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1.
Nature ; 614(7947): 287-293, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36725928

RESUMEN

The ability of the ancient Egyptians to preserve the human body through embalming has not only fascinated people since antiquity, but also has always raised the question of how this outstanding chemical and ritual process was practically achieved. Here we integrate archaeological, philological and organic residue analyses, shedding new light on the practice and economy of embalming in ancient Egypt. We analysed the organic contents of 31 ceramic vessels recovered from a 26th Dynasty embalming workshop at Saqqara1,2. These vessels were labelled according to their content and/or use, enabling us to correlate organic substances with their Egyptian names and specific embalming practices. We identified specific mixtures of fragrant or antiseptic oils, tars and resins that were used to embalm the head and treat the wrappings using gas chromatography-mass spectrometry analyses. Our study of the Saqqara workshop extends interpretations from a micro-level analysis highlighting the socio-economic status of a tomb owner3-7 to macro-level interpretations of the society. The identification of non-local organic substances enables the reconstruction of trade networks that provided ancient Egyptian embalmers with the substances required for mummification. This extensive demand for foreign products promoted trade both within the Mediterranean8-10 (for example, Pistacia and conifer by-products) and with tropical forest regions (for example, dammar and elemi). Additionally, we show that at Saqqara, antiu and sefet-well known from ancient texts and usually translated as 'myrrh' or 'incense'11-13 and 'a sacred oil'13,14-refer to a coniferous oils-or-tars-based mixture and an unguent with plant additives, respectively.


Asunto(s)
Embalsamiento , Momias , Humanos , Antiguo Egipto , Embalsamiento/economía , Embalsamiento/historia , Embalsamiento/métodos , Cromatografía de Gases y Espectrometría de Masas , Historia Antigua , Momias/historia , Resinas de Plantas/análisis , Resinas de Plantas/historia , Cerámica/química , Cerámica/historia , Breas/análisis , Breas/historia , Aceites de Plantas/análisis , Aceites de Plantas/historia , Región Mediterránea , Clima Tropical , Bosques , Tracheophyta/química , Comercio/historia
2.
J Immunol ; 212(4): 737-747, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38169329

RESUMEN

Epigenetic regulation plays a crucial role in the development and progression of cancer, including the regulation of antitumor immunity. The reversible nature of epigenetic modifications offers potential therapeutic avenues for cancer treatment. In particular, histone deacetylase (HDAC) inhibitors (HDACis) have been shown to promote antitumor T cell immunity by regulating myeloid cell types, enhancing tumor Ag presentation, and increasing expression of chemokines. HDACis are currently being evaluated to determine whether they can increase the response rate of immune checkpoint inhibitors in cancer patients. Although the potential direct effect of HDACis on T cells likely impacts antitumor immunity, little is known about how HDAC inhibition alters the transcriptomic profile of T cells. In this article, we show that two clinical-stage HDACis profoundly impact gene expression and signaling networks in CD8+ and CD4+ T cells. Specifically, HDACis promoted T cell effector function by enhancing expression of TNF-α and IFN-γ and increasing CD8+ T cell cytotoxicity. Consistently, in a murine tumor model, HDACis led to enrichment of CD8+ T cell subsets with high expression of effector molecules (Prf1, Ifng, Gzmk, and Grmb) but also molecules associated with T cell exhaustion (Tox, Pdcd1, Lag3, and Havcr2). HDACis further generated a tumor microenvironment dominated by myeloid cells with immune suppressive signatures. These results indicate that HDACis directly and favorably augment T cell effector function but also increase their exhaustion signal in the tumor microenvironment, which may add a layer of complexity for achieving clinical benefit in combination with immune checkpoint inhibitors.


Asunto(s)
Inhibidores de Histona Desacetilasas , Neoplasias , Humanos , Animales , Ratones , Inhibidores de Histona Desacetilasas/farmacología , Epigénesis Genética , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Linfocitos T CD8-positivos , Expresión Génica , Microambiente Tumoral
3.
BMC Infect Dis ; 24(Suppl 1): 313, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486194

RESUMEN

INTRODUCTION: International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the "gold standard" treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM). METHOD: 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers' instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated. RESULTS: Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5-100), and the specificity was 99.4% (95% CI: 98.7-99.7). The ROC area values were 0.996 (95% CI: 0.992-0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1-99.2; NPV 99.9%, 95% CI: 99.5-100). CONCLUSIONS: The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.


Asunto(s)
Minorías Sexuales y de Género , Sífilis , Masculino , Humanos , Treponema pallidum , Homosexualidad Masculina , Anticuerpos Antibacterianos , Serodiagnóstico de la Sífilis/métodos , Pruebas Serológicas/métodos , Sensibilidad y Especificidad , Mediciones Luminiscentes/métodos , Aglutinación
4.
BMC Infect Dis ; 24(Suppl 1): 192, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38418941

RESUMEN

INTRODUCTION: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM). METHOD AND ANALYSES: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites. RESULTS: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs). CONCLUSIONS: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Sífilis , Masculino , Humanos , Sífilis/diagnóstico , Sífilis/epidemiología , Homosexualidad Masculina , Perú/epidemiología , Malta , Estudios Transversales , Treponema pallidum , Pruebas en el Punto de Atención , Serodiagnóstico de la Sífilis/métodos , Sensibilidad y Especificidad , Anticuerpos Antibacterianos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología
5.
Bioorg Chem ; 150: 107566, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38896936

RESUMEN

In the current study, novel pyrazolo[3,4-d]pyrimidine derivatives 5a-h were designed and synthesized as targeted anti-cancer agents through dual CDK2/GSK-3ß inhibition. The designed compounds demonstrated moderate to potent activity on the evaluated cancer cell lines (MCF-7 and T-47D). Compounds 5c and 5 g showed the most promising cytotoxic activity against the tested cell lines surpassing that of the used reference standard; staurosporine. On the other hand, both compounds showed good safety and tolerability on normal fibroblast cell line (MCR5). The final compounds 5c and 5 g showed a promising dual CDK2/GSK-3ß inhibitory activity with IC50 of 0.244 and 0.128 µM, respectively, against CDK2, and IC50 of 0.317 and 0.160 µM, respectively, against GSK-3ß. Investigating the effect of compounds 5c and 5 g on CDK2 and GSK-3ß downstream cascades showed that they reduced the relative cellular content of phosphorylated RB1 and ß-catenin compared to that in the untreated MCF-7 cells. Moreover, compounds 5c and 5 g showed a reasonable selective inhibition against the target kinases CDK2/GSK-3ß in comparison to a set of seven off-target kinases. Furthermore, the most potent compound 5 g caused cell cycle arrest at the S phase in MCF-7 cells preventing the cells' progression to G2/M phase inducing cell apoptosis. Molecular docking studies showed that the final pyrazolo[3,4-d]pyrimidine derivatives have analogous binding modes in the target kinases interacting with the hinge region key amino acids. Molecular dynamics simulations confirmed the predicted binding mode by molecular docking. Moreover, in silico predictions indicated their favorable physicochemical and pharmacokinetic properties in addition to their promising cytotoxic activity.

6.
Med Sci Monit ; 30: e944110, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38685688

RESUMEN

BACKGROUND A luting agent is a dental cement used to secure a dental restoration. This study aimed to evaluate retentive strength of 50 endodontically-treated single-rooted mandibular second premolars (extracted) restored using 5 common luting (cement) agents. MATERIAL AND METHODS Fifty single-rooted mandibular second premolars with adequate root length and uniform size/shape were decoronated. After completing endodontic biomechanical preparation and obturation, root canals of all specimens were prepared to receive a cast post core. Depending upon cementation type, CPC specimens were divided in 5 groups (10 each) (Gp): Zinc phosphate (Gp ZP), polycarboxylate (Gp PC), glass ionomer (Gp GI), resin-modified glass ionomer (Gp RGI), and resin cement (Gp RC). Retentive strength was determined using the adhesive failure pull-out test. Mean/standard deviations were calculated for tensile forces (in kilograms) and differences were determined using analysis of variance (ANOVA). Multiple comparison was performed using the t test. A P value of ≤0.05 indicated a statistically significant difference. RESULTS The order of mean tensile strength from higher to lower was Gp RC (21.46) >Gp RGI (18.17) >Gp GI (16.07) >Gp ZP (15.33) >Gp PC (13.63). Differences in retentive strengths between the cements were significant (P≤0.05). Multiple-group comparisons showed that except for Gp ZP and Gp GI, all groups differed significantly from each other. CONCLUSIONS All investigated cements provided optimal retentive strengths, with wide differences between them. Resin cements should be used when CPC removal is not anticipated, while polycarboxylate or zinc phosphate should be used if CPC removal is anticipated.


Asunto(s)
Diente Premolar , Cementos Dentales , Humanos , Mandíbula , Técnica de Perno Muñón , Cementos de Ionómero Vítreo , Cementos de Resina , Resistencia a la Tracción , Ensayo de Materiales/métodos , Restauración Dental Permanente/métodos , Raíz del Diente/efectos de los fármacos , Cemento de Fosfato de Zinc
7.
Med Sci Monit ; 30: e944175, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38773745

RESUMEN

BACKGROUND Effective communication and patient education are important in geriatric dental care. Memory decline complicates patient adherence. This study aimed to compare verbal, audio, and video patient education material (PEM) and adherence to dental prosthetic management in edentulous patients. MATERIAL AND METHODS 90 completely/partially edentulous patients (aged 40 to 70 years), were divided (simple random) into three groups (Gp) of 30 each . A total of 68 instructions were organized into 9 learning categories. For GpVi, a 20 minute video was shot using a Sony camera (PD170), with two actors depicting related PEM information. Patients were recalled after 1 day and 7days, to recall the PEM instructions. A Denture plaque Index (DPI) determined the efficiency of the instructions at both time intervals. Frequencies, means and standard deviations were derived for each group and then compared using Chi square, paired and unpaired t test and a Neuman-Keul post hoc pairwise test. All significant differences were kept at probability t value of ≤0.05. RESULTS PEM instructions related to patient individuality, proper tongue position and miscellaneous showed poor patient recall. At 1 day interval, audio was found to have better recall than video and verbal in 5 PEM instruction categories. At 7 day interval, video showed better recall than other two groups (P≤0.05). Despite improvements in patients recall, DPI revealed better denture hygiene maintenance in patients receiving instructions through video format (P≤0.05). CONCLUSIONS For all categories, no single media was considered to be sufficient, audio produced early better recall while video influenced long term recall and better denture hygiene maintenance.


Asunto(s)
Dentaduras , Boca Edéntula , Higiene Bucal , Educación del Paciente como Asunto , Humanos , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Femenino , Masculino , Anciano , Higiene Bucal/métodos , Higiene Bucal/educación , Adulto , Cumplimiento y Adherencia al Tratamiento , Cooperación del Paciente
8.
Graefes Arch Clin Exp Ophthalmol ; 262(5): 1489-1498, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38141059

RESUMEN

PURPOSE: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months. METHODS: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-naïve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed. RESULTS: Mean BCVA (in logMAR) was 0.60 ± 0.47, 0.45 ± 0.41, 0.49 ± 0.49, 0.61 ± 0.54, 0.59 ± 0.56, and 0.67 ± 0.57 at baseline, 3, 6, 12, 18, and 24 months respectively. Overall, BCVA showed minimal worsening of 0.07 ± 0.54 logMAR (p = 0.07). 13.38 ± 3.77 anti-VEGF injections were given through 24 months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p = 0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p = 0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p = 0.06). BCVA was negatively correlated with PEDCI-F (r = -0.28, p < 0.01), and positively correlated with PEDCI-N (r = 0.28, p < 0.01) and PEDCI-S (r = 0.15, p = 0.03). CONCLUSION: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs.


Asunto(s)
Degeneración Macular , Desprendimiento de Retina , Degeneración Macular Húmeda , Humanos , Preescolar , Inhibidores de la Angiogénesis/uso terapéutico , Ranibizumab/uso terapéutico , Estudios Retrospectivos , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/tratamiento farmacológico , Tomografía de Coherencia Óptica , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Inyecciones Intravítreas , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológico
9.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34663733

RESUMEN

We demonstrate how programmable shape evolution and deformation can be induced in plant-based natural materials through standard digital printing technologies. With nonallergenic pollen paper as the substrate material, we show how specific geometrical features and architectures can be custom designed through digital printing of patterns to modulate hygrophobicity, geometry, and complex shapes. These autonomously hygromorphing configurations can be "frozen" by postprocessing coatings to meet the needs of a wide spectrum of uses and applications. Through computational simulations involving the finite element method and accompanying experiments, we develop quantitative insights and a general framework for creating complex shapes in eco-friendly natural materials with potential sustainable applications for scalable manufacturing.


Asunto(s)
Papel , Tecnología , Simulación por Computador
10.
J Immunoassay Immunochem ; 45(2): 93-111, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38174954

RESUMEN

Hashimoto's thyroiditis (HT) and Graves' disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto's thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves' disease.


Asunto(s)
Enfermedades Autoinmunes , Enfermedad de Graves , Enfermedad de Hashimoto , Humanos , Egipto , Predisposición Genética a la Enfermedad/genética , Enfermedad de Graves/genética , Enfermedad de Graves/patología , Enfermedad de Hashimoto/genética , Polimorfismo de Nucleótido Simple/genética , Receptor Toll-Like 7/genética , Factor de Necrosis Tumoral alfa/genética
11.
J Gene Med ; 25(9): e3532, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37209019

RESUMEN

BACKGROUND: COVID-19 is a novel infectious disease for which no specific treatment exists. It is likely that a combination of genetic and non-genetic factors predispose to it. Expression levels of genes that are involved in the interaction with SARS-CoV-2 or the host response are thought to play a role in disease susceptibility and severity. It is crucial to explore biomarkers for disease severity and outcome. Herein, we studied the expression levels and effects of long non-coding metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) and long non-coding maternally expressed gene 3 (lnc-MEG3) in COVID-19 patients. The study enrolled 35 hospitalized and 35 non-hospitalized COVID-19 patients, and 35 healthy controls. A chest computed tomography (CT) scan, complete blood count (CBC), ferritin, C-reactive protein (CRP), D-dimer and analysis of lnc-MALAT1 and lnc-MEG3 expression were done. RESULTS: There was a significant relation between ferritin, CRP, D-dimer levels, oxygen saturation, CT-CORADS score and disease severity. Lnc-MALAT1 was significantly higher but lnc-MEG3 was significantly lower in patients vs. controls, and in hospitalized vs. non-hospitalized patients. Elevated MALAT1 and reduced MEG3 levels were significantly associated with more elevated ferritin, CRP, D-dimer levels, lower oxygen saturation, higher CT-CORADS score and poor survival. Moreover, MALAT1 and MEG3 levels displayed higher sensitivity and specificity as predictors of COVID-19 severity compared with other prognostic biochemical markers such as ferritin, CRP, and D-dimer. CONCLUSIONS: MALAT1 levels are higher, whereas MEG3 levels are lower in COVID-19 patients. Both are linked to disease severity and mortality and could emerge as predictive biomarkers for COVID-19 severity and therapeutic targets.


Asunto(s)
COVID-19 , ARN Largo no Codificante , Humanos , COVID-19/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Biomarcadores , Ferritinas
12.
Mol Divers ; 27(4): 1645-1660, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36042119

RESUMEN

The involvement of Trypanosoma congolense sialidase alongside phospholipase A2 has been widely accepted as the major contributing factor to anemia during African animal trypanosomiasis. The enzymes aid the parasite in scavenging sialic acid and fatty acids necessary for survival in the infected host, but there are no specific drug candidates against the two enzymes. This study investigated the inhibitory effects of ß-sitosterol on the partially purified T. congolense sialidase and phospholipase A2. Purification of the enzymes using DEAE cellulose column led to fractions with highest specific activities of 8016.41 and 39.26 µmol/min/mg for sialidase and phospholipase A2, respectively. Inhibition kinetics studies showed that ß-sitosterol is non-competitive and an uncompetitive inhibitor of sialidase and phospholipase A2 with inhibition binding constants of 0.368 and 0.549 µM, respectively. Molecular docking of the compound revealed binding energies of - 8.0 and - 8.6 kcal/mol against the sialidase and phospholipase A2, respectively. Furthermore, 100 ns molecular dynamics simulation using GROMACS revealed stable interaction of ß-sitosterol with both enzymes. Hydrogen bond interactions between the ligand and Glu284 and Leu102 residues of the sialidase and phospholipase A2, respectively, were found to be the major stabilizing forces. In conclusion, ß-sitosterol could serve as a dual inhibitor of T. congolense sialidase and phospholipase A2; hence, the compound could be exploited further in the search for newer trypanocides.


Asunto(s)
Trypanosoma congolense , Tripanosomiasis Africana , Animales , Simulación de Dinámica Molecular , Neuraminidasa/química , Trypanosoma congolense/metabolismo , Simulación del Acoplamiento Molecular , Cinética , Tripanosomiasis Africana/tratamiento farmacológico , Tripanosomiasis Africana/veterinaria , Fosfolipasas/metabolismo , Fosfolipasas/farmacología
13.
Med Sci Monit ; 29: e939225, 2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36772790

RESUMEN

BACKGROUND The purpose of the study was to evaluate the influence of dental implant placement at different bone levels upon the resultant postoperative peri-implant bone loss. MATERIAL AND METHODS Forty-two partially edentulous patients seeking implant-supported single-crown restorations were screened followed by segregation into 2 groups (GP), GP E (equicrestal) and GP S (subcrestal) (n=21 each). Sixty endosseous implants (30 each) (Adin Tourage-S, Israel), size 3.5/8 and 4/10 mm for mandibles, were placed using a 2-stage surgical procedure. At 4 to 6 months, straight abutments were attached followed by restoration (Vita Zahnfabrik, Germany). Crestal bone levels (mesial/distal) of implant fixtures were assessed at 5 time intervals (after surgery, and at 3, 6, 9, and 12 months) using digital radiography. Means and standard deviations were calculated, following which the differences were statistically analyzed using ANOVA at P value of <0.05. RESULTS The mean annual bone loss for GP S (1.96 mm) was higher than GP E (1.10 mm). At all studied time intervals, the bone loss for implants in GP S was higher than in GP E (P<0.05). Between time intervals, lowest bone loss was observed on the distal side in GP E (0.11 mm/6-9 month) and the highest bone loss was observed on the distal side of GP S (0.6 mm/9-12 month). Differences in the means between the 2 groups on mesial and distal sides were statistically significant at all time intervals (P<0.05). CONCLUSIONS Subcrestal implant placement was associated with more bone loss than when implants are placed at the crestal level.


Asunto(s)
Pérdida de Hueso Alveolar , Enfermedades Óseas Metabólicas , Implantes Dentales , Humanos , Prótesis e Implantes , Mandíbula/cirugía , Biometría , Coronas
14.
Med Sci Monit ; 29: e940098, 2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37183802

RESUMEN

BACKGROUND The present study aimed to compare the clinical performance and gingival sulcus width changes in partially edentulous patients using cotton and polymer gingival retraction cords. MATERIAL AND METHODS Fifty partially edentulous patients were divided into 2 groups (Gp C and Gp P) and were subjected to single crown/fixed partial denture treatment. Clinical parameters, including plaque index scores, placement time, and hemorrhage control scores, were assessed. Gingival sulcus width changes before and after retraction were evaluated using individual type 4 dental stone dies observed under an optical microscope. Statistical analysis was performed using dependent/independent t tests. RESULTS The mean placement time, hemorrhage control time, and hemorrhagic scores were lower in Gp P than in Gp C, indicating better clinical performance of polymer-based retraction cord. Both groups showed an increase in sulcus width after retraction, but Gp P had a significantly higher sulcus width (690.03±45.37) compared to Gp C (471.38±28.13). The mean difference in sulcus width between baseline and after retraction was also significantly higher in Gp P (525.84 micrometers) than in Gp C (309.11 micrometers). CONCLUSIONS The present study shows that polymer-based cords produce more sulcus width and have better clinical performance compared to cotton-based gingival retraction cords. These results suggest that the use of polymer-based retraction cords can improve the quality of dental impressions in partially edentulous patients.


Asunto(s)
Encía , Polímeros , Humanos , Coronas , Hemorragia
15.
BMC Public Health ; 23(1): 1805, 2023 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-37716999

RESUMEN

BACKGROUND: A direct consequence of global warming, and strongly correlated with poor physical and mental health, food insecurity is a rising global concern associated with low dietary intake. The Coronavirus pandemic has further aggravated food insecurity among vulnerable communities, and thus has sparked the global conversation of equal food access, food distribution, and improvement of food support programs. This research was designed to identify the key features associated with food insecurity during the COVID-19 pandemic using Machine learning techniques. Seven machine learning algorithms were used in the model, which used a dataset of 32 features. The model was designed to predict food insecurity across ten Arab countries in the Gulf and Mediterranean regions. A total of 13,443 participants were extracted from the international Corona Cooking Survey conducted by 38 different countries during the COVID -19 pandemic. RESULTS: The findings indicate that Jordanian, Palestinian, Lebanese, and Saudi Arabian respondents reported the highest rates of food insecurity in the region (15.4%, 13.7%, 13.7% and 11.3% respectively). On the other hand, Oman and Bahrain reported the lowest rates (5.4% and 5.5% respectively). Our model obtained accuracy levels of 70%-82% in all algorithms. Gradient Boosting and Random Forest techniques had the highest performance levels in predicting food insecurity (82% and 80% respectively). Place of residence, age, financial instability, difficulties in accessing food, and depression were found to be the most relevant features associated with food insecurity. CONCLUSIONS: The ML algorithms seem to be an effective method in early detection and prediction of food insecurity and can profoundly aid policymaking. The integration of ML approaches in public health strategies could potentially improve the development of targeted and effective interventions to combat food insecurity in these regions and globally.


Asunto(s)
COVID-19 , Adulto , Humanos , COVID-19/epidemiología , Pandemias , Árabes , Arabia Saudita , Factores de Riesgo , Aprendizaje Automático
16.
Parasitol Res ; 122(12): 2751-2772, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37851179

RESUMEN

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.


Asunto(s)
Plantas Medicinales , Esquistosomiasis Urinaria , Esquistosomiasis , Animales , Humanos , Nigeria/epidemiología , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Schistosoma haematobium , Extractos Vegetales , Biomarcadores , Esquistosomiasis Urinaria/parasitología
17.
Chem Biodivers ; 20(2): e202200909, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36565063

RESUMEN

The dipeptidyl peptidase-IV (DPP-IV) inhibitory activity of Khaya senegalensis extracts was evaluated. The DPP-IV from a rat kidney was purified to a purification fold of 2.3. Among extracts from K. senegalensis, the hexane extract had the best DPP-IV inhibitory activity, with IC50 value of 1.56±0.61 µg/mL and was fractionated to eleven fractions (A-K). Fraction I had the best DPP-IV inhibition via uncompetitive pattern. GC-MS analysis of fraction I showed that the major bioactive compounds were 3-amino-3-hydroxyimino-N-phenylpropanamide (1) and 11-(2-cyclopenten-1-yl)undecanoic acid (2), with good binding affinities toward DPP-IV, based on molecular docking,. They were then subjected to molecular dynamic simulation using WEBGRO and utilizing a GROMACS system for 100 ns. The 3-amino-3-hydroxyimino-N-phenylpropanamide-DPP-IV complex was more stable and compact than the other complex. K. senegalensis contains compounds like 1 that might be used for the design of new DPP-IV inhibitors.


Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV , Simulación de Dinámica Molecular , Simulación del Acoplamiento Molecular , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología
18.
Foodborne Pathog Dis ; 20(8): 315-333, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37389828

RESUMEN

The objective of this study was to conduct a systematic review to comprehensively understand antimicrobial resistance (AMR) in Listeria monocytogenes (LM) isolated from meat and meat products. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Published articles from 2000 to 2022 were collected from six widely used online databases, including AGRICOLA, PubMed, Web of Science (WoS), Scopus, Cochrane Library, and CINAHL-EBSCO. Prevalence rates and AMR of pathogen isolates were analyzed using MedCalc software, including the I2 statistic and Cochrane Q test for heterogeneity. Sensitivity analysis, subgroup analysis, and meta-regression were conducted to analyze potential sources of heterogeneity at a 95% significance level. The distribution and prevalence of multidrug resistance (MDR) were examined using a random-effect model. The pooled frequency of bacterial MDR was 22.97% (95% confidence interval [CI] = 14.95-32.13). The studies exhibited high heterogeneity (I2 = 94.82%, 95% CI = 93.74-95.71, p < 0.0001). Furthermore, the most prevalent antibiotics resistance found in the majority of included studies were tetracycline, clindamycin, penicillin, ampicillin, and oxacillin (I2 = 86.66%, 95% CI = 73.20-93.36, p < 0.0001). This meta-analysis provides a comprehensive understanding of AMR in LM isolates, and the results indicate that none of the variable factors, including sampling location, sampling size, or methodology, significantly influenced the outcome of LM isolates resistant to multidrug.


Asunto(s)
Listeria monocytogenes , Productos de la Carne , Productos de la Carne/microbiología , Antibacterianos/farmacología , Carne/microbiología , Ampicilina/farmacología , Pruebas de Sensibilidad Microbiana , Prevalencia , Farmacorresistencia Bacteriana
19.
AAPS PharmSciTech ; 24(1): 44, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36703092

RESUMEN

Tenoxicam (TX) is a non-steroidal anti-inflammatory agent that can be used to control pain in various ophthalmic lesions like cataracts, refractive surgery, and corneal abrasion. TX has a very slightly aqueous solubility of 0.072 mg/mL resulting in difficulty to be formulated in ophthalmic solutions. This study aims to improve TX solubility by converting it into its potassium salt to achieve a target of 10 mg/mL (1%w/v) concentration of TX in the desired aqueous medium for the formulation of aqueous ophthalmic solutions. The synthesized TX salt was characterized by different evaluation parameters such as solubility studies, 1H NMR, IR, and elemental analyses. Different TX potassium solutions were formulated at concentrations of 0.5% and 1% w/v using different viscosity-imparting agents. The prepared solutions were characterized for their physicochemical properties including visual inspection, pH, rheological, in vitro release, and kinetic behavior. Also, the formulations were biologically evaluated in vivo using male albino rabbits. The obtained results showed the successful synthesis of TX salt, as indicated by IR and NMR, and elemental analysis. The solubility study showed that the solubility of TX was improved hugely to 18 mg/mL (250-fold). In addition, the results showed that the prepared formulations showed acceptable physicochemical properties. The highest release rate was obtained with formula F1, which contains no viscosity-imparting agents. While as, the lowest release rate was obtained in the case of formula F9, composed of Pluronic F127 (12% w/v). The in vivo results showed that TX optimized ophthalmic solutions F8 and F9 inhibited the redness and edema in an extended or sustained manner.


Asunto(s)
Sistemas de Liberación de Medicamentos , Piroxicam , Animales , Masculino , Conejos , Sistemas de Liberación de Medicamentos/métodos , Antiinflamatorios no Esteroideos , Soluciones Oftálmicas
20.
Pharmacol Res ; 179: 106158, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35272043

RESUMEN

Diterpenes are a diverse group of structurally complex natural products with a wide spectrum of biological activities, including antidiabetic potential. In the last 25 years, numerous diterpenes have been investigated for antidiabetic activity, with some of them reaching the stage of clinical trials. However, these studies have not been comprehensively reviewed in any previous publication. Herein, we critically discussed the literature on the potential of diterpenes as antidiabetic agents, published from 1995 to September, 2021. In the period under review, 427 diterpenes were reported to have varying degrees of antidiabetic activity. Steviol glycosides, stevioside (1) and rebaudioside A (2), were the most investigated diterpenes with promising antidiabetic property using in vitro and in vivo models, as well as human subjects. All the tested pimaranes consistently showed good activity in preclinical evaluations against diabetes. Inhibitions of α-glucosidase and protein tyrosine phosphatase 1B (PTP 1B) activities and peroxisome proliferator-activated receptors gamma (PPAR-γ) agonistic property, were the most frequently used models for studying the antidiabetic activity of diterpenes. The molecular mechanisms of action of the diterpenes include increased GLUT4 translocation, and activation of phosphoinositide 3-kinase (PI3K) and AMP-activated protein kinase (AMPK)-dependent signaling pathways. This review revealed that diterpenes hold promising antidiabetic potential while stevioside (1) and rebaudioside A (2) are the only diterpenes that were advanced to the clinical trial stage of the drug discovery pipeline. Diterpenes belonging to the abietane, labdane, pimarane and kaurane classes have shown promising activity in in vitro and in vivo models of diabetes and should be further investigated.


Asunto(s)
Diabetes Mellitus , Diterpenos de Tipo Kaurano , Diterpenos , Proteínas Quinasas Activadas por AMP , Diabetes Mellitus/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/uso terapéutico , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fosfatidilinositol 3-Quinasas
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