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1.
Bioelectrochemistry ; 161: 108796, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39244917

RESUMEN

Targeting oxidative phosphorylation of bacteria is a novel antibiotic strategy leading to rapid cell death as a result of respiration suppress. Herein, a conductive polymer termed polypyrrole (PPy) is used to short-circuit the electron transfer chain (ETC) of bacteria cells owing to its higher electron affinity to electrons than all of the electron carriers on ETC. A hydrogel is fabricated using PPy which is anticipated to seize electrons from ETC and inhibit respiration of bacteria cells. The results show that the prepared PPy hydrogel can mediate an effective direct current (DC) antibacterial therapy which greatly enhances intracellular reactive oxygen species (ROS) level of Escherichia coli (E. coli), suppresses respiration, induces apoptosis-like cell death of E. coli accompanied by chromosomal condensation and loss of structural integrity, and rapidly cleared E. coli infection in vivo. Taken into the photothermal property of PPy, a combined direct current-photothermal therapy is developed which can enhance bacteria-killing effects with the assistance of an 808 nm laser. Our findings provide a new antibiotic strategy with metabolic pathway as a target.

2.
Phytomedicine ; 134: 155993, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39244943

RESUMEN

BACKGROUND: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress. AIM OF THE STUDY: To explore the cardioprotective mechanism of LTC against MIRI. MATERIALS AND METHODS: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca2+and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress. RESULTS: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67phox), and reduced ROS production. CONCLUSION: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI.

3.
Heliyon ; 10(17): e37249, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286188

RESUMEN

Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights. Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs' therapeutic mechanisms. Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1. Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.

4.
Gene ; : 148949, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278374

RESUMEN

C-terminal kinesin motor KIFC1 is increasingly concerned with an essential role in germ cell development. During the spermatogenesis of mice, rats, and crustaceans, KIFC1 functions in regulating meiotic chromosome separation, acrosome vesicle transportation, and nuclear morphology maintenance. The expression pattern of KIFC1 is conservatively concentrated at the acrosome and nucleus of haploid sperm cells. However, whether KIFC1 has similar functions in non-human primates remains unknown. In this study, we constructed the testis-specific cDNA library and cloned different transcripts of KIFC1 based on the genomic sequence. New variants of KIFC1 were identified, and showed different functional domains from the predicted isoforms. The spatio-temporal expression of KIFC1 proteins in seminiferous tubules of rhesus monkeys showed an obvious nuclear localization, specifically expressed in the spermatocytes and early haploid spermatids. The transcripts of KIFC1 also exhibited considerable expression in the nucleus of rhesus LLC-MK2 cells. Besides, we demonstrated that KIFC1 located at the acrosome and microtubule flagella of the mature sperm, and KIFC1 inhibition resulted in sperm tail deformation as well as increased the instability of head-to-tail connection. In summary, this study filled a gap in the reproductive research of the KIFC1 gene in non-human primates.

6.
Commun Biol ; 7(1): 1058, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191900

RESUMEN

Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.


Asunto(s)
Microscopía por Crioelectrón , Microscopía por Crioelectrón/métodos , SARS-CoV-2/química , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Glicoproteína de la Espiga del Coronavirus/metabolismo , Conformación Proteica , Procesamiento de Imagen Asistido por Computador/métodos , Humanos
8.
Microb Pathog ; 195: 106877, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173853

RESUMEN

BACKGROUND: Candida albicans is an opportunistic pathogen commonly found in human mucous membranes. In light of the escalating challenge posed by antibiotic resistance of C. albicans strains worldwide, it is an urgently necessary to explore alternative therapeutic options. OBJECTIVE: This study aims to assess the efficacy of two Cinnamaldehyde derivatives, 2-Cl Cinnamaldehyde (2-Cl CA) and 4-Cl Cinnamaldehyde (4-Cl CA), against C. albicans through both in vitro experiments and in vivo murine models and to evaluate their potential as new drug candidates for treating C. albicans. METHODS AND RESULTS: The minimum inhibitory concentrations (MICs) of Cinnamaldehyde 2-Cl and 4-Cl benzene ring derivatives against C. albicans were 25 µg/mL. Time-killing experiments revealed that both Cinnamaldehyde derivatives exhibited fungicidal activity against C. albicans at concentrations of 5 MIC and 10 MIC. In the checkerboard experiment, 4-Cl CA did not show any antagonistic effect when combined with first-line antifungal drugs. Instead, it exhibited additive effects in combination with nystatin. Both 2-Cl and 4-Cl CA demonstrated inhibitory activity against C. albicans biofilm formation, especially at 8 MIC and 16 MIC concentrations. In C. albicans biofilm eradication experiments, although high drug concentrations of 2-Cl and 4-Cl CA were unable to eradicate the biofilm completely, they were still effective in killing C. albicans cells within the biofilm. Moreover, sub-inhibitory concentrations of 4-Cl CA (ranging from 5 to 20 µg/mL) significantly inhibited cell aggregation and hyphal formation. Furthermore, 4-Cl CA effectively inhibited intracellular C. albicans infection in macrophages. Lastly, the effectiveness of 4-Cl CA was evaluated in a mouse model of hematogenous disseminated candidiasis caused by C. albicans, which revealed that 4-Cl CA significantly reduced fungal burden and improved mouse survival compared to the untreated controls. CONCLUSION: The 4-Cl CA exhibited inhibitory effects against C. albicans through both in vivo and in vitro models, demonstrating its therapeutic potential as a promising new drug candidate for treating drug-resistant candidiasis albicans.


Asunto(s)
Acroleína , Antifúngicos , Biopelículas , Candida albicans , Candidiasis , Modelos Animales de Enfermedad , Farmacorresistencia Fúngica , Fluconazol , Pruebas de Sensibilidad Microbiana , Acroleína/análogos & derivados , Acroleína/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Animales , Biopelículas/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Ratones , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Fluconazol/farmacología , Femenino , Ratones Endogámicos BALB C
9.
STAR Protoc ; 5(3): 103267, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154346

RESUMEN

Bacillus Calmette-Guérin (BCG), the only licensed tuberculosis vaccine, provides non-specific protection against non-tuberculosis diseases that is mediated by trained immunity, a functional reprogramming mediated by innate immune memory. Here, we present a protocol for analyzing BCG-induced trained immunity in murine bone marrow-derived macrophages (BMDMs). We describe steps for preparing BCG single bacterial suspensions, isolating BMDM cells, and the training process. This protocol can assist researchers to conveniently utilize BMDM cells to study trained immunity. For complete details on the use and execution of this protocol, please refer to Xu et al.1.

10.
Ultrasound Med Biol ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39097493

RESUMEN

OBJECTIVE: To explore the performance of ultrasound image-based radiomics in predicting World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading of clear-cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted via histopathological examination on participants with ccRCC from January 2021 to August 2023. Participants were randomly allocated to a training set and a validation set in a 3:1 ratio. The maximum cross-sectional image of the lesion on the preoperative ultrasound image was obtained, with the region of interest (ROI) delineated manually. Radiomic features were computed from the ROIs and subsequently normalized using Z-scores. Wilcoxon test and least absolute shrinkage and selection operator (LASSO) regression were applied for feature reduction and model development. The performance of the model was estimated by indicators including area under the curve (AUC), sensitivity and specificity. RESULTS: A total of 336 participants (median age, 57 y; 106 women) with ccRCC were finally included, of whom 243 had low-grade tumors (grade 1-2) and 93 had high-grade tumors (grade 3-4). A total of 1163 radiomic features were extracted from the ROIs for model construction and 117 informative radiomics features selected by Wilcoxon test were submitted to LASSO. Our ultrasound-based radiomics model included 51 features and achieved AUCs of 0.90 and 0.79 for the training and validation sets, respectively. Within the training set, the sensitivity and specificity measured 0.75 and 0.92, respectively, whereas in the validation set, the sensitivity and specificity measured 0.65 and 0.84, respectively. In the subgroup analysis, for the training and validation sets Philips AUCs were 0.91 and 0.75, Toshiba AUCs were 0.82 and 0.90, and General Electric AUCs were 0.95 and 0.82, respectively. CONCLUSION: Ultrasound-based radiomics can effectively predict the WHO/ISUP grading of ccRCC.

11.
World J Clin Cases ; 12(22): 5236-5244, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109039

RESUMEN

BACKGROUND: Macrodactyly is a rare congenital malformation characterized by an increase in the size of all structures of a digit, accounting for less than 1% of all congenital upper extremity conditions. CASE SUMMARY: We report a case involving a 49-year-old woman who presented for the first time with untreated, radial-sided hand macrodactyly. We performed soft tissue debulking, amputation, median nerve neurotomy and coaptation, and carpal tunnel release. At the 6-year follow-up, no significant growth was observed in the bone or soft tissue of the affected area. CONCLUSION: Tissue overgrowth in patients with progressive macrodactyly can continue and progress excessively with age. Median nerve neurotomy and coaptation play a crucial role in preventing recurrence of the deformity.

12.
BMC Cancer ; 24(1): 985, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123182

RESUMEN

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Microondas , Vena Porta , Ablación por Radiofrecuencia , Humanos , Hepatectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Quimioembolización Terapéutica/métodos , Ablación por Radiofrecuencia/métodos , Microondas/uso terapéutico , Estudios Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirugía , Anciano , Adulto , Hígado/cirugía , Hígado/irrigación sanguínea , Embolización Terapéutica/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Tasa de Supervivencia , China/epidemiología , Terapia Combinada
13.
Environ Res ; 259: 119563, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38971358

RESUMEN

This study aimed to elucidate the effects of coastal environmental stress on the composition of sediment bacterial communities and their cooccurrence patterns in fishing harbors around the Bohai Economic Circle, China. Compared with the natural sea area, fishing harbors contained higher levels of organic pollution (organic pollution index = 0.12 ± 0.026) and considerably reduced bacterial richness and evenness. The distributions of sediment microbial communities clustered along the pollutant concentration gradients across fishing harbors. Betaproteobacteria dominated (76%) organically polluted fishing harbors, which were mostly disturbed by anthropogenic activities. However, the harbors also revealed the absence of numerous pathogenic (Coxiella and Legionella) and photosynthetic (Synechococcus and Leptolyngbya) bacteria. Abundant genera, including Thiobacillus and Arenimonas, exhibited a positive correlation with total phosphorus and a negative correlation with total nitrogen in sediments. Meanwhile, Sulfurovum, Psychrobacter, and Woeseia showed the opposite trend. Pollutant accumulation and anthropogenic activities caused the decrease in the sediment microbial diversity and dispersal ability and promoted convergent evolution. Severely polluted harbors with simplified cooccurrence networks revealed the presence of destabilized microbial communities. In addition, the modularity of bacterial networks decreased with organic pollution. Our results provide important insights into the adjustment mechanism of microbial communities to community organization and functions under environmental pollution stress. Overall, this study enhanced our understanding of how microbial communities in coastal sediments adapted and survived amidst anthropogenic activities like oily effluent discharges from large ships, wash water, domestic sewage, garbage, and fisheries wastes. It also examined their resilience to future contamination.


Asunto(s)
Bacterias , Sedimentos Geológicos , Microbiota , China , Bacterias/clasificación , Sedimentos Geológicos/microbiología , Monitoreo del Ambiente , Explotaciones Pesqueras
14.
Int Immunopharmacol ; 139: 112811, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39068754

RESUMEN

The eradication of tuberculosis remains a global challenge. Despite being the only licensed vaccine, Bacillus Calmette-Guérin (BCG) confers limited protective efficacy in adults and individuals with latent tuberculosis infections (LTBI). There is an urgent need to develop novel vaccines that can enhance the protective effect of BCG. Protein subunit vaccines have garnered significant research interest due to their safety and plasticity. Based on previous studies, we selected three antigens associated with LTBI (Rv2028c, Rv2029c, Rv3126c) and fused them with an immunodominant antigen Ag85A, resulting in the construction of a multistage protein subunit vaccine named A986. We evaluated the protective effect of recombinant protein A986 adjuvanted with MPL/QS21 as a booster vaccine for BCG against Mycobacterium tuberculosis (Mtb) infection in mice. The A986 + MPL/QS21 induced the secretion of antigen-specific Th1 (IL-2+, IFN-γ+ and TNF-α+) and Th17 (IL-17A+) cytokines in CD4+ and CD8+ T cells within the lung and spleen of mice, while also increased the frequency of central memory and effector memory T cells. Additionally, it also induced the enhanced production of IgG antibodies. Compared to BCG alone, A986 + MPL/QS21 boosting significantly augmented the proliferation of antigen-specific multifunctional T cells and effectively reduced bacterial load in infected mice. Taken together, A986 + MPL/QS21 formulation induced robust antigen-specific immune responses and provided enhanced protection against Mtb infection as a booster of BCG vaccine.


Asunto(s)
Antígenos Bacterianos , Vacuna BCG , Citocinas , Mycobacterium tuberculosis , Tuberculosis , Vacunas de Subunidad , Animales , Vacunas de Subunidad/inmunología , Mycobacterium tuberculosis/inmunología , Vacuna BCG/inmunología , Antígenos Bacterianos/inmunología , Femenino , Tuberculosis/prevención & control , Tuberculosis/inmunología , Ratones , Citocinas/metabolismo , Inmunización Secundaria , Modelos Animales de Enfermedad , Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la Tuberculosis/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Ratones Endogámicos C57BL , Ratones Endogámicos BALB C , Aciltransferasas/inmunología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Proteínas Bacterianas/inmunología , Humanos
15.
Nat Med ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079993

RESUMEN

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

16.
Front Microbiol ; 15: 1415554, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952446

RESUMEN

Introduction: The unique dormancy of Mycobacterium tuberculosis plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate. Methods: To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites. Results and discussion: The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential in vivo and/or in vitro for M. tuberculosis provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for M. tuberculosis.

17.
Chin J Integr Med ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958885

RESUMEN

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.

19.
Knee Surg Sports Traumatol Arthrosc ; 32(9): 2440-2451, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39010713

RESUMEN

PURPOSE: The purpose of this study was to study the effects of the severity of preoperative bone marrow oedema (BME) on the postoperative short-term outcomes following bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) and to propose a new metric that combines volume and signal density to evaluate BME. METHODS: Sixty-five patients with symptomatic OLTs (<100 mm2) and preoperative BME, who received BMS in our institution from April 2017 to July 2021 with follow-ups of 3, 6 and 12 months, were analysed retrospectively. The area, volume and signal value of the BME were collected on preoperative magnetic resonance imaging. The enroled patients were divided into two groups according to the BME index (BMEI), which was defined as the product of oedema relative signal intensity and the relation of oedema volume to total talar volume. Visual analogue scale, American Orthopedic Foot and Ankle Society (AOFAS), Tegner, Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and Sports scores were assessed before surgery and at each follow-up. The relationship between the scores and the volume, relative signal intensity and BMEI was explored. RESULTS: Sixty-five patients with preoperative BME were divided into the mild (n = 33) and severe (n = 32) groups based on the BMEI. A significant difference was found for each score with the general linear model for repeated measures through all follow-up time points (p < 0.001). For the preoperative and 12-month postoperative changes of the enroled patients, 53 patients (81.5%) exceeded the minimal clinically important difference of AOFAS and 26 (40.0%) exceeded that of FAAM-sports in this study. The mild group showed significantly more improvement in AOFAS scores at 12 months (89.6 ± 7.0 vs. 86.2 ± 6.2) and FAAM-ADL scores at 6 months (83.6 ± 7.6 vs. 79.7 ± 7.7) and 12 months (88.5 ± 8.5 vs. 84.4 ± 7.7) than the severe group (p < 0.05). No significant difference of all the scores between the groups was found at 3 months. No significant correlation was found in each group between BMEI and clinical outcomes. CONCLUSION: The severity of the preoperative BME negatively affected short-term clinical outcomes following arthroscopic BMS for OLTs. Worse clinical outcomes were shown at postoperative 6 and 12 months in patients with a high preoperative BMEI, which could be a favourable parameter for assessing the severity of BME and assist in developing personalised rehabilitation plans and determining the approach and timing of surgery. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Artroscopía , Edema , Imagen por Resonancia Magnética , Índice de Severidad de la Enfermedad , Astrágalo , Humanos , Astrágalo/cirugía , Edema/etiología , Masculino , Femenino , Adulto , Estudios Retrospectivos , Enfermedades de la Médula Ósea/cirugía , Enfermedades de la Médula Ósea/etiología , Enfermedades de la Médula Ósea/diagnóstico por imagen , Persona de Mediana Edad , Resultado del Tratamiento , Médula Ósea , Adulto Joven , Periodo Preoperatorio , Cartílago Articular/cirugía
20.
Blood Press ; 33(1): 2380002, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39018205

RESUMEN

AIM: To explore the association between serum folate concentration and the prevalence of elderly diastolic hypertension. This study aims to identify potential relationships that could inform further research into the mechanisms underlying hypertension management. METHODS: Data from six NHANES cycles (2007-2008, 2009-2010, 2011-2012, 2013-2014, 2015-2016, and 2017-2018) were analysed for individuals aged over 60. Weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and restricted cubic spline (RCS) regression explored the serum folate concentration and elderly diastolic hypertension relationship. RESULTS: This study included 9,419 participants (4,734 females and 4,685 males) with a mean age of 70.0 ± 7.0 years. Among them, 360 were diagnosed with diastolic hypertension. In the fully adjusted model, there was a negative correlation between serum folate concentration and the prevalence of diastolic hypertension (OR 0.65; 95% CI: 0.52-0.82). When serum folate concentration levels were divided into quartiles (in µg/dL), the ORs for diastolic hypertension corresponding to Q2 (1.29-1.98), Q3 (1.99-3.08), and Q4 (3.09-5.56) levels compared to Q1 (0.18-1.28) were 1.41 (95% CI: 0.60-3.33), 0.48(95% CI: 0.20-1.16), and 0.35 (95% CI: 0.16-0.74), respectively, with a P for trend <.05. Restricted cubic spline plots showed a negative correlation between serum folate concentration and the prevalence of diastolic hypertension (non-linearity: p = .495). Subgroup analysis indicated that the negative correlation between serum folate concentration and the prevalence of diastolic hypertension was more significant in female participants (interaction p = .009). CONCLUSION: Higher serum folate concentration is associated with a lower prevalence of diastolic hypertension in the elderly.


What is the context?Diastolic hypertension, characterised by high blood pressure during the relaxation phase of the heartbeat.It significantly elevates the risk of cardiovascular diseases such as heart attacks and strokes.This study examines how serum folate levels relate to diastolic hypertension in the elderly, aiming to uncover correlations that inform future management strategies.What is new?This study investigated the relationship between serum folate concentration and the prevalence of diastolic hypertension in individuals aged over 60.Analysing data from multiple cycles of the National Health and Nutrition Examination Survey (NHANES), researchers found a noteworthy correlation between higher serum folate levels and a lower prevalence of diastolic hypertension.This association remained significant even after adjusting for various factors such as age, sex, and other health variables.What is the impact?The findings underscore the potential significance of folate intake in lowering the prevalence of diastolic hypertension among the elderly.It suggests avenues for further research into nutritional interventions targeting hypertension in this vulnerable population, potentially leading to more effective preventive measures and improved health outcomes.


Asunto(s)
Ácido Fólico , Hipertensión , Encuestas Nutricionales , Humanos , Ácido Fólico/sangre , Femenino , Hipertensión/sangre , Hipertensión/epidemiología , Masculino , Anciano , Persona de Mediana Edad , Prevalencia
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