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1.
bioRxiv ; 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38014294

RESUMO

Increasing evidence shows that many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, much less is known about the mechanisms by which drugs target the microbiome and how drugs affect microbial function. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging to investigate the impact of two widely prescribed nervous system-targeted drugs on the gut microbiome. Ex vivo supplementation of physiologically relevant concentrations of entacapone or loxapine succinate to faecal samples significantly impacted the abundance of up to one third of the microbial species present. Importantly, we demonstrate that the impact of these drugs on microbial metabolism is much more pronounced than their impact on abundances, with low concentrations of drugs reducing the activity, but not the abundance of key microbiome members like Bacteroides, Ruminococcus or Clostridium species. We further demonstrate that entacapone impacts the microbiome due to its ability to complex and deplete available iron, and that microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Remarkably, entacapone-induced iron starvation selected for iron-scavenging organisms carrying antimicrobial resistance and virulence genes. Collectively, our study unveils the impact of two under-investigated drugs on whole microbiomes and identifies metal sequestration as a mechanism of drug-induced microbiome disturbance.

2.
Photobiomodul Photomed Laser Surg ; 41(2): 80-87, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36780574

RESUMO

Background: Blue light exhibits the ability to deactivate catalase present in pathogens, significantly improving the antimicrobial performance of compounds such as hydrogen peroxide (H2O2). However, H2O2 is not used within clinical settings due to its short half-life, limiting its potential applications. In this study, we explore the usage of Food and Drug Administration-approved and clinically used silver sulfadiazine (SSD) as a potential alternative to H2O2, acting as a reactive oxygen species (ROS)-producing agent capable of synergizing with blue light exposure. Materials and methods: For in vitro studies, bacterial strains were exposed to a continuous wave 405 nm light-emitting diode (LED) followed by treatment with SSD for varying incubation times. For in vivo studies, bacteria-infected murine abrasion wounds were treated with daily treatments of 405 nm LED light and 1% SSD cream for up to 4 days. The surviving bacterial population was quantified through agar plating and colony-forming unit quantification. Results: Through a checkerboard assay, blue light and SSD demonstrated synergistic interactions. Against both gram-negative and gram-positive pathogens, blue light significantly improved the antimicrobial response of SSD within both phosphate-buffered saline and nutrient-rich conditions. Examination into the mechanisms reveals that the neutralization of catalase significantly improves the ROS-producing capabilities of SSD at the exterior of the bacterial cell, producing greater amounts of toxic ROS capable of exerting antimicrobial activity against the pathogen. Additional experiments reveal that the incorporation of light improves the antimicrobial performance of SSD within methicillin-resistant Staphylococcus aureus (MRSA)- and Pseudomonas aeruginosa strain 1 (PAO-1)-infected murine abrasion wounds. Conclusions: As an established, clinically used antibiotic, SSD can act as a suitable alternative to H2O2 in synergizing with catalase-deactivating blue light, allowing for better translation of this technology to more clinical settings and further implementation of this treatment to more complex animal models.


Assuntos
Anti-Infecciosos , Luz , Sulfadiazina de Prata , Animais , Camundongos , Anti-Infecciosos/farmacologia , Catalase , Peróxido de Hidrogênio/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Espécies Reativas de Oxigênio , Sulfadiazina de Prata/farmacologia
3.
Proc Natl Acad Sci U S A ; 119(41): e2203480119, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36197994

RESUMO

Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated fatty acids (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme active in cancer. Here, we studied how the dynamics between SFAs and UFAs regulated by SCD impacts ovarian cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman scattering (SRS) microscopy. Further, increased levels of SFAs resulting from SCD knockdown triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Disorganized ER membrane was visualized by electron microscopy and SRS imaging in ovarian cancer cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of UFAs led to cell death. However, ER stress and apoptosis could be readily rescued by supplementation with UFAs and reequilibration of SFA/UFA levels. The effects of SCD knockdown or inhibition observed in vitro translated into suppression of intraperitoneal tumor growth in ovarian cancer xenograft models. Furthermore, a combined intervention using an SCD inhibitor and an SFA-enriched diet initiated ER stress in tumors growing in vivo and potently blocked their dissemination. In all, our data support SCD as a key regulator of the cancer cell fate under metabolic stress and point to treatment strategies targeting the lipid balance.


Assuntos
Sobrevivência Celular , Endorribonucleases , Ácidos Graxos Insaturados , Neoplasias Ovarianas , Progressão da Doença , Ácidos Graxos Dessaturases , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Feminino , Humanos , Fosfolipídeos , Proteínas Serina-Treonina Quinases , Estearoil-CoA Dessaturase/metabolismo
4.
Front Plant Sci ; 13: 878263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734262

RESUMO

Most plants of Ligusticum have an important medicinal and economic value with a long history, Ligusticum sinense and L. jeholense ("Gaoben") has long been used in traditional Chinese medicine for the treatment of carminative, dispelling cold, dehumidification, and analgesia. While in the market Conioselinum vaginatum (Xinjiang Gaoben) is substitution for Gaoben, and occupies a higher market share. These three Gaoben-related medicinal materials are similar in morphology, and are difficult to distinguish from each other by the commonly used DNA barcodes. The chloroplast genome has been widely used for molecular markers, evolutionary biology, and barcoding identification. In this study, the complete chloroplast genome sequences of C. vaginatum, L. sinense, and L. jeholense were reported. The results showed that the complete chloroplast genomes of these three species have typical quadripartite structures, which were comprised of 148,664, 148,539, and 148,497 bp. A total of 114 genes were identified, including 81 protein-coding genes (PCGs), 29 tRNA genes, and four rRNA genes. Our study indicated that highly variable region ycf2-trnL and accD-ycf4 that can be used as specific DNA barcodes to distinguish and identify C. vaginatum, L. sinense, and L. jeholense. In addition, phylogenetic study showed that C. vaginatum nested in Ligusticum and as a sister group of L. sinense and L. jeholense, which suggested these two genera are both in need of revision. This study offer valuable information for future research in the identification of Gaoben-related medicinal materials and will benefit for further phylogenetic study of Apiaceae.

5.
JCI Insight ; 7(10)2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35446788

RESUMO

Bacteria have evolved to cope with the detrimental effects of ROS using their essential molecular components. Catalase, a heme-containing tetramer protein expressed universally in most aerobic bacteria, plays an indispensable role in scavenging excess hydrogen peroxide (H2O2). Here, through use of wild-type and catalase-deficient mutants, we identified catalase as an endogenous therapeutic target of 400-420 nm blue light. Catalase residing inside bacteria could be effectively inactivated by blue light, subsequently rendering the pathogens extremely vulnerable to H2O2 and H2O2-producing agents. As a result, photoinactivation of catalase and H2O2 synergistically eliminated a wide range of catalase-positive planktonic bacteria and P. aeruginosa inside biofilms. In addition, photoinactivation of catalase was shown to facilitate macrophage defense against intracellular pathogens. The antimicrobial efficacy of catalase photoinactivation was validated using a Pseudomonas aeruginosa-induced mouse abrasion model. Taken together, our findings offer a catalase-targeting phototherapy approach against multidrug-resistant bacterial infections.


Assuntos
Peróxido de Hidrogênio , Pseudomonas aeruginosa , Animais , Biofilmes , Catalase/genética , Catalase/metabolismo , Catalase/farmacologia , Peróxido de Hidrogênio/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo
6.
Artigo em Chinês | WPRIM | ID: wpr-927391

RESUMO

OBJECTIVE@#To observe the clinical effect of cluster acupuncture at scalp points in treating limb spasm after stroke on the basis of conventional exercise therapy.@*METHODS@#A total of 72 patients with limb spasm after stroke were randomly divided into an observation group (36 cases, 5 cases dropped off) and a control group (36 cases, 6 cases dropped off). The control group was treated with exercise therapy. In the observation group, on the basis of the control group, penetrating technique of acupuncture was exerted at Qianding (GV 21) to Baihui (GV 20), Xinhui (GV 22) to Qianding (GV 21), etc. once a day, 5 days a week for 4 weeks. Before and after treatment, the changes of the modified Ashworth scale (MAS), simplified Fugl-Meyer motor assessment (FMA), and modified Barthel index (MBI) scores of the two groups were compared.@*RESULTS@#After treatment, the MAS scores of upper and lower limbs in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, the scores of FMA and BMI in the two groups were higher than before treatment (P<0.05), and the score of MBI in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#On the basis of conventional exercise therapy, cluster acupuncture at scalp points can reduce the spasm, improve motor function and activities of daily living in patients with limb spasm after stroke.


Assuntos
Humanos , Atividades Cotidianas , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Terapia por Exercício , Extremidade Inferior , Couro Cabeludo , Espasmo , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral , Resultado do Tratamento
7.
J Zhejiang Univ Sci B ; 22(11): 929-940, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783223

RESUMO

Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress syndrome (ARDS) or even death. Expression of proinflammatory interleukin-|1ß (IL-|1ß) and inducible nitric oxide synthase (iNOS) in the process of pulmonary inflammation will further exacerbate the severity of ALI. The purpose of this study was to explore the effect of Palrnatine (Pa) on lipopolysaccharide (LPS)-induced mouse ALI and its underlying mechanism. Pa, a natural product, has a wide range of pharmacological activities with the potential to protect against lung injury. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to detect the expression and translation of inflammatory genes and proteins in vitro and in vivo. Immunoprecipitation was used to detect the degree of P65 translocation into the nucleus. We also used molecular modeling to further clarify the mechanism of action. The results showed that Pa pretreatment could significantly inhibit the expression and secretion of the inflammatory cytokine IL-1ß, and significantly reduce the protein level of the proinflammatory protease iNOS, in both in vivo and in vitro models induced by LPS. Further mechanism studies showed that Pa could significantly inhibit the activation of the protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway in the LPS-induced ALI mode and in LPS-induced RAW264.7 cells. Through molecular dynamics simulation, we observed that Pa was bound to the catalytic pocket of Akt and effectively inhibited the biological activity of Akt. These results indicated that Pa significantly relieves LPS-induced ALI by activating the Akt/NF-κB signaling pathway.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Menispermaceae/química , NF-kappa B/antagonistas & inibidores , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Simulação de Dinâmica Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
8.
Mol Cell ; 80(6): 1104-1122.e9, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33259812

RESUMO

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.


Assuntos
Células Epiteliais Alveolares/metabolismo , COVID-19/metabolismo , Fosfoproteínas/metabolismo , Proteoma/metabolismo , SARS-CoV-2/metabolismo , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Animais , Antivirais , COVID-19/genética , COVID-19/patologia , Chlorocebus aethiops , Efeito Citopatogênico Viral , Citoesqueleto , Avaliação Pré-Clínica de Medicamentos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/virologia , Fosfoproteínas/genética , Transporte Proteico , Proteoma/genética , SARS-CoV-2/genética , Transdução de Sinais , Células Vero , Tratamento Farmacológico da COVID-19
9.
JCI Insight ; 5(11)2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32493838

RESUMO

With the effectiveness of antimicrobials declining as antimicrobial resistance continues to threaten public health, we must look to alternative strategies for the treatment of infections. In this study, we investigated an innovative, drug-free, dual-wavelength irradiation approach that combines 2 wavelengths of light, 460 nm and 405 nm, against methicillin-resistant Staphylococcus aureus (MRSA). MRSA was initially irradiated with 460-nm light (90-360 J/cm2) and subsequently irradiated with aliquots of 405-nm light (54-324 J/cm2). For in vivo studies, mouse skin was abraded and infected with approximately 107 CFUs of MRSA and incubated for 3 hours before irradiating with 460 nm (360 J/cm2) and 405 nm (342 J/cm2). Naive mouse skin was also irradiated to investigate apoptosis. We found that staphyloxanthin, the carotenoid pigment in MRSA cells, promoted resistance to the antimicrobial effects of 405-nm light. In addition, we found that the photolytic effect of 460-nm light on staphyloxanthin attenuated resistance of MRSA to 405-nm light killing. Irradiation of 460 nm alone did not elicit any antimicrobial effect on MRSA. In a proof-of-principle mouse skin abrasion infection model, we observed significant killing of MRSA using the dual-wavelength irradiation approach. However, when either wavelength of light was administered alone, no significant decrease in bacterial viability was observed. Moreover, exposure of the dual-wavelength irradiation to naive mouse skin did not result in any visible apoptosis. In conclusion, a dual-wavelength irradiation strategy may offer an innovative, effective, and safe approach for the treatment of skin infections caused by MRSA.


Assuntos
Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Fototerapia , Infecções Cutâneas Estafilocócicas , Animais , Modelos Animais de Doenças , Infecções Cutâneas Estafilocócicas/metabolismo , Infecções Cutâneas Estafilocócicas/patologia , Infecções Cutâneas Estafilocócicas/terapia
10.
Adv Sci (Weinh) ; 7(6): 1903117, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195102

RESUMO

Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug-resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin-resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo-disassembly of functional membrane microdomains. The photo-disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore-targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug-resistant S. aureus infections as well as to screen new lead compounds.

11.
J Infect Dis ; 221(4): 618-626, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31565732

RESUMO

BACKGROUND: Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. METHODS: In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. RESULTS: Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. CONCLUSIONS: In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Quinina/uso terapêutico , Terapia Ultravioleta/métodos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/efeitos da radiação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos da radiação , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Plâncton/microbiologia , Pseudomonas aeruginosa/fisiologia , Quinina/farmacologia , Pele/lesões , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Ferimentos e Lesões/microbiologia
12.
J Biomed Opt ; 25(1): 1-11, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31849205

RESUMO

Hemozoin, the heme detoxification end product in malaria parasites during their growth in the red blood cells (RBCs), serves as an important marker for diagnosis and treatment target of malaria disease. However, the current method for hemozoin-targeted drug screening mainly relies on in vitro ß-hematin inhibition assays, which may lead to false-positive events due to under-representation of the real hemozoin crystal. Quantitative in situ imaging of hemozoin is highly desired for high-throughput screening of antimalarial drugs and for elucidating the mechanisms of antimalarial drugs. We present transient absorption (TA) imaging as a high-speed single-cell analysis platform with chemical selectivity to hemozoin. We first demonstrated that TA microscopy is able to identify ß-hematin, the artificial form of hemozoin, from the RBCs. We further utilized time-resolved TA imaging to in situ discern hemozoin from malaria-infected RBCs with optimized imaging conditions. Finally, we quantitatively analyzed the hemozoin amount in RBCs at different infection stages by single-shot TA imaging. These results highlight the potential of TA imaging for efficient antimalarial drug screening and drug mechanism investigation.


Assuntos
Eritrócitos/metabolismo , Hemeproteínas/metabolismo , Microscopia/métodos , Animais , Antimaláricos/farmacologia , Cristalização , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/parasitologia , Hemeproteínas/análise , Hemeproteínas/química , Ensaios de Triagem em Larga Escala , Humanos , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Microscopia Eletrônica de Varredura , Fenômenos Ópticos , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/metabolismo , Análise de Célula Única/métodos
13.
Medicine (Baltimore) ; 98(24): e16006, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192945

RESUMO

BACKGROUND: This study aims to systematically evaluate the effectiveness of rehabilitation training (RT) combined with acupuncture on aphasia after cerebral hemorrhage (CH). METHODS: PUBMED, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, Ovid, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched to identify any potential studies from inception to March 1, 2019, without language restrictions. All randomized controlled trials and case-controlled studies assessing the effectiveness of RT combined with acupuncture for the treatment of aphasia following CH will be included in this study. Cochrane risk of bias tool will be used to determine the methodological quality for included studies. RevMan 5.3 software (Cochrane Community, London, UK) will be utilized to perform statistical analysis. RESULTS: This study will systematically evaluate the effectiveness of RT and acupuncture for aphasia post CH. Primary outcome includes aphasia, which can be measured by Aachener Aphasia Test or Communicative Activity Log or other related scales. Secondary outcomes consist of speech performance, as assessed by Western Aphasia Battery-Revised; measure of skill in Supported Conversation scales; measure of Participation in Conversation scales; types of strategies used in conversation; occurrence and repair of conversation breakdowns; as well as any adverse events. CONCLUSION: The results of this study will provide present evidence on assessing effectiveness of RT and acupuncture after CH. DISSEMINATION AND ETHICS: The findings of this study are expected to be published in peer-reviewed journals. It does not require ethical approval, because no individual data will be utilized in this study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131587.


Assuntos
Afasia/reabilitação , Afasia/terapia , Hemorragia Cerebral/complicações , Terapia por Acupuntura , Afasia/etiologia , China , Terapia Combinada , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do Tratamento
14.
Adv Sci (Weinh) ; 6(11): 1900030, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31179216

RESUMO

Confronted with the severe situation that the pace of resistance acquisition is faster than the clinical introduction of new antibiotics, health organizations are calling for effective approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, an approach to treat MRSA through photolysis of staphyloxanthin, an antioxidant residing in the microdomain of S. aureus membrane, is reported. This photochemistry process is uncovered through transient absorption imaging and quantitated by absorption spectroscopy, Raman spectroscopy, and mass spectrometry. Photolysis of staphyloxanthin transiently elevates the membrane permeability and renders MRSA highly susceptible to hydrogen peroxide attack. Consequently, staphyloxanthin photolysis by low-level 460 nm light eradicates MRSA synergistically with hydrogen peroxide and other reactive oxygen species. The effectiveness of this synergistic therapy is well validated in MRSA planktonic culture, MRSA-infected macrophage cells, stationary-phase MRSA, persisters, S. aureus biofilms, and two mice wound infection models. Collectively, the work demonstrates that staphyloxanthin photolysis is a new therapeutic platform to treat MRSA infections.

15.
Medicine (Baltimore) ; 98(9): e14726, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817621

RESUMO

BACKGROUND: Previous studies have reported that rehabilitation training combined acupuncture (RTA) can be used for the treatment of limb hemiplegia (LH) caused by cerebral hemorrhage (CH). However, its effectiveness is still unclear. In this systematic review study, we aim to evaluate the effectiveness and safety of RTA for LH following CH. METHODS: We will retrieve the databases of CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, CBM, and CNKI from inception to March 1, 2019 with no language restrictions. The randomized controlled trials of RTA for evaluating effectiveness and safety in patients with LH following CH will be included. Cochrane risk of bias tool will be used to measure the methodological quality for all included studies. Two authors will independently select the studies, extract the data, and assess the methodological quality of included studies. A third author will be invited to discuss if any disagreements exist between 2 authors. If more than 2 eligible studies will be included, the outcome data will be pooled, and meta-analysis will be conducted if it is possible. RESULTS: This systematic review will assess the effectiveness and safety of RTA for LH caused by CH. The primary outcome includes limbs function. The secondary outcomes consist of muscle strength, muscle tone, quality of life, and any adverse events. CONCLUSION: The findings of this study will summarize the current evidence of RTA for LH caused by CH, and may provide helpful evidence for the clinical treatment. DISSEMINATION AND ETHICS: The results of this study will be published in peer-reviewed journals or will be presented on conference meeting. This work does not require ethic approval, because it will be conducted based on the published studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019120034.


Assuntos
Terapia por Acupuntura/métodos , Hemorragia Cerebral/complicações , Hemiplegia/etiologia , Hemiplegia/terapia , Modalidades de Fisioterapia , Terapia Combinada , Hemiplegia/reabilitação , Humanos , Força Muscular , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
16.
Artigo em Chinês | WPRIM | ID: wpr-801968

RESUMO

Objective: To discuss the clinical efficacy of modified Da Chengqitang by enema in treatment of postoperative inflammatory intestinal obstruction (EPISBO) after the operation and its effect on inflammatory factors, gastrointestinal motility and intestinal barrier function. Method: One hundred and six patients were randomly divided into control group (52 cases) and observation group (54 cases) by random number table. Patients in both groups were given fasting for solids and liquids, gastrointestinal decompression, maintaining water and electrolyte balance, nutritional support and other basic therapies. Patients in control group were given somatostatin for injection for continuous micro-pumping, 0.003 5 mg·h-1·kg-1, dexamethasone acetate tablets, 2.5-5 mg/time, 2 time/days. Patients with concurrent infection got ceftazidime for injection, 30-100 mg·kg-1, 2-3 intravenous drips. In addition to the therapy of control group, patients in observation group were also given modified Da Chengqitang, 125 mL/time, 2 times/days. A course of treatment was 5 days. Time of remission of abdominal distention, recovery of exhaust gas, bowel sounds and diet, defecation, hospitalization and transitional surgery were recorded. And main gastrointestinal symptoms and signs were scored. And levels of serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), vasoactive intestinal peptide (VIP), gastrin, motilin, diamine oxidase and D lactic acid were detected. Result: After treatment, according to rank sum test analysis, the clinical efficacy in observation group was better than that in control group (PPPPα, hs-CRP, VIP, DAO, D-lactic acid and scores of main gastrointestinal symptoms and signs were all lower than those in control group (PPConclusion: In addition of routine therapy of western medicine, modified Dachengqi Tang had effects in resisting inflammation, regulating gastrointestinal hormones, and protecting intestinal barrier function, so can improve gastrointestinal motility, alleviate symptoms, shorten the course of disease and improve the clinical efficacy.

17.
Cell Mol Biol Lett ; 23: 47, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30305826

RESUMO

BACKGROUND: Evidence has shown that endogenous H2S plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous H2S has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis. METHODS: The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of H2S in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur. RESULTS: The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of H2S in the plasma in one group, designated OVX-GYY during the observation period (p < 0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased (p < 0.05). The BMD femur value in the OVX-vehicle group had decreased (p < 0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all p < 0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all p < 0.05). CONCLUSIONS: Through the slow release of H2S, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous H2S had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.


Assuntos
Morfolinas/uso terapêutico , Compostos Organotiofosforados/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Cálcio/sangue , Modelos Animais de Doenças , Feminino , Hormônios/sangue , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Osteoporose/sangue , Osteoporose/fisiopatologia , Fósforo/sangue , Ratos Sprague-Dawley
18.
Medicine (Baltimore) ; 97(31): e11625, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075540

RESUMO

BACKGROUND: This study assessed the effect transcutaneous vagus nerve stimulation (TVNS) for poststroke epilepsy (PSE). METHODS: Fifty-two patients with PSE were included in this study. Twenty-seven patients received TVNS, 30 minutes each session, once daily, twice weekly for a total of 4 weeks; and were assigned to the treatment group. Twenty-five patients were at waiting list and were assigned to the control group. The primary outcome included weekly seizure frequency. The secondary outcomes consisted of each seizure episode, and quality of life, measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), as well as the adverse events. All outcomes were measured before and after 4-week treatment. RESULTS: After treatment, TVNS failed to show better outcomes in weekly seizure frequency (treatment group, P = .12; control group, P = .56), seizure episode (treatment group, P = .65; control group, P = .92), and QOLIE-31 (treatment group, P = .73; control group, P = .84) compared with these before the treatment. Furthermore, TVNS also did not elaborate the promising effect in seizure frequency (P = .81), seizure episode (P = .75), and QOLIE-31 (P = .33), compared with these in the control group. In addition, minor and acceptable adverse events were recorded in this study. CONCLUSION: The results of this study showed that TVNS may be not effective for Chinese patients PSE after 4-week treatment.


Assuntos
Epilepsia/terapia , Acidente Vascular Cerebral/complicações , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Adulto , Idoso , Epilepsia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Chemphyschem ; 19(19): 2500-2506, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-29911339

RESUMO

Retinoids play critical roles in development, immunity, and lipid metabolism, and their deficiency leads to various human disorders. Yet, tools for sensing retinoids in vivo are lacking, which limits the understanding of retinoid distribution, dynamics and functions in living organisms. Here, using hyperspectral stimulated Raman scattering microscopy, we discover a previously unknown cytoplasmic store of retinoids in Caenorahbditis elegans. Following the temporal dynamics of retinoids, we reveal that their levels are positively correlated with fat storage, and their supplementation slows down fat loss during starvation. We also discover that retinoids promote fat unsaturation in response to high-glucose stress, and improve organism survival. Together, our studies report a new method for tracking the spatiotemporal dynamics of retinoids in living organisms, and suggest the crucial roles of retinoids in maintaining metabolic homeostasis and enhancing organism fitness upon developmental and dietary stresses.


Assuntos
Metabolismo dos Lipídeos , Retinoides/metabolismo , Análise Espectral Raman , Animais , Caenorhabditis elegans , Citoplasma/metabolismo , Longevidade , Lisossomos/metabolismo , Microscopia , Retinoides/química
20.
Artigo em Chinês | WPRIM | ID: wpr-661208

RESUMO

Objective:To learn the depression status of the hospitalized pregnant women in labor and its related influencing factors,and to provide the theoretical basis for exploring depression intervention of the pregnant women in labor.Methods:Self-Rating Depression Scale was used for investigating the depression status of 203 hospitalized pregnant women in labor who were in hospital from November 2014 to May 2015,and the impacts of demographic characteristics,maternal history and physical condition and health care on depression status of hospitalized pregnant women in labor before pregnancy and during pregnancy were analyzed using Logistic regression.Results:Fifty-three people with depressive tendencies were detected among pregnant women in labor,and the positive rate was 26.1%.The differences in positive rates of depression tendency of the pregnant women between less than 30 years,30-39 years and 40 years and above had no statistical significance (P>0.05).Univariate Logistic analysis showed that the differences of occupation,overweight or obesity,low-dose folic acid supplements before pregnancy were statistically significant (P<0.01).Multivariate Logistic regression analysis showed that risk factor for pregnant women was overweight or obesity pre-pregnancy,and the risk was 2.335 times to non-overweight or non-obesity pregnancy women (OR=2.335,95%CI:1.101-4.954,P<0.05).Conclusion:The pregnant women have the depression tendency,especially the pregnant women with high body mass index before pregnancy.The knowledge of psychological health education should be provided for them.

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