[Research Articles] Plasma exosomal miR-375-3p regulates mitochondria-dependent keratinocyte apoptosis by targeting XIAP in severe drug-induced skin reactions
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced cutaneous reactions characterized by keratinocyte apoptosis. Exosomes are nanometer-sized membranous vesicles in body fluids. They contain functional proteins, mRNAs, and miRNAs, which induce immune dysfunction and influence disease progression. However, their roles and mechanisms in SJS/TEN remain unknown. Our results demonstrate that exosomes isolated from the plasma of patients with SJS/TEN were 30 to 200 nm in diameter and expressed CD9, CD63, CD81, and TSG101 exosome marker proteins. miR-375-3p was markedly up-regulated in 35 p...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Zhang, C., Zhu, Z., Gao, J., Yang, L., Dang, E., Fang, H., Shao, S., Zhang, S., Xiao, C., Yuan, X., Li, W., Abe, R., Qiao, H., Wang, G., Fu, M. Tags: Research Articles Source Type: research
[Research Articles] Targeting therapy-resistant prostate cancer via a direct inhibitor of the human heat shock transcription factor 1
This study reports the identification and validation of a direct HSF1 inhibitor and provides a path for the development of a small-molecule HSF1-targeted therapy for prostate cancers and other therapy-resistant cancers. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Dong, B., Jaeger, A. M., Hughes, P. F., Loiselle, D. R., Hauck, J. S., Fu, Y., Haystead, T. A., Huang, J., Thiele, D. J. Tags: Research Articles Source Type: research
[Research Articles] Wireless sensors for continuous, multimodal measurements at the skin interface with lower limb prostheses
Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions of increased pressure and temperature as limb volume changes during daily activities. Conventional pressure transducers and temperature sensors cannot provide comfortable, irritation-free measurements because of their relatively rigid construction and requirements for wired interfaces to external data acquisit...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Kwak, J. W., Han, M., Xie, Z., Chung, H. U., Lee, J. Y., Avila, R., Yohay, J., Chen, X., Liang, C., Patel, M., Jung, I., Kim, J., Namkoong, M., Kwon, K., Guo, X., Ogle, C., Grande, D., Ryu, D., Kim, D. H., Madhvapathy, S., Liu, C., Yang, D. S., Park, Y., Tags: Research Articles Source Type: research
[Reports] Lung transplantation for patients with severe COVID-19
Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19–associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonreso...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Bharat, A., Querrey, M., Markov, N. S., Kim, S., Kurihara, C., Garza-Castillon, R., Manerikar, A., Shilatifard, A., Tomic, R., Politanska, Y., Abdala-Valencia, H., Yeldandi, A. V., Lomasney, J. W., Misharin, A. V., Budinger, G. R. S. Tags: Reports Source Type: research
[Research Articles] Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimers disease pathogenesis
Regulation of glial activation and neuroinflammation are critical factors in the pathogenesis of Alzheimer’s disease (AD). YKL-40, a primarily astrocytic protein encoded by the gene Chi3l1, is a widely studied cerebrospinal fluid biomarker that increases with aging and early in AD. However, the function of Chi3l1/YKL-40 in AD is unknown. In a cohort of patients with AD, we observed that a variant in the human CHI3L1 gene, which results in decreased CSF YKL-40 expression, was associated with slower AD progression. At baseline, Chi3l1 deletion in mice had no effect on astrocyte activation while modestly promoting micro...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Lananna, B. V., McKee, C. A., King, M. W., Del-Aguila, J. L., Dimitry, J. M., Farias, F. H. G., Nadarajah, C. J., Xiong, D. D., Guo, C., Cammack, A. J., Elias, J. A., Zhang, J., Cruchaga, C., Musiek, E. S. Tags: Research Articles Source Type: research
[Research Articles] Mutant huntingtin and neurofilament light have distinct longitudinal dynamics in Huntingtons disease
The longitudinal dynamics of the most promising biofluid biomarker candidates for Huntington’s disease (HD)—mutant huntingtin (mHTT) and neurofilament light (NfL)—are incompletely defined. Characterizing changes in these candidates during disease progression could increase our understanding of disease pathophysiology and help the identification of effective therapies. In an 80-participant cohort over 24 months, mHTT in cerebrospinal fluid (CSF), as well as NfL in CSF and blood, had distinct longitudinal trajectories in HD mutation carriers compared with controls. Baseline analyte values predicted clinical...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Authors: Rodrigues, F. B., Byrne, L. M., Tortelli, R., Johnson, E. B., Wijeratne, P. A., Arridge, M., De Vita, E., Ghazaleh, N., Houghton, R., Furby, H., Alexander, D. C., Tabrizi, S. J., Schobel, S., Scahill, R. I., Heslegrave, A., Zetterberg, H., Wild, E. J. Tags: Research Articles Source Type: research
[Editors' Choice] Quarterly picks from the editors
Four times a year, the Science Translational Medicine editors select recently published articles across the Science family of journals and highlight interesting translational ties. These short write-ups identify common links between disparate diseases; technologies and research approaches that could prove complementary; and biomedical insights that may inform therapies or treatments. This quarter’s articles cover flexible biosensors, SARS-CoV-2 transmission from a genomics perspective, advances in CAR T cell engineering, the intestinal microbiome, the host immune response to SARS-CoV-2, and strategies for treating in...
Source: Science Translational Medicine - December 16, 2020 Category: Biomedical Science Tags: Editors ' Choice Source Type: research
[Editors' Choice] Re-productive brain stimulation
Kisspeptin agonists restore gonadotropin secretion. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Vellanki, P. Tags: Editors ' Choice Source Type: research
[Editors' Choice] Anti-inflammatory drug formulations fight fat
Macrophage-targeted dexamethasone improves weight loss and glucose tolerance not possible with systemic administration of the free drug. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Rodell, C. B. Tags: Editors ' Choice Source Type: research
[Editors' Choice] Convalescent plasma in COVID-19: Does use case matter?
A randomized controlled trial of convalescent plasma in severe COVID-19 shows no benefits. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Nadkarni, G. N. Tags: Editors ' Choice Source Type: research
[Reports] Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy
REVERSE is a randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial that evaluated the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). A total of 37 subjects carrying the m.11778G>A (MT-ND4) mutation and with duration of vision loss between 6 to 12 months were treated. Each subject’s right eye was randomly assigned in a 1:1 ratio to treatment with rAAV2/2-ND4 (GS010) or sham injection. The left eye received the treatment not allocated to the right eye. Unexpectedly, sustained visual improvement was obser...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Yu-Wai-Man, P., Newman, N. J., Carelli, V., Moster, M. L., Biousse, V., Sadun, A. A., Klopstock, T., Vignal-Clermont, C., Sergott, R. C., Rudolph, G., La Morgia, C., Karanjia, R., Taiel, M., Blouin, L., Burguiere, P., Smits, G., Chevalier, C., Masonson, H Tags: Reports Source Type: research
[Reports] Agonist-antagonist myoneural interface amputation preserves proprioceptive sensorimotor neurophysiology in lower limbs
The brain undergoes marked changes in function and functional connectivity after limb amputation. The agonist-antagonist myoneural interface (AMI) amputation is a procedure that restores physiological agonist-antagonist muscle relationships responsible for proprioceptive sensory feedback to enable greater motor control. We compared results from the functional neuroimaging of individuals (n = 29) with AMI amputation, traditional amputation, and no amputation. Individuals with traditional amputation demonstrated a significant decrease in proprioceptive activity, measured by activation of Brodmann area 3a, whereas functional ...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Srinivasan, S. S., Tuckute, G., Zou, J., Gutierrez-Arango, S., Song, H., Barry, R. L., Herr, H. M. Tags: Reports Source Type: research
[Research Articles] Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice
In autosomal dominant conditions with haploinsufficiency, a single functional allele cannot maintain sufficient dosage for normal function. We hypothesized that pharmacologic induction of the wild-type allele could lead to gene dosage compensation and mitigation of the disease manifestations. The paired box 6 (PAX6) gene is crucial in tissue development and maintenance particularly in eye, brain, and pancreas. Aniridia is a panocular condition with impaired eye development and limited vision due to PAX6 haploinsufficiency. To test our hypothesis, we performed a chemical screen and found mitogen-activated protein kinase kin...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Rabiee, B., Anwar, K. N., Shen, X., Putra, I., Liu, M., Jung, R., Afsharkhamseh, N., Rosenblatt, M. I., Fishman, G. A., Liu, X., Ghassemi, M., Djalilian, A. R. Tags: Research Articles Source Type: research
[Research Articles] Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans
Humans are repeatedly exposed to variants of influenza virus throughout their lifetime. As a result, preexisting influenza-specific memory B cells can dominate the response after infection or vaccination. Memory B cells recalled by adulthood exposure are largely reactive to conserved viral epitopes present in childhood strains, posing unclear consequences on the ability of B cells to adapt to and neutralize newly emerged strains. We sought to investigate the impact of preexisting immunity on generation of protective antibody responses to conserved viral epitopes upon influenza virus infection and vaccination in humans. We ...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Dugan, H. L., Guthmiller, J. J., Arevalo, P., Huang, M., Chen, Y.-Q., Neu, K. E., Henry, C., Zheng, N.-Y., Lan, L. Y.-L., Tepora, M. E., Stovicek, O., Bitar, D., Palm, A.-K. E., Stamper, C. T., Changrob, S., Utset, H. A., Coughlan, L., Krammer, F., Cobey, Tags: Research Articles Source Type: research
[Research Articles] Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy
Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Hirai, K., Ousaka, D., Fukushima, Y., Kondo, M., Eitoku, T., Shigemitsu, Y., Hara, M., Baba, K., Iwasaki, T., Kasahara, S., Ohtsuki, S., Oh, H. Tags: Research Articles Source Type: research
