists scrutinize subtle features of polyp surfaces and vessel patterns. This prospective study aimed to evaluate the impact of DF imaging on enhancing the rate of high-confidence narrow-band imaging (NBI)-based optical diagnosis. Methods Consecutive adult patients who underwent colonoscopy and had small colorectal polyps (<10 mm) were enrolled between September 2022 and May 2023. The optical diagnosis of each polyp was evaluated during colonoscopy in two stages by the same endoscopist, utilizing NBI with DF magnification (NDB-DF). A confidence level was assigned to each prediction. High confidence was indicated by clinical judgment when a polyp exhibited distinctive features associated solely with one histological subtype and lacked characteristics of any other subtype. All procedures were carried out with a prototype 190 series Exera III NBI system (Olympus Corporation, Tokyo, Japan) with DF magnification. Results The study included 413 patients with 623 polyps, comprising 483 ≤ 5 mm and 140 measuring 6-9 mm. The majority were low-grade adenomas (343 lesions), with 17 identified as high-grade adenomas, and none characterized as deep submucosal invasive carcinomas. NBI-DF significantly improved the rate of high-confidence optical diagnoses compared to NBI for both ≤ 5 mm polyps (93.1% vs. 87.5%, p < 0.0001) and 6-9 mm polyps (97.9% vs. 94.2%, p = 0.03). Furthermore, DF significantly facilitated the assessment of microvessel and surface pattern criteria (p < 0.01). Conclusion DF magnification markedly enhanced the rate of high-confidence NBI-based optical predictions for small colorectal polyps. This technique demonstrates the potential for improving the diagnostic yield in real-time optical diagnosis of colorectal polyps in the Vietnamese setting.

11.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37822685

RESUMO

Entomopathogenic nematodes are commonly used to control insect pest populations in the field. They also contribute substantially to understanding the molecular basis of nematode pathogenicity and insect anti-nematode immunity. Here, we tested the effect of the entomopathogenic nematode Steinernema hermaphroditum on the survival and immune signaling regulation of Drosophila melanogaster wild type larvae. Our results indicate that S. hermaphroditum infective juveniles are pathogenic toward D. melanogaster larvae, but they fail to activate certain immune pathway readout genes. These findings imply that S. hermaphroditum employs mechanisms that allow these parasitic nematodes to interfere with the D. melanogaster immune system.

12.
Sci Rep ; 13(1): 17812, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857694

RESUMO

Although bioderived flame retardants are environmentally sustainable and less toxic, their impact on the thermal stability and flammability of polymers remains poorly understood. In this study, we assessed the influence of mycelium on the thermal stability and flame spread characteristics of epoxy through thermogravimetric analysis, Fourier transform infrared spectroscopy, the UL94 flammability test, and scanning electron microscopy. We observed a decrease in the maximum mass loss rate temperature when mycelium was incorporated into epoxy, indicating an earlier onset of thermal degradation. The inclusion of mycelium increased char yields above 418 °C due to mycelium's inherent char-forming ability. However, mycelium did not alter the thermal degradation pathway of epoxy. Furthermore, according to the UL94 test results, the incorporation of mycelium reduced the flame spread rate compared to that of neat epoxy. These findings contribute to our understanding of the interaction between bioderived flame retardants and polymers paving the way for the development of more sustainable fireproofing materials.

13.
Clin Endosc ; 56(4): 479-489, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37501625

RESUMO

BACKGROUND/AIMS: Accurate neoplastic prediction can significantly decrease costs associated with pathology and unnecessary colorectal polypectomies. Narrow band imaging (NBI) and dual-focus (DF) mode are promising emerging optical technologies for recognizing neoplastic features of colorectal polyps digitally. This study aimed to clarify the clinical usefulness of NBI with and without DF assistance in the neoplastic prediction of small colorectal polyps (<10 mm). METHODS: This cross-sectional study included 530 small colorectal polyps from 343 consecutive patients who underwent colonoscopy at the University Medical Center from September 2020 to May 2021. Each polyp was endoscopically diagnosed in three successive steps using white-light endoscopy (WLE), NBI, and NBI-DF and retrieved for histopathological assessment. The diagnostic accuracy of each modality was evaluated with reference to histopathology. RESULTS: There were 295 neoplastic polyps and 235 non-neoplastic polyps. The overall accuracies of WLE, WLE+NBI, and WLE+NBI+NBI-DF in the neoplastic prediction of colorectal polyps were 70.8%, 87.4%, and 90.8%, respectively (p<0.001). The accuracy of WLE+NBI+NBI-DF was significantly higher than that of WLE+NBI in the polyp size ≤5 mm subgroup (87.3% vs. 90.1%, p<0.001). CONCLUSION: NBI improved the real-time neoplastic prediction of small colorectal polyps. The DF mode was especially useful in polyps ≤5 mm in size.

14.
Nat Commun ; 14(1): 2929, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217466

RESUMO

Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design.


Assuntos
Infecções por HIV , Humanos , Antígenos HLA-B/genética , Linfócitos T Citotóxicos , Peptídeos , Epitopos de Linfócito T , Receptores de Antígenos de Linfócitos T
16.
Pharmaceuticals (Basel) ; 16(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36678596

RESUMO

Momordica cochinchinensis is a herbal medicine used throughout Asia and this study investigated the antimelanoma potentials and molecular mechanisms of M. cochinchinensis seed with emphasis on extraction to optimise bioactivity. Overall, the aqueous extract was superior, with a wider diversity and higher concentration of proteins and peptides that was more cytotoxic to the melanoma cells than other extraction solvents. The IC50 of the aqueous extract on melanoma cells were similar to treatment with current anticancer drugs, vemurafenib and cisplatin. This cytotoxicity was cancer-specific with lower cytotoxic effects on HaCaT epidermal keratinocytes. Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma.

17.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38233090

RESUMO

Immunologic recognition of peptide antigens bound to class I major histocompatibility complex (MHC) molecules is essential to both novel immunotherapeutic development and human health at large. Current methods for predicting antigen peptide immunogenicity rely primarily on simple sequence representations, which allow for some understanding of immunogenic features but provide inadequate consideration of the full scale of molecular mechanisms tied to peptide recognition. We here characterize contributions that unsupervised and supervised artificial intelligence (AI) methods can make toward understanding and predicting MHC(HLA-A2)-peptide complex immunogenicity when applied to large ensembles of molecular dynamics simulations. We first show that an unsupervised AI method allows us to identify subtle features that drive immunogenicity differences between a cancer neoantigen and its wild-type peptide counterpart. Next, we demonstrate that a supervised AI method for class I MHC(HLA-A2)-peptide complex classification significantly outperforms a sequence model on small datasets corrected for trivial sequence correlations. Furthermore, we show that both unsupervised and supervised approaches reveal determinants of immunogenicity based on time-dependent molecular fluctuations and anchor position dynamics outside the MHC binding groove. We discuss implications of these structural and dynamic immunogenicity correlates for the induction of T cell responses and therapeutic T cell receptor design.


Assuntos
Antígeno HLA-A2 , Simulação de Dinâmica Molecular , Humanos , Antígeno HLA-A2/metabolismo , Inteligência Artificial , Peptídeos/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Ligação Proteica
18.
Sci Rep ; 12(1): 15105, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068256

RESUMO

Mycelium fungal species exhibit fire retardant characteristics. The influence of the growth media on the fungal growth rates, biochemical composition, and microstructural characteristics and their relationship to thermal properties is poorly understood. In this paper, we demonstrate that molasses can support the growth of non-pathogenic Basidiomycota phylum fungal species producing bio-derived materials with potential fire retardation characteristics. Scanning electron microscopy and Fourier transform infrared (FTIR) spectrometry were used to interrogate the microstructural and biochemical properties of the molasses-grown mycelia species. Thermal decomposition of molasses-fed mycelia was evaluated via thermogravimetric analysis interfaced with FTIR for real-time evolved gas analysis. The morphological and microstructural characteristics of the residual char post-thermal exposure were also evaluated. The material characterization enabled the establishment of a relationship between the microstructural, biochemical properties, and thermal properties of molasses-fed mycelia. This paper presents a comprehensive exploration of the mechanisms governing the thermal degradation of three mycelial species grown in molasses. These research findings advance the knowledge of critical parameters controlling fungal growth rates and yields as well as how the microstructural and biochemical properties influence the thermal response of mycelia.


Assuntos
Basidiomycota , Incêndios , Meios de Cultura/metabolismo , Melaço , Micélio
19.
J Chem Inf Model ; 62(18): 4295-4299, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-36098536

RESUMO

Recent work showed that active site rather than full-protein-sequence information improves predictive performance in kinase-ligand binding affinity prediction. To refine the notion of an "active site", we here propose and compare multiple definitions. We report significant evidence that our novel definition is superior to previous definitions and better models of ATP-noncompetitive inhibitors. Moreover, we leverage the discontiguity of the active site sequence to motivate novel protein-sequence augmentation strategies and find that combining them further improves performance.


Assuntos
Trifosfato de Adenosina , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Ligantes , Ligação Proteica
20.
J Parasitol ; 108(4): 403-407, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36027574

RESUMO

The Baermann filter method is a long-standing, simple technique for recovering nematodes from soil and charcoal coprocultures. Material containing the nematodes is placed on a mesh screen lined with several layers of tissue paper or cheesecloth, and the screen is placed in the mouth of the funnel. Rubber tubing attached to the funnel stem is clamped, and water is added to submerge the material. The filtration material allows the nematodes to swim through while holding back the substrate. Over time the nematodes settle at the clamp in the tubing. After several hours, the clamp is opened and water containing the nematodes is collected. Although recovery of the nematodes is efficient, they are often contaminated with soil or charcoal debris, requiring a secondary cleaning by sedimentation or filtration. Described here is a small, simplified version of the Baermann apparatus that can be used as a secondary cleaning device. The "mini-Baermann" is constructed from materials commonly found in the laboratory. Experiments using infective larvae of 3 nematode species demonstrated that the majority of the larvae applied to the device are collected within 2 hr, and nearly all by 4 hr. Dead larvae fail to pass through the filter and do not significantly impact the passage of living larvae. In addition to removing debris from nematode suspensions, this device can rapidly and efficiently separate living, motile larvae from dead larvae.


Assuntos
Carvão Vegetal , Nematoides , Animais , Larva , Solo , Água
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