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1.
Chemosphere ; 364: 143243, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233295

RESUMEN

Phthalic acid esters (PAE) are widely used as plasticizers and have been classified as ubiquitous environmental contaminants of primary concern. PAE have accumulated intensively in surface water, groundwater, and wastewaters; thus, PAE degradation is essential. In the present study, the ability of a saline soil bacteria (SSB)-consortium to degrade synthetic wastewater-phthalates with alkyl chains of different lengths, such as diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), and di (2-ethylhexyl) phthalate (DEHP) was characterized. A central composite design-response surface methodology was applied to optimize the degradation of each phthalate, where the independent variables were temperature (21-41 °C), pH (5.3-8.6) and PAE concentration (79.5-920.4 mg L-1), and Gas Chromatography-Mass Spectrometry was used to identify the metabolites generated during phthalate degradation. Optimal conditions were 31 °C, pH 7.0, and an initial PAE concentration of 500 mg L-1, where the SSB-consortium removed 84.9%, 98.47%, 99.09% and 98.25% of initial DEP, DBP, BBP, and DEHP, respectively, in 168h. A first-order kinetic model explained - the biodegradation progression, while the half-life of PAE degradation ranged from 12.8 to 29.8 h. Genera distribution of the SSB-consortium was determined by bacterial meta-taxonomic analysis. Serratia, Methylobacillus, Acrhomobacter, and Pseudomonas were the predominant genera; however, the type of phthalate directly affected their distribution. Scanning electron microscopy analysis showed that high concentrations (1000 mg L-1) of phthalates induced morphological alterations in the bacterial SSB-consortium. The metabolite profiling showed that DEP, DBP, BBP, and DEHP could be fully metabolized through the de-esterification and ß-oxidation pathways. Therefore, the SSB-consortium can be considered a potential candidate for bioremediation of complex phthalate-contaminated water resources.

2.
Curr Dev Nutr ; 8(9): 104436, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39279785

RESUMEN

Background: Milk provides essential crucial public health nutrients, including 3-4 nutrients of public health concern, yet dairy consumption has declined over time, leading most Americans to fall short of meeting Dietary Guidelines recommendations. Objectives: To investigate milk and beverage consumption trends in preschool-age children, along with nutrient intakes from beverages, and to analyze the potential impact of replacing nondairy beverages with milk through isocaloric substitution. Methods: Data from the National Health and Nutrition Examination Survey 2001-2018 for children aged 1-5 y (n = 4696) were used, and milk and other beverages intakes were estimated from the first 24-h in-person dietary recall. Nutrient intakes were determined using the United States Department of Agriculture's food and nutrient database for dietary studies. Changes in nutrient intakes of children aged 2-5 y were modeled assuming isocaloric substitution with milk of all nondairy beverages consumed during lunch and dinner combined. Sample-weighted analyses were performed using SAS 9.4, and significance was set at P < 0.01. Results: With the increasing age of children, the intake of milk decreased, whereas the intake of energy, caloric beverages excluding milk, and sugar-sweetened beverages increased. Daily intakes of energy, protein, fat, saturated fatty acids (SFA), calcium, magnesium, potassium, sodium, vitamin A, folate, vitamin B-12, and vitamin D from caloric beverages including milk decreased with age, whereas the daily intake of fiber and added sugar increased with age. With the isocaloric replacement of nondairy caloric beverages with milk at lunch and dinner among children aged 2-5 y, intake of protein, fat, SFAs, calcium, magnesium, potassium, sodium, vitamin A, folate, vitamin B-12, and vitamin D increased, whereas for intake of carbohydrate, fiber, total sugar, and added sugar decreased. Conclusions: The current findings indicate that increased efforts are needed to reverse the decrease in milk intake over time and as preschool children age and provide additional evidence to support specific dietary recommendations for milk.

3.
Sci Rep ; 14(1): 20476, 2024 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227621

RESUMEN

Single-strand DNA-binding proteins SSB/RPA are ubiquitous and essential proteins that bind ssDNA in bacteria/eukaryotes and coordinate DNA metabolic processes such as replication, repair, and recombination. SSB protects ssDNA from degradation by nucleases, while also facilitating/regulating the activity of multiple partner proteins involved in DNA processes. Using Spi- assay, which detects aberrantly excised λ prophage from the E. coli chromosome as a measure of illegitimate recombination (IR) occurrence, we have shown that SSB inhibits IR in several DSB resection pathways. The conditional ssb-1 mutation produced a higher IR increase at the nonpermissive temperature than the recQ inactivation. A double ssb-1 recQ mutant had an even higher level of IR, while showing reduced homologous recombination (HR). Remarkably, the ssb gene overexpression complemented recQ deficiency in suppressing IR, indicating that the SSB function is epistatic to RecQ. Overproduced truncated SSBΔC8 protein, which binds to ssDNA, but does not interact with partner proteins, only partially complemented recQ and ssb-1 mutations, while causing an IR increase in otherwise wild-type bacteria, suggesting that ssDNA binding of SSB is required but not sufficient for effective IR inhibition, which rather entails interaction with RecQ and likely some other protein(s). Our results depict SSB as the main genome caretaker in E. coli, which facilitates HR while inhibiting IR. In enabling high-fidelity DSB repair under physiological conditions SSB is assisted by RecQ helicase, whose activity it controls. Conversely, an excess of SSB renders RecQ redundant for IR suppression.


Asunto(s)
ADN de Cadena Simple , Proteínas de Unión al ADN , Proteínas de Escherichia coli , Escherichia coli , RecQ Helicasas , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , RecQ Helicasas/metabolismo , RecQ Helicasas/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/genética , Recombinación Genética , Mutación , Recombinación Homóloga
4.
J Oncol Pharm Pract ; : 10781552241271753, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39113536

RESUMEN

INTRODUCTION: Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. METHODS: We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). RESULTS: Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. CONCLUSIONS: The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39189116

RESUMEN

PURPOSE: The aim of the present study was to assess the effectiveness of balloon implantation in patients with irreparable supraspinatus tears alone or in combination with other rotator cuff (RC) tendon tears and the effect of several covariables, such as age, gender, status of the long head biceps, with or without tendon repair and regardless the number of tendon involved. METHODS: Patients enrolled from 'San Carlo' Hospital of Potenza (Italy, IT), from January 2012 to September 2014, underwent arthroscopic implantation of shoulder balloon by a single surgeon, and followed for 3 years. The American Shoulder and Elbow Surgeons (ASES) and Constant score (CS) were administered pre-, post-operatively at 12 months, and then annually. Patients were classified on the basis of the number of tendons involved in the tears and treatment performed, considering the reparability of the tendons themselves. Gleno-humeral joint osteoarthrosis (OA) was evaluated through shoulder radiographs and classified according to the Samilson-Prieto classification, at the first examination and at the final follow-up. Statistical improvements were evaluated using a variance model (least-squares means) and a T distribution test for the evaluation between different treatment groups. RESULTS: A total of 61 procedures were performed, and eight patients were lost during follow-up. The mean baseline CS was 30.2 ± 15.4 with statistically significant improvement, respectively, at 1-, 2- and 3-year follow-up to 69.3 ± 4.2, 74.6 ± 3.6 and 69.7 ± 5.1 respectively. ASES score at baseline was 22.5 ± 10.9, with a statistically significant improvement to 69.7 ± 9.2, 68 ± 17.8 and 71.2 ± 16.6 at 1-, 2- and 3-year follow-up, respectively. Tenotomy or absence of long head biceps at presentation did not influence results (n.s.), with no difference according to gender and age. At final follow-up, 24 patients (43.9%) showed progression of glenohumeral OA. One patient required secondary surgery for shoulder replacement after 18 months for persistent pain and one patient required implant removal following post-operative laser treatment. CONCLUSION: Arthroscopic rotator cuff tears repair with subacromial spacer balloon implantation showed statistically significant clinical and functional improvement at 3-year follow-up. Patients treated with combined partial repair and subacromial spacer balloon implantation experienced good results independent of gender, age, type of tear and long-head biceps tendon status. The risks related to this procedure appear to be minimal. LEVEL OF EVIDENCE: Level IV.

6.
Int J Biol Macromol ; 278(Pt 4): 135065, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39187111

RESUMEN

The application of CRISPR-Cas9 ribonucleoprotein (RNP) for gene editing is commonly used in plants and animals, but its application in bacteria has not been reported. In this study, we employed DNA single-strand binding protein (SSB) to construct an SSB/CRISPR-Cas9 RNP-editing system for non-homologous recombination and homologous recombination gene editing of the upp gene in bacteria. The RNP targeting the upp gene, along with SSB, was introduced into the protoplasts of Escherichia coli, Pseudomonas, and Bacillus subtilis. Transformants were obtained on plates containing 5-fluorouracil (5-FU) with gene editing efficiencies (percentage of transformants relative to the number of protoplasts) of 9.75 %, 5.02 %, and 8.37 %, respectively, and sequencing analysis confirmed 100 % non-homologous recombination. When RNP, SSB, and a 100-nucleotide single-stranded oligodeoxynucleotide (ssODN) donor were introduced into the protoplasts of these bacteria, transformants were obtained with editing efficiencies of 45.11 %, 30.13 %, and 27.18 %, respectively, and sequencing confirmed 100 % homologous recombination knockout of the upp gene. Additionally, introducing RNP, SSB, and a 100 base-pair double-stranded oligodeoxynucleotide (dsODN) donor containing a tetracycline resistance gene (tetR-dsODN) resulted in transformants on 5-FU plates with editing efficiencies of 35.94 %, 22.46 %, and 19.08 %, respectively, with sequencing confirming 100 % homologous recombination replacement of the upp gene with tetR. These results demonstrate that the SSB/CRISPR-Cas9 RNP system can efficiently, simply, and rapidly edit bacterial genomes without the need for plasmids. This study is the first to report the use of RNP-based gene editing in bacteria.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Ribonucleoproteínas , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Protoplastos/metabolismo , Bacterias/genética , Escherichia coli/genética , Recombinación Homóloga
8.
Cancers (Basel) ; 16(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39123453

RESUMEN

Osteosarcoma is an aggressive bone malignancy, molecularly characterized by acquired genome complexity and frequent loss of TP53 and RB1. Obtaining a molecular understanding of the initiating mutations of osteosarcomagenesis has been challenged by the difficulty of parsing between passenger and driver mutations in genes. Here, a forward genetic screen in a genetic mouse model of osteosarcomagenesis initiated by Trp53 and Rb1 conditional loss in pre-osteoblasts identified that Arid1a loss contributes to OS progression. Arid1a is a member of the canonical BAF (SWI/SNF) complex and a known tumor suppressor gene in other cancers. We hypothesized that the loss of Arid1a increases the rate of tumor progression and metastasis. Phenotypic evaluation upon in vitro and in vivo deletion of Arid1a validated this hypothesis. Gene expression and pathway analysis revealed a correlation between Arid1a loss and genomic instability, and the subsequent dysregulation of genes involved in DNA DSB or SSB repair pathways. The most significant of these transcriptional changes was a concomitant decrease in DCLRE1C. Our findings suggest that Arid1a plays a role in genomic instability in aggressive osteosarcoma and a better understanding of this correlation can help with clinical prognoses and personalized patient care.

9.
Plants (Basel) ; 13(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39204630

RESUMEN

The passion fruit, Passiflora edulis, recognized for its rich nutritional properties, has long been used for its varied ethnobotanical applications. This study investigates the therapeutic potential of P. edulis var. Tainung No. 1 rind extracts by examining their polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes such as elastase, tyrosinase, and hyaluronidase, and their ability to inhibit bacterial growth, single-stranded DNA-binding protein (SSB), and their cytotoxic effects on oral carcinoma cells. The acetone extract from the rind exhibited the highest levels of TPC, TFC, anti-SSB, and antibacterial activities. The antibacterial effectiveness of the acetone-extracted rind was ranked as follows: Escherichia coli > Pseudomonas aeruginosa > Staphylococcus aureus. A titration curve for SSB inhibition showed an IC50 value of 313.2 µg/mL, indicating the potency of the acetone extract in inhibiting SSB. It also significantly reduced the activity of enzymes associated with skin aging, particularly tyrosinase, with a 54.5% inhibition at a concentration of 100 µg/mL. Gas chromatography-mass spectrometry (GC-MS) analysis tentatively identified several major bioactive compounds in the acetone extract, including stigmast-5-en-3-ol, vitamin E, palmitic acid, stigmasterol, linoleic acid, campesterol, and octadecanoic acid. Molecular docking studies suggested some of these compounds as potential inhibitors of tyrosinase and SSB. Furthermore, the extract demonstrated anticancer potential against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation and inducing apoptosis. These results underscore the potential of P. edulis (Tainung No. 1) rind as a promising candidate for anti-skin aging, antibacterial, and anticancer applications, meriting further therapeutic investigation.

10.
Front Public Health ; 12: 1390253, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045163

RESUMEN

To show how sugar-sweetened beverage (SSB) taxes were framed in posts on Twitter (now known as X) through text and images, we conducted a content analysis on a sample of Tweets from California users posted between January 1, 2015 and December 31, 2018 about SSB taxes in Berkeley, San Francisco, Oakland, and/or Albany, California. We evaluated posts for information sources, arguments for or against SSB tax policies, and images used. We found that posts presented a mix of messages through text and images. The majority of posts (64%) included arguments supporting SSB taxes, 28% presented a neutral position (e.g., factual information) or a mix of both pro-and anti-tax arguments, and 8% opposed. One-third of posts included an image, almost half of which appeared to be stock photos from SSB advertisements: many of these were shared by medical and public health users. Some tax supporters also reposted messages and images from opposition campaigns and added their own criticisms. By reposting opponents' anti-tax messages and images of SSBs, tax supporters may have inadvertently promoted SSBs, reinforced opposition to SSB taxes, and normalized SSBs. While advocates effectively shared pro-tax arguments, they should also ensure that accompanying images reflect the solutions they seek, not just the problem they are trying to combat.


Asunto(s)
Salud Pública , Medios de Comunicación Sociales , Bebidas Azucaradas , Impuestos , Humanos , California , Bebidas Azucaradas/economía , Bebidas Gaseosas/economía
11.
bioRxiv ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38948847

RESUMEN

The Escherichia coli XPD/Rad3-like helicase, YoaA, and DNA polymerase III subunit, χ, are involved in E. coli DNA damage tolerance and repair. YoaA and χ promote tolerance to the DNA chain-terminator, 3 -azidothymidine (AZT), and together form the functional helicase complex, YoaA-χ. How YoaA-χ contributes to DNA damage tolerance is not well understood. E. coli single-stranded DNA binding protein (SSB) accumulates at stalled replication forks, and the SSB-χ interaction is required to promote AZT tolerance via an unknown mechanism. YoaA-χ and SSB interactions were investigated in vitro to better understand this DNA damage tolerance mechanism, and we discovered YoaA-χ and SSB have a functional interaction. SSB confers a substrate-specific effect on the helicase activity of YoaA-χ, barely affecting YoaA-χ on an overhang DNA substrate but inhibiting YoaA-χ on forked DNA. A paralog helicase, DinG, unwinds SSB-bound DNA in a similar manner to YoaA-χ on the substrates tested. Through use of ensemble experiments, we believe SSB binds behind YoaA-χ relative to the DNA ds/ss junction and show via single-molecule assays that SSB translocates along ssDNA with YoaA-χ. This is, to our knowledge, the first demonstration of a mechanoenzyme pulling SSB along ssDNA.

12.
Cureus ; 16(6): e62528, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39022488

RESUMEN

Sjogren's syndrome (SS) is an autoimmune disease characterized by inflammation of exocrine glands. The disorder predominantly affects middle-aged women. Autoantibodies, including anti-SS-A/Ro and anti-SS-B/La antibodies, are present in most cases of SS. These antibodies can cross the placenta and likely play a role in pregnancy complications as well as the development of neonatal lupus, resulting in congenital heart block (CHB). It is essential to monitor the fetus for CHB during pregnancy. In particular, screening with echocardiography and monitoring heart rate at home are recommended practices. Regarding medical management, hydroxychloroquine and glucocorticoids have shown promise in reducing cardiac manifestations, but further research is needed to elucidate their longer term efficacy and safety. This scoping review analyzes literature from 2001 to 2024, focusing on pregnancy outcomes among women with SS, clinical manifestations of neonatal lupus, the role of anti-SS-A/Ro and anti-SS-B/La antibodies in the development of neonatal lupus and CHB, and emphasizes the need for future research efforts to refine treatment protocols and enhance clinical care strategies for pregnant women with SS.

13.
Tissue Cell ; 89: 102464, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981186

RESUMEN

Women affected by different autoimmune diseases and displaying positivity for anti-Ro/SSA and anti-La/SSB autoantibodies are at high risk of adverse pregnancies in which placental dysfunction seems to play a determinant role. Sialylation is known to have important implications in the maintenance of the normal morpho-functional features of the placenta. Hence, the present study aimed to investigate possible changes in the distribution and content of sialic acids (Sias) with different glycosidic linkages (i.e., α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias, and polysialic acid) in placentas from anti-Ro/SSA- and anti-La/SSB-positive pregnant women with autoimmune diseases by using lectin histochemistry and polysialic acid immunohistochemistry. Our findings revealed lower levels of α2,3-linked Sias in the trophoblast and basement membrane and/or basal plasma membrane of the pathological cases respect to control placentas. Some vessels of the pathological cases displayed α2,3-linked Sias. α2,6-linked Sias positivity was detected in the trophoblast and in some vessels of the pathological cases, while in control samples it was present only in the vessels. Lower levels of polysialic acid were observed in the trophoblast of pathological cases compared to controls. Collectively, our findings suggest that multiple changes in the sialylation status of placenta might affect placental morpho-functional features in anti-Ro/SSA- and anti-La/SSB-positive pregnancies.


Asunto(s)
Placenta , Ácidos Siálicos , Humanos , Femenino , Embarazo , Placenta/metabolismo , Ácidos Siálicos/metabolismo , Adulto , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Anticuerpos Antinucleares/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patología
14.
Microorganisms ; 12(6)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38930484

RESUMEN

The precise editing of genes mediated by CRISPR-Cas9 necessitates the application of donor DNA with appropriate lengths of homologous arms and fragment sizes. Our previous development, SSB/CRISPR-Cas9, has demonstrated high efficiency in homologous recombination and non-homologous end joining gene editing within bacteria. In this study, we optimized the lengths and sizes of homologous arms of the donor DNA within this system. Two sets of donor DNA constructs were generated: one set comprised donors with only 10-100 bp homologous arms, while the other set included donors with homologous arms ranging from 10-100 bp, between which was a tetracycline resistance expression cassette (1439 bp). These donor constructs were transformed into Escherichia coli MG1655 cells alongside pCas-SSB/pTargetF-lacZ. Notably, when the homologous arms ranged from 10 to 70 bp, the transformation efficiency of non-selectable donors was significantly higher than that of selectable donors. However, within the range of 10-100 bp homologous arm lengths, the homologous recombination rate of selectable donors was significantly higher than that of non-selectable donors, with the gap narrowing as the homologous arm length increased. For selectable donor DNA with homologous arm lengths of 10-60 bp, the homologous recombination rate increased linearly, reaching a plateau when the homologous arm length was between 60-100 bp. Conversely, for non-selectable donor DNA, the homologous recombination rate increased linearly with homologous arm lengths of 10-90 bp, plateauing at 90-100 bp. Editing two loci simultaneously with 100 bp homologous arms, whether selectable or non-selectable, showed no difference in transformation or homologous recombination rates. Editing three loci simultaneously with 100 bp non-selectable homologous arms resulted in a 45% homologous recombination rate. These results suggest that efficient homologous recombination gene editing mediated by SSB/CRISPR-Cas9 can be achieved using donor DNA with 90-100 bp non-selectable homologous arms or 60-100 bp selectable homologous arms.

15.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38856168

RESUMEN

Nucleic acid-binding proteins (NABPs), including DNA-binding proteins (DBPs) and RNA-binding proteins (RBPs), play important roles in essential biological processes. To facilitate functional annotation and accurate prediction of different types of NABPs, many machine learning-based computational approaches have been developed. However, the datasets used for training and testing as well as the prediction scopes in these studies have limited their applications. In this paper, we developed new strategies to overcome these limitations by generating more accurate and robust datasets and developing deep learning-based methods including both hierarchical and multi-class approaches to predict the types of NABPs for any given protein. The deep learning models employ two layers of convolutional neural network and one layer of long short-term memory. Our approaches outperform existing DBP and RBP predictors with a balanced prediction between DBPs and RBPs, and are more practically useful in identifying novel NABPs. The multi-class approach greatly improves the prediction accuracy of DBPs and RBPs, especially for the DBPs with ~12% improvement. Moreover, we explored the prediction accuracy of single-stranded DNA binding proteins and their effect on the overall prediction accuracy of NABP predictions.


Asunto(s)
Biología Computacional , Proteínas de Unión al ADN , Aprendizaje Profundo , Proteínas de Unión al ARN , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ADN/metabolismo , Biología Computacional/métodos , Redes Neurales de la Computación , Humanos
16.
Biomed Phys Eng Express ; 10(4)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38870909

RESUMEN

Background. Radiation-induced DNA damages such as Single Strand Break (SSB), Double Strand Break (DSB) and Complex DSB (cDSB) are critical aspects of radiobiology with implications in radiotherapy and radiation protection applications.Materials and Methods. This study presents a thorough investigation into the effects of protons (0.1-100 MeV/u), helium ions (0.13-100 MeV/u) and carbon ions (0.5-480 MeV/u) on DNA of human fibroblast cells using Geant4-DNA track structure code coupled with DBSCAN algorithm and Monte Carlo Damage Simulations (MCDS) code. Geant4-DNA-based simulations consider 1µm × 1µm × 0.5µm water box as the target to calculate energy deposition on event-by-event basis and the three-dimensional coordinates of the interaction location, and then DBSCAN algorithm is used to calculate yields of SSB, DSB and cDSB in human fibroblast cell. The study investigated the influence of Linear Energy Transfer (LET) of protons, helium ions and carbon ions on the yields of DNA damages. Influence of cellular oxygenation on DNA damage patterns is investigated using MCDS code.Results. The study shows that DSB and SSB yields are influenced by the LET of the particles, with distinct trends observed for different particles. The cellular oxygenation is a key factor, with anoxic cells exhibiting reduced SSB and DSB yields, underscoring the intricate relationship between cellular oxygen levels and DNA damage. The study introduced DSB/SSB ratio as an informative metric for evaluating the severity of radiation-induced DNA damage, particularly in higher LET regions.Conclusions. The study highlights the importance of considering particle type, LET, and cellular oxygenation in assessing the biological effects of ionizing radiation.


Asunto(s)
Algoritmos , Carbono , Daño del ADN , ADN , Fibroblastos , Helio , Transferencia Lineal de Energía , Método de Montecarlo , Protones , Humanos , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Carbono/química , Iones , Roturas del ADN de Doble Cadena/efectos de la radiación , Simulación por Computador , Roturas del ADN de Cadena Simple/efectos de la radiación
17.
J Pharm Biomed Anal ; 246: 116239, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38777665

RESUMEN

The dried root of Bupleurum marginatum var. stenophyllum (H. Wolff) R.H. Shan & Y. Li (BM), which has been used as a Bupleuri radix in Guizhou Province and is listed in the 2003 edition of the Guizhou Quality Standard for Traditional Chinese Medicines and Ethnic Materia Medica, is effective at dispersing the liver and relieving depression and often used in the form of raw or vinegar-processed product (VBM). However, the potential depression-relieving components of BM are unclear. The aim of this study was to determine the potential antidepressant constituents of BM and investigate the effect of vinegar processing on these components. The antidepressant effect and mechanism of BM and VBM were investigated in depressed mice and BV2 cells, respectively. The pharmacodynamic constituents were screened through serum pharmacochemistry, which combined the results of metabolomics analysis of BM and VBM, high-performance liquid chromatography (HPLC) content determination, and verification of the antidepressant effect and mechanism of differential components of SSb2 to clarify the connotation of vinegar processing. Our results demonstrated that BM can exert a significant antidepressant effect by inhibiting microglia polarization and that this effect was enhanced after vinegar processing. Thirty-eight components were identified in the BM, 13 of which were blood-absorbable, mainly saponins, and defined as potential antidepressant components of the BM. The contents of 17 components-6 of which were absorbed into the blood-changed considerably after processing. It was finally determined that vinegar processing can enhance the antidepressant effect of BM by increasing the contents of SSb1 and SSb2. SSb2 exerts this effect via the samemechanism as BM. In conclusion, in this study we clarified the antidepressant effects and potential active components of BM and examined the mechanism of vinegar processing. These findings lay a foundation for the future research on the antidepressant effects of BM as well as for the complete development and application of BM's ethnomedicinal resources.


Asunto(s)
Ácido Acético , Antidepresivos , Bupleurum , Depresión , Medicamentos Herbarios Chinos , Metabolómica , Animales , Bupleurum/química , Antidepresivos/farmacología , Ratones , Metabolómica/métodos , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Depresión/tratamiento farmacológico , Depresión/metabolismo , Raíces de Plantas/química
18.
Crit Rev Biochem Mol Biol ; 59(1-2): 99-127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38770626

RESUMEN

The SSB protein of Escherichia coli functions to bind single-stranded DNA wherever it occurs during DNA metabolism. Depending upon conditions, SSB occurs in several different binding modes. In the course of its function, SSB diffuses on ssDNA and transfers rapidly between different segments of ssDNA. SSB interacts with many other proteins involved in DNA metabolism, with 22 such SSB-interacting proteins, or SIPs, defined to date. These interactions chiefly involve the disordered and conserved C-terminal residues of SSB. When not bound to ssDNA, SSB can aggregate to form a phase-separated biomolecular condensate. Current understanding of the properties of SSB and the functional significance of its many intermolecular interactions are summarized in this review.


Asunto(s)
ADN de Cadena Simple , Proteínas de Unión al ADN , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/química , ADN de Cadena Simple/genética , Unión Proteica , ADN Bacteriano/metabolismo , ADN Bacteriano/genética
19.
Clin Exp Med ; 24(1): 96, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717644

RESUMEN

Primary Sjögren's Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.


Asunto(s)
Anticuerpos Antinucleares , Síndrome de Sjögren , Humanos , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/patología , Síndrome de Sjögren/sangre , Femenino , Persona de Mediana Edad , Masculino , Adulto , Anciano , Inflamación/inmunología , Inflamación/patología , Inmunoglobulina G/sangre
20.
Mater Sociomed ; 36(1): 47-53, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590603

RESUMEN

Background: Autoimmune diseases encompass a diverse array of disorders that disturb the optimal functioning of the immune system, which is to eliminate the 'foreign or/and dangerous' to mistakenly target the body's own tissues. Objective: The aim of this research is to evaluate the most effective approach to managing autoimmune diseases within the framework of pregnancy. Methods: The exact causes and etiologies of these diseases are multifactorial and mostly still unclear. Ro/SSA autoantibodies and La/SSB, could be found in Sjögren's disease (SJ), systemic lupus (SLE) and other autoimmune disorders. Smoking, stress, UV exposure, vitamin D deficiency, and other genetic and environmental factors have been identified as risk factors for rheumatic diseases. Results: Over the years, an ever-increasing incidence of these diseases has been observed in the general population, with the female sex being at increased risk for their occurrence. This fact raises the question of what should be the management of these pathological entities during pregnancy. Taking into account the very significant impact on the quality of paitients'daily life and the seemingly augmented prevalence of autoimmune diseases, as well as their preference in the female population, the reasonable question arises as to what should be the optimal management of these diseases in the context of pregnancy. Conclusion: Given the limited data of the global medical community regarding the etiological factors and mechanisms that trigger the onset of rheumatic diseases, the management of pregnant women is a complex conundrum that health professionals are challenged to face and solve.

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