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1.
Environ Sci Technol ; 58(18): 8065-8075, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38597221

RESUMEN

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.


Asunto(s)
Suelo , Suelo/química , Radicales Libres/química , Contaminantes del Suelo/química , Oxidación-Reducción , Halogenación
2.
Explore (NY) ; 20(2): 261-263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37673761

RESUMEN

BACKGROUND: Warts result from an infection with the human papilloma virus (HPV). Plantar warts, also known as Verruca plantaris, can be notably painful for the patient and possess contagious qualities, thus necessitating assertive treatment. Despite several available approaches for addressing plantar warts, efficacy remains elusive. CASE PRESENTATION: One 22-year-old firefighter suffered from numerous plantar warts. After 26 days of traditional Chinese medicine soaking, the rashes completely disappeared. The treatment was without complications or discomfort, and a three-month follow-up showed no recurrence. CONCLUSION: Our case investigation highlighted the efficacy of herbal soaking as a safe, painless, and non-invasive therapeutic option, positioning it as a potential avenue for managing multiple plantar warts.


Asunto(s)
Enfermedades del Pie , Verrugas , Humanos , Anciano de 80 o más Años , Medicina Tradicional China , Verrugas/tratamiento farmacológico , Enfermedades del Pie/terapia , Papillomaviridae , Resultado del Tratamiento
3.
Int Dent J ; 74(1): 88-94, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37758581

RESUMEN

INTRODUCTION: The Chinese traditional herbs Cortex Moutan, Poria cocos, and Alisma orientale are considered to have potential to ameliorate periodontitis, although the possible underlying mechanisms remain mostly unknown. Due to the complex formulation of Chinese herbs, it is important to understand the mechanisms of pharmacologic effects of traditional herbs for better application in modern medical treatment. METHODS: Network pharmacology was applied to explore the mechanism of Cortex Moutan, Poria cocos, and Alisma orientale. First we analysed their chemical ingredients using the Traditional Chinese Medicine Systems Pharmacology database and identified 20 active ingredients. Then we analysed the target genes of these 20 active ingredients as well as genes associated with periodontitis and found 74 co-target genes. We further analysed the protein-protein interaction network of these 74 co-target genes using the STRING database and enriched the pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: The top 10 core targets elicited were vascular endothelial growth factor A (VEGFA), interlukin-6 (IL-6), tumour necrosis factor (TNF), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), and serpin family E member 1 (SERPINE1). Using these a network of "herbs-ingredients-targetgenes-KEGG pathways." was constructed. CONCLUSIONS: The target and bioprocess network suggested that the pharmacologic effects of Cortex Moutan, Poria cocos, and Alisma orientale may be mainly dependent on their anti-inflammatory potential. Further work is required to eucidate their detailed mechanisms of activity.


Asunto(s)
Alisma , Periodontitis , Wolfiporia , Humanos , Metaloproteinasa 2 de la Matriz , Alisma/química , Factor A de Crecimiento Endotelial Vascular
4.
Biochim Biophys Acta Gen Subj ; 1868(1): 130518, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37951369

RESUMEN

BACKGROUND: Zinc deficiency can lead to multiple organ damage. In this study, we investigated the effects of zinc deficiency on obesity-related lung damage. METHODS: C57BL/6 J mice were fed a diet with differing amounts of zinc and fat over a 6-month period. Palmitic acid was used to stimulate A549 cells to construct a high-fat alveolar epithelial cell model. Western blotting and histopathological staining were performed on animal tissues. Nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was detected in cultured cells. A reactive oxygen species (ROS) assay kit was used to detect intracellular ROS. Furthermore, Nrf2 siRNA was used to examine zinc deficiency effects on A549 cells. RESULTS: Pathological results showed significant damage to the lung structure of mice in the high-fat and low-zinc diet group, with a significant increase in the expression of inflammatory (IL-6, TNF-α) and fibrosis (TGFß1, PAI-1) factors, combined with a decrease in the expression of Nrf2, HO-1 and NQO1 in the antioxidant pathway. In A549 cells, high fat and low zinc levels aggravated ROS production. Western blot and immunofluorescence results showed that high fat and zinc deficiency inhibited Nrf2 expression. After Nrf2-specific knockout in A549 cells, the protective effect of zinc on oxidant conditions induced by high fat was reduced. Phosphorylated Akt and PI3K levels were downregulated on the high-fat and low-zinc group compared with the high-fat group. CONCLUSIONS: Zinc attenuated lung oxidative damage in obesity-related lung injury and Nrf2 activation is one of the important mechanisms of this effect. GENERAL SIGNIFICANCE: Regulating zinc homeostasis through dietary modifications or supplemental nutritional therapy can contribute to the prevention and treatment of obesity-related lung injury.


Asunto(s)
Lesión Pulmonar , Neumonía , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones Obesos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Ratones Endogámicos C57BL , Estrés Oxidativo , Fibrosis , Zinc , Obesidad/complicaciones
5.
Medicine (Baltimore) ; 102(40): e34943, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37800756

RESUMEN

BACKGROUND: Although increasing evidence has revealed the efficacy of acupuncture in obesity/overweight, actual improvement in metabolism in children and adolescents is unclear. Therefore, we conducted a meta-analysis to evaluate this correlation. METHODS: A comprehensive search was conducted using multiple databases, including Medline, Cochrane, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Data, to identify relevant randomized controlled trials published before February 1, 2023. General information and data for the descriptive and quantitative analyses were extracted. RESULTS: Fifteen randomized controlled trials of 1288 obese/overweight children and teenagers were included. All the trials were conducted in China and South Korea. Regarding quality assessment, no other significant risk of bias was found. The acupuncture groups were more likely to have improved metabolic indicators of obesity/overweight than the control groups, in terms of body mass index (standardized mean difference [SMD] = -0.45, 95% confidence interval [CI]: -0.69 to -0.21, I2 = 71.4%), body weight (SMD = -0.48, 95% CI: -0.92 to -0.05, I2 = 84.9%), and serum leptin (SMD = -0.34, 95% CI: -0.58 to -0.10, I2 = 91.8%). The subgroup analysis showed that for body mass index, the results were consistent regardless of the intervention duration, body acupuncture or auricular acupuncture combined with other interventions. CONCLUSION: Our results suggest that acupuncture is effective in improving metabolic outcomes of obese/overweight children and adolescents. Owing to the limited number of trials included in this study, the results should be interpreted with caution.


Asunto(s)
Terapia por Acupuntura , Sobrepeso , Adolescente , Humanos , Niño , Sobrepeso/terapia , Obesidad/terapia , Terapia por Acupuntura/métodos , Índice de Masa Corporal , China
6.
Front Cardiovasc Med ; 10: 1147740, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37564906

RESUMEN

Introduction: Preventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further. Methods: We conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022. Results: Seventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: -3.60,95% CI: -4.45 to -2.74, P < 0.01, I2: 84.7%, P < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, P < 0.01, I2: 82.9%, P < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, P < 0.001, I2: 81.3%, P < 0.001). Discussion: The results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.

7.
CNS Neurosci Ther ; 29(12): 3829-3841, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37309308

RESUMEN

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.


Asunto(s)
Corteza Motora , Humanos , Corteza Motora/fisiología , Inhibición Neural/fisiología , Ácido Glutámico/metabolismo , Estimulación Magnética Transcraneal , Potenciales Evocados Motores/fisiología , Ácido gamma-Aminobutírico/metabolismo , Neurotransmisores/metabolismo
8.
Biomed Pharmacother ; 163: 114598, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37150034

RESUMEN

Diabetic kidney disease (DKD) has become the major cause of chronic kidney disease or end-stage renal disease. There is still a need for innovative treatment strategies for preventing, arresting, treating, and reversing DKD, and a plethora of scientific evidence has revealed that Chinese herbal monomers can attenuate DKD in multiple ways. Astragaloside IV (AS-IV) is one of the active ingredients of Astragalus membranaceus and was selected as a chemical marker in the Chinese Pharmacopeia for quality control purposes. An increasing amount of studies indicate that AS-IV is a promising novel drug for the treatment of DKD. AS-IV has been shown to improve DKD by combating oxidative stress, attenuating endoplasmic reticulum stress, regulating calcium homeostasis, alleviating inflammation, improving vascular function, improving epithelial to mesenchymal transition and so on. This review briefly summarizes the pathogenesis of DKD, systematically reviews the mechanisms by which AS-IV improves DKD, and aims to facilitate related pharmacological research and development to promote the utilization of Chinese herbal monomers in DKD.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Saponinas , Triterpenos , Humanos , Nefropatías Diabéticas/patología , Transición Epitelial-Mesenquimal , Saponinas/farmacología , Saponinas/uso terapéutico , Triterpenos/farmacología , Triterpenos/uso terapéutico , Riñón , Diabetes Mellitus/tratamiento farmacológico
9.
Neuron ; 111(15): 2414-2431.e7, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37224813

RESUMEN

Pain and itch are two closely related but essentially distinct sensations that elicit different behavioral responses. However, it remains mysterious how pain and itch information is encoded in the brain to produce differential perceptions. Here, we report that nociceptive and pruriceptive signals are separately represented and processed by distinct neural ensembles in the prelimbic (PL) subdivision of the medial prefrontal cortex (mPFC) in mice. Pain- and itch-responsive cortical neural ensembles were found to significantly differ in electrophysiological properties, input-output connectivity profiles, and activity patterns to nociceptive or pruriceptive stimuli. Moreover, these two groups of cortical neural ensembles oppositely modulate pain- or itch-related sensory and emotional behaviors through their preferential projections to specific downstream regions such as the mediodorsal thalamus (MD) and basolateral amygdala (BLA). These findings uncover separate representations of pain and itch by distinct prefrontal neural ensembles and provide a new framework for understanding somatosensory information processing in the brain.


Asunto(s)
Complejo Nuclear Basolateral , Corteza Prefrontal , Ratones , Animales , Corteza Prefrontal/fisiología , Vías Nerviosas/fisiología , Tálamo/fisiología , Dolor
10.
Anal Bioanal Chem ; 415(4): 639-648, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36434171

RESUMEN

Electrocatalytic reactions based on electron transfer mediators provide a simple and effective route for the development of convenient and sensitive electrochemical assays. Here, we report a novel electrocatalytic assay for detection of EDTA-Fe(III), which is widely used as a supplement in iron-fortified foods to reduce prevalence of iron deficiency. Unlike conventional electrochemical methods to detect Fe(III) ion, signaling mechanism of our electrocatalytic assay relies on the previously unexplored thionine-mediated electrochemical reduction of EDTA-Fe(III). This electrocatalytic detection method is sensitive for EDTA-Fe(III) detection in the linear concentration range from 10 to 750 µM with a detection limit of 2.5 µM. It is also specific enough and applicable to detection of EDTA-Fe(III) in real soy sauce samples with satisfactory recovery. The one-step electrocatalytic reduction for signal generation enables the direct and sensitive electrochemical detection of EDTA-Fe(III). We believe that this electrocatalytic assay can serve as a general platform for quantification of EDTA-Fe(III) in many EDTA-Fe(III)-fortified foods. And because thionine is increasingly used as a signal reporter in electrochemical DNA/aptamer sensors, the engineered electrocatalytic reaction of thionine-mediated electrochemical reduction of EDTA-Fe(III) will also provide a simple signal amplification means for the development of highly sensitive electrochemical biosensors.


Asunto(s)
Compuestos Férricos , Alimentos de Soja , Ácido Edético , Fenotiazinas
11.
Zhongguo Zhong Yao Za Zhi ; 47(21): 5700-5707, 2022 Nov.
Artículo en Chino | MEDLINE | ID: mdl-36471988

RESUMEN

Under the background of the "14th Five-Year Plan" industry development, the pharmaceutical industry has ushered in a critical period of strategic transformation. Pharmaceutical excipients are a major categoryin drugs in addition tomedicinal substances, and the research and development of industrial technologies and innovative products play a decisive role in the development of high-quality drugs. The special drug for children is the focus ofthe pharmaceutical industry in the new era, and the application of standar-dized excipients is a key step indistinguishingbetween adult drugs and special drugs for children. In the context of the policy background in China, this paper reviewed the status quo of excipient industry, technical bottlenecks, application problems of pediatric excipients, and their development hotspots, interpreted the strategic layout of excipient innovation research and development suitable for pediatric preparations, and put forward prospects for their future development technicalroutes to lay a solid foundation for the industry transformation.


Asunto(s)
Industria Farmacéutica , Excipientes , Humanos , Niño , China , Preparaciones Farmacéuticas
12.
Front Neurol ; 13: 1030747, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388196

RESUMEN

Ischemic stroke is the predominant cause of long-term disability and death worldwide. It is attributable to the sudden interruption of regional cerebral blood flow, resulting in brain cell death and neurological impairment. Acupuncture is a widely used adjuvant treatment for ischemic stroke in China and shows promising efficacy in clinical practice. This review mainly focused on the evidence to illustrate several possible mechanisms of acupuncture therapy on cerebral perfusion in ischemic stroke. Studies have shown that acupuncture is probably effective in the enhancement of cerebral perfusion after ischemic stroke. It promotes the improvement of hemodynamics, the release of vasoactive substances, the formation of new blood vessels, as well as the restitution of microcirculation. Multiple factors may contribute to the variability in acupuncture's therapeutic effects, including the acupoint selection, stimulation frequency and intensity, and retaining needle time. Acupuncture has the potential to become a non-pharmacological adjuvant approach to enhance cerebral perfusion in ischemic stroke. Future studies are required to gain our insight into acupuncture as well as accelerate its clinical translation.

13.
Front Cardiovasc Med ; 9: 984251, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211564

RESUMEN

Background: Acute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure. Methods and results: We retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups. Conclusion: DAT could be a feasible and safe method to deal with APT during AF-CA procedure.

14.
Drugs ; 82(15): 1527-1538, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36287379

RESUMEN

BACKGROUND: Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection. METHODS: A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment. RESULTS: Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events. CONCLUSIONS: RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months. CLINICAL TRIAL REGISTRATION: NCT03244644; 9 August, 2017.


Clostridioides difficile is a diarrhea-causing bacterium that is associated with potentially serious and fatal consequences. Antibiotics used to treat or prevent infections have a side effect of damaging the healthy protective gut bacteria (microbiota). Damage to the gut microbiota can allow C. difficile to over-grow and produce toxins that injure the colon. Paradoxically, the standard of care treatment of C. difficile infection (CDI) is antibiotics. Although initially effective for the control of diarrhea, antibiotics can leave a patient at risk for CDI recurrence after antibiotic treatment is stopped. Live biotherapeutic products are microbiota-based treatments used to repair the gut microbiota. These products have been shown to reduce the recurrence of CDI. RBX2660 is an investigational microbiota-based live biotherapeutic. RBX2660 contains a diverse set of microorganisms. RBX2660 has been developed to reduce CDI recurrence in adults following antibiotic treatment for recurrent CDI. This study was conducted to demonstrate that RBX2660 is effective and safe in treating patients with recurrent CDI. Treatment was considered successful in participants who did not experience CDI recurrence within 8 weeks after administration. Overall, statistical modeling demonstrated that 70.6% of participants treated with RBX2660 and 57.5% of participants treated with placebo remained free of CDI recurrence through 8 weeks. A 13.1 percentage point increase in treatment success was observed with RBX2660 treatment compared with placebo. In participants who achieved treatment success at 8 weeks, more than 90% remained free of CDI recurrence through 6 months. The most common side effects with RBX2660 treatment were abdominal pain and diarrhea. No serious treatment-related side effects were reported. The current data from the comprehensive clinical development program support a positive benefit-risk profile for RBX2660 in the reduction of CDI recurrence in adults following antibiotic therapy for recurrent CDI.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Adulto , Humanos , Teorema de Bayes , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/prevención & control , Antibacterianos/efectos adversos , Resultado del Tratamiento , Recurrencia , Trasplante de Microbiota Fecal/efectos adversos
15.
Eur J Med Chem ; 243: 114707, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36057236

RESUMEN

Herein, we report the design, synthesis and evaluation of a novel series of diselenide and selenide derivatives as potent antifungal agents by exploiting the hydrophobic cleft of CYP51. Among all synthesized compounds, the most potent compound B01 with low cytotoxic and hemolysis effect exhibited excellent activity against C.alb., C.gla., C.par. and C.kru., as well as selected fluconazole-resistant strains. Moreover, compound B01 could reduce the biofilm formation of the FCZ-resistant C.alb. Subsequently, metabolic stability assays using liver microsomes demonstrated that compound B01 showed good profiles of metabolic stability. With superior pharmacological profile, compound B01 was advanced into in vivo bioactivity evaluation. In a murine model of systemic C.alb. infection, compound B01 significantly reduced fungal load of kidneys. Furthermore, compound B01 revealed relatively low acute toxicity and subacute toxicity in mice. In addition, docking study performed into C.alb. CYP51, showed the binding mode between C.alb. CYP51 and compound B01. Collectively, diselenides compound B01 can be further developed for the potential treatment of invasive fungal infections.


Asunto(s)
Antifúngicos , Selenio , Ratones , Animales , Antifúngicos/química , Azoles/química , Selenio/farmacología , Selenio/metabolismo , Candida albicans , Relación Estructura-Actividad , Pruebas de Sensibilidad Microbiana , Fluconazol/farmacología
16.
Adv Nutr ; 13(6): 2217-2236, 2022 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-36041185

RESUMEN

Unsaturated fatty acids might be involved in the prevention of and improvement in mental disorders, but the evidence on these associations has not been comprehensively assessed. This umbrella review aimed to appraise the credibility of published evidence evaluating the associations between unsaturated fatty acids and mental disorders. In this umbrella review, systematic reviews and meta-analyses of studies comparing unsaturated fatty acids (including supplementation, dietary intake, and blood concentrations) in participants with mental disorders with healthy individuals were included. We reanalyzed summary estimates, between-study heterogeneity, predictive intervals, publication bias, small-study effects, and excess significance bias for each meta-analysis. Ninety-five meta-analyses from 29 systematic reviews were included, encompassing 43 studies on supplementation interventions, 32 studies on dietary factors, and 20 studies on blood biomarkers. Suggestive evidence was only observed for dietary intake, in which higher intake of fish was associated with reduced risk of depression (RR: 0.78; 95% CI: 0.69, 0.89) and Alzheimer disease (RR: 0.74; 95% CI: 0.63, 0.87), and higher intake of total PUFAs might be associated with a lower risk of mild cognitive impairment (RR: 0.71; 95% CI: 0.61, 0.84). Evidence showed that PUFA supplementation was favorable but had weak credibility in anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), dementia, mild cognitive impairment, Huntington's disease, and schizophrenia (P-random effects <0.001-0.040). There was also weak evidence on the effect of decreased circulating n-3 (É·-3) PUFAs among patients on risk of ADHD, ASD, bipolar disorder, and schizophrenia (P-random effects <10-6-0.037). Our results suggest that higher levels of unsaturated fatty acids may relieve symptoms or reduce the risk of various mental disorders; however, the strength of the associations and credibility of the evidence were generally weak. Future high-quality research is needed to identify whether PUFA interventions should be prioritized to alleviate mental disorders.


Asunto(s)
Enfermedad de Alzheimer , Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Ácidos Grasos Omega-3 , Animales , Humanos , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Insaturados , Metaanálisis como Asunto
17.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3208-3214, 2022 Jun.
Artículo en Chino | MEDLINE | ID: mdl-35851113

RESUMEN

Uridine diphosphate rhamnose(UDP-Rha), a glycoside donor synthesized with the catalysis of rhamnose synthase(RHM), is one of the important elements in the synthesis of rhamnosides. In this study, we cloned a RHM gene from Citrus sinensis(CsRHM) and analyzed its bioinformatic information and functions in vitro. The results showed the gene consisted of an open reading frame of 2 007 bp encoding 668 amino acid residues. The deduced protein had a presumed molecular weight of 75.27 kDa, a theoretical isoelectric point of 6.97, and the characteristic signal sequences(GxxxGxxG/A and YxxxK) of the RHM family. Multiple sequence alignments and the phylogenetic tree demonstrated that CsRHM shared homology with other RHMs. The results of enzymatic reactions in vitro showed that the recombinant protein CsRHM catalyzed the conversion of UDP-Glu to UDP-Rha, with the kinetic parameters V_(max), K_m, K_(cat), and K_(cat)/K_m of 0.373 7 µmol·L~(-1)·min~(-1), 21.29 µmol·L~(-1), 0.24 s~(-1), and 1.13×10~4 s~(-1)·L·mol~(-1), respectively. This study is the first report about CsRHM with validated catalytic function in vitro, which provides a foundation for further research on the biosynthesis of UDP-Rha.


Asunto(s)
Citrus sinensis , Citrus sinensis/genética , Citrus sinensis/metabolismo , Clonación Molecular , Filogenia , Ramnosa/química , Ramnosa/metabolismo , Azúcares de Uridina Difosfato
18.
BMJ Open ; 12(7): e058172, 2022 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-35902195

RESUMEN

INTRODUCTION: Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension. METHODS AND ANALYSIS: This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure <140/90 mm Hg), proportion of patients taking antihypertensive drugs, change in number of antihypertensive drugs and changes in 12-item Short-Form. Tertiary outcomes will include change in body mass index, change in waist circumference, physical activity and medication adherence. Safety outcomes will be any serious adverse events and clinical events. ETHICS AND DISSEMINATION: This study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2000039400.


Asunto(s)
Antihipertensivos , Hipertensión , Puntos de Acupuntura , Antihipertensivos/uso terapéutico , Presión Sanguínea , Humanos , Hipertensión/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Teléfono Inteligente , Resultado del Tratamiento
19.
Oxid Med Cell Longev ; 2022: 3959390, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656019

RESUMEN

Diabetic cardiomyopathy (DCM) is the main factor responsible for poor prognosis and survival in patients with diabetes. The highly complex pathogenesis of DCM involves multiple signaling pathways, including nuclear factor-κB (NF-κB) signaling pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B (Akt) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and transforming growth factor-ß (TGF-ß) signaling pathway. Nuclear factor erythroid-2-related factor 2 (Nrf2) seems essential to the amelioration of the progression of DCM, not only through counterbalancing oxidative stress, but also through interacting with other signaling pathways to combat inflammation, the disorder in energy homeostasis and insulin signaling, and fibrosis. It has been evidenced that Chinese herbal monomers could attenuate DCM through the crosstalk of Nrf2 with other signaling pathways. This article has summarized the pathogenesis of DCM (especially in oxidative stress), the beneficial effects of ameliorating DCM via the Nrf2 signaling pathway and its crosstalk, and examples of Chinese herbal monomers. It will facilitate pharmacological research and development to promote the utilization of traditional Chinese medicine in DCM.


Asunto(s)
Diabetes Mellitus , Cardiomiopatías Diabéticas , Medicamentos Herbarios Chinos , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal
20.
Molecules ; 27(9)2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35566095

RESUMEN

As compared to China's overall oil reserves, the reserve share of offshore oilfields is rather significant. However, offshore oilfield circumstances for enhanced oil recovery (EOR) include not just severe temperatures and salinity, but also restricted space on offshore platforms. This harsh oil production environment requires polymers with relatively strong salt resistance, solubility, thickening ability, rapid, superior injection capabilities, and anti-shearing ability. As a result, research into polymers with high viscosity and quick solubility is recognized as critical to meeting the criteria of polymer flooding in offshore oil reservoirs. For the above purposes, a novel hydrophobically associating polymer (HAP) was prepared to be used for polymer flooding of Bohai offshore oilfields. The synthetic procedure was free radical polymerization in aqueous solutions starting at 0 °C, using acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and poly(ethylene glycol) octadecyl methacrylate (POM) as comonomers. It was discovered that under ideal conditions, the molecular weight of HAP exceeds 2.1 × 107 g⋅mol-1. In a simulated reservoir environment, HAP has substantially greater solubility, thickening property, and salt resistance than conventional polyacrylamide (HPAM), with equivalent molecular weight. Finally, the injectivity and propagation of the two polymers in porous media were investigated. Compared with HPAM, which has a similar molecular weight, HAP solution with the concentration of 0.175% had a much better oil displacement effect in the porous medium, which can enhance oil recovery by 8.8%. These discoveries have the potential to pave the way for chemical EOR in offshore oilfields.


Asunto(s)
Petróleo , Polímeros , Yacimiento de Petróleo y Gas , Polimerizacion , Polímeros/química , Agua de Mar
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