High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds.

abstract：:Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we te...

journal_title：Science translational medicine

authors： Wee S,Vendruscolo LF,Misra KK,Schlosburg JE,Koob GF

更新日期：2012-08-08 00:00:00

abstract：:Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circul...

journal_title：Science translational medicine

authors： Larsen R,Gozzelino R,Jeney V,Tokaji L,Bozza FA,Japiassú AM,Bonaparte D,Cavalcante MM,Chora A,Ferreira A,Marguti I,Cardoso S,Sepúlveda N,Smith A,Soares MP

更新日期：2010-09-29 00:00:00

abstract：:Acquired lymphedema is a cancer sequela and a global health problem currently lacking pharmacologic therapy. We have previously demonstrated that ketoprofen, an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory properties, effectively reverses histopathology in experimental lymphedema. We ...

journal_title：Science translational medicine

authors： Tian W,Rockson SG,Jiang X,Kim J,Begaye A,Shuffle EM,Tu AB,Cribb M,Nepiyushchikh Z,Feroze AH,Zamanian RT,Dhillon GS,Voelkel NF,Peters-Golden M,Kitajewski J,Dixon JB,Nicolls MR

更新日期：2017-05-10 00:00:00

abstract：:Protein replacement therapies for rare monogenic diseases have a higher probability of regulatory approval compared with biologics, small molecules, and grant-funded orphan drugs. ...

journal_title：Science translational medicine

authors： Gorzelany JA,de Souza MP

更新日期：2013-03-27 00:00:00

abstract：:Long synthetic peptides (LSPs) have a variety of important clinical uses as synthetic vaccines and drugs. Techniques for peptide synthesis were revolutionized in the 1960s and 1980s, after which efficient techniques for purification and characterization of the product were developed. These improved techniques allowed ...

journal_title：Science translational medicine

authors： Corradin G,Kajava AV,Verdini A

更新日期：2010-09-22 00:00:00

abstract：:Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chro...

journal_title：Science translational medicine

authors： Jiang TY,Pan YF,Wan ZH,Lin YK,Zhu B,Yuan ZG,Ma YH,Shi YY,Zeng TM,Dong LW,Tan YX,Wang HY

更新日期：2020-09-23 00:00:00

abstract：:Chemotherapy-induced cardiotoxicity (CIC) is a common clinical problem that compromises effective anticancer therapies. Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure. Althoug...

journal_title：Science translational medicine

authors： Saleme B,Gurtu V,Zhang Y,Kinnaird A,Boukouris AE,Gopal K,Ussher JR,Sutendra G

更新日期：2019-02-06 00:00:00

abstract：:High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provid...

journal_title：Science translational medicine

authors： Ravà M,D'Andrea A,Nicoli P,Gritti I,Donati G,Doni M,Giorgio M,Olivero D,Amati B

更新日期：2018-01-31 00:00:00

abstract：:Glycogen synthase kinase 3 (GSK3), a key regulatory kinase in the wingless-type MMTV integration site family (WNT) pathway, is a therapeutic target of interest in many diseases. Although dual GSK3α/β inhibitors have entered clinical trials, none has successfully translated to clinical application. Mechanism-based toxi...

journal_title：Science translational medicine

authors： Wagner FF,Benajiba L,Campbell AJ,Weïwer M,Sacher JR,Gale JP,Ross L,Puissant A,Alexe G,Conway A,Back M,Pikman Y,Galinsky I,DeAngelo DJ,Stone RM,Kaya T,Shi X,Robers MB,Machleidt T,Wilkinson J,Hermine O,Kung A,St

更新日期：2018-03-07 00:00:00

abstract：:Pluripotent stem cells are a scalable source of pancreatic cells for transplantation into patients with diabetes. Here, we describe how the field is gaining momentum toward a β cell replacement therapy. ...

journal_title：Science translational medicine

authors： Bruin JE,Rezania A,Kieffer TJ

更新日期：2015-12-02 00:00:00

abstract：:A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinic...

journal_title：Science translational medicine

authors： Roche ET,Fabozzo A,Lee Y,Polygerinos P,Friehs I,Schuster L,Whyte W,Casar Berazaluce AM,Bueno A,Lang N,Pereira MJ,Feins E,Wasserman S,O'Cearbhaill ED,Vasilyev NV,Mooney DJ,Karp JM,Del Nido PJ,Walsh CJ

更新日期：2015-09-23 00:00:00

abstract：:Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced...

journal_title：Science translational medicine

authors： Dakin SG,Martinez FO,Yapp C,Wells G,Oppermann U,Dean BJ,Smith RD,Wheway K,Watkins B,Roche L,Carr AJ

更新日期：2015-10-28 00:00:00

abstract：:Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte-specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-th...

journal_title：Science translational medicine

authors： Asimaki A,Kapoor S,Plovie E,Karin Arndt A,Adams E,Liu Z,James CA,Judge DP,Calkins H,Churko J,Wu JC,MacRae CA,Kléber AG,Saffitz JE

更新日期：2014-06-11 00:00:00

abstract：:Patients with rheumatoid arthritis (RA) may display atypical CD21-/lo B cells in their blood, but the implication of this observation remains unclear. We report here that the group of patients with RA and elevated frequencies of CD21-/lo B cells shows decreased ataxia telangiectasia-mutated (ATM) expression and activa...

journal_title：Science translational medicine

authors： Mensah KA,Chen JW,Schickel JN,Isnardi I,Yamakawa N,Vega-Loza A,Anolik JH,Gatti RA,Gelfand EW,Montgomery RR,Horowitz MC,Craft JE,Meffre E

更新日期：2019-11-20 00:00:00

abstract：:Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rati...

journal_title：Science translational medicine

authors： Wong HR,Caldwell JT,Cvijanovich NZ,Weiss SL,Fitzgerald JC,Bigham MT,Jain PN,Schwarz A,Lutfi R,Nowak J,Allen GL,Thomas NJ,Grunwell JR,Baines T,Quasney M,Haileselassie B,Lindsell CJ

更新日期：2019-11-13 00:00:00

abstract：:KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS mutations have been shown previously to be selectively sensitive to inhibition of mitogen-activated...

journal_title：Science translational medicine

authors： Molina-Arcas M,Moore C,Rana S,van Maldegem F,Mugarza E,Romero-Clavijo P,Herbert E,Horswell S,Li LS,Janes MR,Hancock DC,Downward J

更新日期：2019-09-18 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated wi...

journal_title：Science translational medicine

authors： Smith BN,Topp SD,Fallini C,Shibata H,Chen HJ,Troakes C,King A,Ticozzi N,Kenna KP,Soragia-Gkazi A,Miller JW,Sato A,Dias DM,Jeon M,Vance C,Wong CH,de Majo M,Kattuah W,Mitchell JC,Scotter EL,Parkin NW,Sapp PC,Nol

更新日期：2017-05-03 00:00:00

abstract：:Prenatal and postnatal treatment with a CFTR modifier attenuates pathological changes in a ferret model of cystic fibrosis (Sun et al., this issue). ...

journal_title：Science translational medicine

authors： Ferkol TW

更新日期：2019-03-27 00:00:00

abstract：:Immunological and inflammatory processes downstream of dystrophin deficiency as well as metabolic abnormalities, defective autophagy, and loss of regenerative capacity all contribute to muscle pathology in Duchenne muscular dystrophy (DMD). These downstream cascades offer potential avenues for pharmacological interven...

journal_title：Science translational medicine

authors： Rosenberg AS,Puig M,Nagaraju K,Hoffman EP,Villalta SA,Rao VA,Wakefield LM,Woodcock J

更新日期：2015-08-05 00:00:00

abstract：:Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically ...

journal_title：Science translational medicine

authors： Hoyle NP,Seinkmane E,Putker M,Feeney KA,Krogager TP,Chesham JE,Bray LK,Thomas JM,Dunn K,Blaikley J,O'Neill JS

更新日期：2017-11-08 00:00:00

abstract：:Cardiac rhythm is extremely robust, generating 2 billion contraction cycles during the average human life span. Transcriptional control of cardiac rhythm is poorly understood. We found that removal of the transcription factor gene Tbx5 from the adult mouse caused primary spontaneous and sustained atrial fibrillation (...

journal_title：Science translational medicine

authors： Nadadur RD,Broman MT,Boukens B,Mazurek SR,Yang X,van den Boogaard M,Bekeny J,Gadek M,Ward T,Zhang M,Qiao Y,Martin JF,Seidman CE,Seidman J,Christoffels V,Efimov IR,McNally EM,Weber CR,Moskowitz IP

更新日期：2016-08-31 00:00:00

abstract：:Targeting androgen receptor (AR) axis signaling by disrupting androgen-AR interactions remains the primary treatment for metastatic prostate cancer. Unfortunately, all men develop resistance to primary castrating therapy and secondary androgen deprivation therapies (ADTs). Resistance develops in part because castratio...

journal_title：Science translational medicine

authors： Schweizer MT,Antonarakis ES,Wang H,Ajiboye AS,Spitz A,Cao H,Luo J,Haffner MC,Yegnasubramanian S,Carducci MA,Eisenberger MA,Isaacs JT,Denmeade SR

更新日期：2015-01-07 00:00:00

abstract：:About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral b...

journal_title：Science translational medicine

authors： Maldonado L,Teague JE,Morrow MP,Jotova I,Wu TC,Wang C,Desmarais C,Boyer JD,Tycko B,Robins HS,Clark RA,Trimble CL

更新日期：2014-01-29 00:00:00

abstract：:Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mous...

journal_title：Science translational medicine

authors： Askew C,Rochat C,Pan B,Asai Y,Ahmed H,Child E,Schneider BL,Aebischer P,Holt JR

更新日期：2015-07-08 00:00:00

abstract：:Despite the very low risk-to-benefit ratio of vaccines, fear of negative side effects has discouraged many people from getting vaccinated, resulting in reemergence of previously controlled diseases such as measles, pertussis, and diphtheria. Part of this fear stems from the lack of public awareness of the many preclin...

journal_title：Science translational medicine

authors： Ahmed SS,Plotkin SA,Black S,Coffman RL

更新日期：2011-07-27 00:00:00

abstract：:SORLA/SORL1 is a unique neuronal sorting receptor for the amyloid precursor protein that has been causally implicated in both sporadic and autosomal dominant familial forms of Alzheimer's disease (AD). Brain concentrations of SORLA are inversely correlated with amyloid-β (Aβ) in mouse models and AD patients, suggestin...

journal_title：Science translational medicine

authors： Caglayan S,Takagi-Niidome S,Liao F,Carlo AS,Schmidt V,Burgert T,Kitago Y,Füchtbauer EM,Füchtbauer A,Holtzman DM,Takagi J,Willnow TE

更新日期：2014-02-12 00:00:00

abstract：:Macrophages in the healthy intestine are highly specialized and usually respond to the gut microbiota without provoking an inflammatory response. A breakdown in this tolerance leads to inflammatory bowel disease (IBD), but the mechanisms by which intestinal macrophages normally become conditioned to promote microbial ...

journal_title：Science translational medicine

authors： Scott NA,Andrusaite A,Andersen P,Lawson M,Alcon-Giner C,Leclaire C,Caim S,Le Gall G,Shaw T,Connolly JPR,Roe AJ,Wessel H,Bravo-Blas A,Thomson CA,Kästele V,Wang P,Peterson DA,Bancroft A,Li X,Grencis R,Mowat AM,Hal

更新日期：2018-10-24 00:00:00

abstract：:In populations that have not been selected for family history of disease, it is unclear how commonly pathogenic variants (PVs) in disease-associated genes for rare Mendelian conditions are found and how often they are associated with clinical features of these conditions. We conducted independent, prospective analyses...

journal_title：Science translational medicine

authors： Natarajan P,Gold NB,Bick AG,McLaughlin H,Kraft P,Rehm HL,Peloso GM,Wilson JG,Correa A,Seidman JG,Seidman CE,Kathiresan S,Green RC

更新日期：2016-11-09 00:00:00

abstract：:Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth ag...

journal_title：Science translational medicine

authors： Julg B,Tartaglia LJ,Keele BF,Wagh K,Pegu A,Sok D,Abbink P,Schmidt SD,Wang K,Chen X,Joyce MG,Georgiev IS,Choe M,Kwong PD,Doria-Rose NA,Le K,Louder MK,Bailer RT,Moore PL,Korber B,Seaman MS,Abdool Karim SS,Morris

更新日期：2017-09-06 00:00:00

abstract：:In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center ...

journal_title：Science translational medicine

authors： Bachmann LC,Matis A,Lindau NT,Felder P,Gullo M,Schwab ME

更新日期：2013-10-23 00:00:00