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Nucleic Acid Therapeutics Jul 2024Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an...
Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with -positive tumors.
PubMed: 38957973
DOI: 10.1089/nat.2024.0005 -
Surgical Infections Jul 2024The prophylactic use of antibiotics in parotid region surgery continues to be a subject of debate. The aim of this study is to elucidate the impact of antibiotic...
The prophylactic use of antibiotics in parotid region surgery continues to be a subject of debate. The aim of this study is to elucidate the impact of antibiotic prophylaxis on surgical site infections (SSIs) in parotid region surgery. Patients who received antibiotic prophylaxis during the peri-operative period were designated as group 1, whereas those who did not were categorized into group 2. Group 1 cases were further subdivided into three subgroups based on different antibiotic usage patterns. Patient individual information was collected. Clinical data such as surgical duration, post-operative hospital stay, incision infection status, and antibiotic usage were recorded. All data were compared and analyzed among different groups. A total of 357 patients were included in the study, with no statistically significant differences in baseline characteristics. Pre-operative American Society of Anesthesiologists scores did not significantly differ between groups (p = 0.151), but there was a significant distinction in National Nosocomial Infection Surveillance (NNIS) index values (p = 0.044). Furthermore, surgical duration (p = 0.001) and pathology types (p = 0.016) differed significantly. The post-operative hospital stay in group 1 was longer than that in group 2 (p < 0.01). The post-operative SSI rate in group 1 was lower than that in group 2 without statistical significance (2.55% vs. 5.59%, p = 0.141). The logistic regression analysis showed that malignant tumors, longer surgical durations, and higher NNIS index scores correlated positively with post-operative SSI rates. Meanwhile, compared with non-use, all three different antibiotic use modes correlated negatively with SSI occurrence. Antibiotic prophylaxis in parotid gland surgery shows no significant reduction in SSI occurrence. If there is a compelling reason to administer prophylactic antibiotics, pre-operative single dose may be a relatively feasible measure for preventing SSIs.
PubMed: 38957972
DOI: 10.1089/sur.2024.054 -
Journal of the Science of Food and... Jul 2024The transesterification of butteroil has been shown to alter its lipid chemistry and thus alter the crystallization of the fat. The reaction kinetics and resulting...
BACKGROUND
The transesterification of butteroil has been shown to alter its lipid chemistry and thus alter the crystallization of the fat. The reaction kinetics and resulting crystallization of the butteroil differ depending on the nature of the catalyst used. Modeling the reaction with vegetable oils is a simpler method for the analysis of resulting products to understand the chemical and physiochemical changes that occur based on catalyst selection. The objective of this work is to perform a chemical transesterification of coconut and corn oil using monovalent and divalent catalysts to investigate the chemical and crystal changes that occur.
RESULTS
Coconut and corn oil were subjected to chemical transesterification using both Ca(OH) and KOH as catalysts. In both the coconut and corn oil samples, transesterification caused monoglycerides (MAGs) and diacylglycerides (DAGs) to form from the most abundant fatty acid found in each sample. Coconut oil's melting temperature, solid fat content (SFC), and storage modulus decreased as a result of the transesterification, and crystals began to form in the corn oil causing melting thermograms to be evident, higher SFC, and a more viscous oil as a result. Using Ca(OH) as a catalyst resulted in more MAG formation, and a higher SFC and melting temperature than when KOH was used as a catalyst.
CONCLUSION
The results demonstrate that the chemical changes that result from transesterification of plant-based oils change the crystallization behavior of the oils and can therefore be used for different applications in the food industry. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
PubMed: 38957971
DOI: 10.1002/jsfa.13706 -
AIDS Patient Care and STDs Jul 2024To understand the global dual HIV infection (DI) profiles comprehensively, the databases Cochrane Library, Embase, PubMed, and Web of Science were the data sources up to... (Review)
Review
To understand the global dual HIV infection (DI) profiles comprehensively, the databases Cochrane Library, Embase, PubMed, and Web of Science were the data sources up to March 31, 2024 (PROSPERO: CRD42023388328). Stata and R-language software were used to analyze the extracted data. Publication bias was assessed using Egger's test. Sensitivity analysis was conducted to evaluate the stability of the combined effect values. Data from 17 eligible studies across four continents (Africa, Asia, Europe, and North America) with 1,475 subjects were used. The combined dual infection rate (DIR) was 10.47% (95% CI: 7.11%-14.38%) without a time trend ( = 0.105). The DIRs of target population groups differed significantly, with FSWs having the highest DIR (15.14%), followed by general population (12.08%), MSM (11.84%), and DUs (9.76%). The subtype profiles of 122 patients with dual infection were extracted, and the results showed that intrasubtype infections were predominant in coinfection (16/22, 72.73%) and superinfection (68/100, 68.00%) groups, with the subtype pattern B and B accounts for the largest proportion. The global dual infection rate may be underestimated, even though the data fluctuated around 10% and showed no time trend. The occurrence of DI indicated that individuals still do not acquire sufficient resistance to HIV even after primary infection, which could potentially compromise the patient's treatment effect and lead to the emergence of new subtypes, posing a significant challenge to HIV prevention, control, and treatment, suggesting that behavioral counseling and health education for all HIV-infected individuals are still crucial during the antiviral therapy.
PubMed: 38957963
DOI: 10.1089/apc.2024.0100 -
Journal of Chemical Theory and... Jul 2024Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into...
Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into biological function. The present work describes an extensive set of backbone NH and side-chain methyl group generalized order parameters for the ribonuclease HI (RNH) enzyme derived from 2-μs microsecond MD simulations using the OPLS4 and AMBER-FF19SB force fields. The simulated generalized order parameters are compared with values derived from NMR N and CHD spin relaxation measurements. The squares of the generalized order parameters, for the N-H bond vector and for the methyl group symmetry axis, characterize the equilibrium distribution of vector orientations in a molecular frame of reference. Optimal agreement between simulated and experimental results was obtained by averaging or calculated by dividing the simulated trajectories into 50 ns blocks (∼five times the rotational diffusion correlation time for RNH). With this procedure, the median absolute deviations (MAD) between experimental and simulated values of and are 0.030 (NH) and 0.061 (CH) for OPLS4 and 0.041 (NH) and 0.078 (CH) for AMBER-FF19SB. The MAD between OPLS4 and AMBER-FF19SB are 0.021 (NH) and 0.072 (CH). The generalized order parameters for the methyl group symmetry axis can be decomposed into contributions from backbone fluctuations, between-rotamer dihedral angle transitions, and within-rotamer dihedral angle fluctuations. Analysis of the simulation trajectories shows that () backbone and side chain conformational fluctuations exhibit little correlation and that () fluctuations within rotamers are limited and highly uniform with values that depend on the number of dihedral angles considered. Low values of , indicative of enhanced side-chain flexibility, result from between-rotamer transitions that can be enhanced by increased local backbone flexibility.
PubMed: 38957960
DOI: 10.1021/acs.jctc.4c00378 -
Surgical Infections Jul 2024Necrotizing fasciitis (NF) and sepsis shock (SS) are both severe and life-threatening conditions requiring specialized care, including palliative care (PC), to optimize...
Gender and Racial Differences in the Provision of Palliative Care Services Among Critically ill Necrotizing Fasciitis and Septic Shock Geriatric Patients: Analysis of a Nationwide Database in the United States.
Necrotizing fasciitis (NF) and sepsis shock (SS) are both severe and life-threatening conditions requiring specialized care, including palliative care (PC), to optimize comfort. However, data on the utilization of PC in this population, including racial and gender differences, are limited. We used the National Inpatient Sample (NIS) database from 2016 to 2020 to extract data on patients with NF and SS as well as PC utilization. Chi-squared tests and multivariate linear regression models were utilized to analyze relationships between categorical and continuous variables, respectively. Multivariable logistic regression was used to determine adjusted odds ratios (aORs) and 95% confidence intervals (CI) for various outcomes among various gender and racial groups. Mann-Kendall trend test was used to assess mortality trends over time. Among the 11,260 patients with NF and SS, 2,645 received PC whereas 8,615 did not. Female patients had significantly higher odds of receiving PC versus males (aOR: 1.42, 95% CI 1.27-1.58). No significant racial differences in PC utilization were observed. Patients receiving PC had higher odds of in-hospital mortality (aOR: 1.18, 95% CI 1.03-1.35). No significant trend in in-hospital deaths was observed over the study period. PC was associated with significantly shorter length-of-stay and lower costs. Our study provides comprehensive insights, and identifies gender differences in PC utilization in NF and SS patients. Further research must aim to refine delivery strategies and address potential differences in PC.
PubMed: 38957958
DOI: 10.1089/sur.2024.029 -
A Snake Venom Peptide and Its Derivatives Prevent Aβ Aggregation and Eliminate Toxic Aβ Aggregates .ACS Chemical Neuroscience Jul 2024Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its...
Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-β (Aβ) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system. In this study, nine peptide derivatives of Crotamine, a polypeptide from Rattlesnake venom, as well as one d-enantiomer, were evaluated for their ability to modulate Aβ aggregation through various assays such as ThT, QIAD, SPR, and sFIDA. All tested peptides were able to decrease Aβ aggregation and eliminate Aβ aggregates. Additionally, all of the peptides showed an affinity for Aβ. This study is the first to describe the potential of crotamine derivative peptides against Aβ aggregation and to identify a promising d-peptide that could be used as an effective pharmacological tool against AD in the future.
PubMed: 38957957
DOI: 10.1021/acschemneuro.4c00089 -
The Journal of Physical Chemistry. A Jul 2024Of late, siloxane-containing vitrimers have gained significant interest due to their fast dynamic characteristics over a reasonable temperature range (180-220 °C),...
Of late, siloxane-containing vitrimers have gained significant interest due to their fast dynamic characteristics over a reasonable temperature range (180-220 °C), making them well-suited for diverse applications. The exchange reaction pathway in the siloxane vitrimers is accountable for the covalent adaptive network, with the reaction's effectiveness being regulated by either organic or organometallic catalysts. However, directly studying the exchange reaction pathway in the bulk phase using experimental approaches is challenging because of the intricate and interconnected structure of these vitrimers. Here, we perform comprehensive density functional theory (DFT) and experimental investigations to discover the detailed catalytic efficacy of siloxane exchange and provide direction for the reaction process using a 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyst. The calculated transition barrier energy and catalytic efficiency of hexamethyldisiloxane and dihydroxy-dimethylsilane exchange derived from the nudged elastic band with transition-state calculations strongly agree with the experimental findings. In addition, Fukui indices, along with partial charges, are employed to evaluate the nucleophilic and electrophilic behaviors of silanol and siloxane molecules. Our analysis revealed that by utilizing the Fukui indices of both the acid and the base, we can make an approximate estimation of the respective kinetics of the S2 process in the siloxane exchange reaction mechanism. These findings establish a foundation for comprehending a crucial aspect of the exchange mechanism in siloxane vitrimer systems and could aid in the development of novel catalysts.
PubMed: 38957945
DOI: 10.1021/acs.jpca.4c01394 -
The Journal of Asthma : Official... Jul 2024Asthma is a chronic inflammatory disease of the lower airways that affects more than 260 million people worldwide and has been related to more than 460,000 deaths a...
Asthma is a chronic inflammatory disease of the lower airways that affects more than 260 million people worldwide and has been related to more than 460,000 deaths a year. It is estimated that in 60% of asthma cases, the symptoms are not adequately controlled. The objective of this study was to determine the association between some comorbidities, habits, and health risk behaviors with uncontrolled asthma in a sample of young people with asthma. Through a cross-sectional study, data from 1,078 young people aged 17 to 19 years were analysed. Information was collected through physical examination, direct questioning, and the application of a self-administered questionnaire. In the group of young people with asthma, the prevalence of uncontrolled asthma was 20.6%, of which 53.8% were women, 76.9% suffered from rhinitis, 46.2% were overweight and 23.1% were obese. In the group of young with uncontrolled asthma, gingivitis was detected in 53.8% and alcohol consumption in 84.6%. Logistic regression analysis showed a significant association between allergic rhinitis, gingivitis, carbohydrate intake, alcohol consumption, overweight, and obesity with uncontrolled asthma. Parents and members of the health team need to identify on time the risk factors associated with uncontrolled asthma in young people with asthma to limit its development and the negative effects it generates. The results of this study should be used to strengthen programs that promote the comprehensive health of adolescents.
PubMed: 38957941
DOI: 10.1080/02770903.2024.2375270 -
Journal of Materials Chemistry. B Jul 2024Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity...
Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity separation. This study reports a novel hydrogel-coupled, paper-based analytical device (PAD) for separation-free HO colorimetric detection in both aqueous solution and cell lysis with sample-to-answer analysis by directly loading into the sample test zone. By encapsulating an inorganic mimic enzyme and chromogenic substrate into the sodium alginate (SA) hydrogel, amplification of the color signal after catalyzing the substrate could be achieved. Taking advantage of the nanoscale porous structure of the hydrogel and the lateral flow channel of the PAD, large interference fragments or bio-macromolecules are prevented from diffusing into the chromogenic reaction, whereas the small target molecules enter the sensing region to trigger the catalytic reaction. This method demonstrated a rapid and accurate analysis with a limit of detection as low as 0.06 mM and detection selectivity. Our proposed device requires no enzyme and is separation-free, portable, easy-to-fabricate, and low-cost, and may offer a platform for quantitative or qualitative analysis of other analytes in body fluids for POC applications.
PubMed: 38957936
DOI: 10.1039/d4tb00715h