Biology subjects

Bai, S.

Publications and source records attributed to Bai, S..

59 records · Page 4Linked to original sources

bioRxiv2019

NFATC4 Promotes Quiescence and Chemotherapy Resistance in Ovarian Cancer

Development of chemotherapy resistance is a major problem in ovarian cancer. One understudied mechanism of chemoresistance is the induction of quiescence, a reversible non-proliferative state. Unfortunately, little is known about regulators of quiescence. Here we identify the master transcription factor NFATC4 as a regulator of quiescence in ovarian cancer. NFATC4 is enriched in ovarian cancer stem-like cells (CSC) and correlates with decreased proliferation and poor prognosis. Treatment of cancer cells with cisplatin results in NFATC4 nuclear translocation and activation of NFATC4 pathway, while inhibition of the pathway increased chemotherapy response. Induction of NFATC4 activity results in a marked decrease in proliferation, G0 cell cycle arrest and chemotherapy resistance, both in vitro and in vivo. Finally, NFATC4 drives a quiescent phenotype in part via downregulation of MYC. Together these data identify that NFATC4 as a driver of quiescence and a potential new target to combat chemoresistance in ovarian cancer.

cancer biology↗

bioRxiv2019

Selective Activation of TASK-3-containing K+ Channels Reveals Their Therapeutic Potentials in Analgesia

The paucity of selective agonists for TASK-3, a member of two-pore domain K+ (K2P) channels, has contributed to our limited understanding of its biological functions. By targeting a novel druggable transmembrane cavity using a structure-based drug design approach, we discovered a biguanide compound, CHET3, as a highly selective allosteric activator for TASK-3-containing K2P channels, including TASK-3 homomer and TASK-3/TASK-1 heteromer. CHET3 displayed unexpectedly potent analgesic effects in vivo in a variety of acute and chronic pain models in rodents that could be abolished by pharmacology or genetic ablation of TASK-3. We further found that TASK-3-containing channels anatomically define a unique subset population of small-sized, TRPM8, TRPV1 or tyrosine hydroxylase-positive nociceptive sensory neurons and functionally regulate their membrane excitability, supporting CHET3 analgesia in thermal hyperalgesia and mechanical allodynia under chronic pain. Overall, our proof-of-concept study reveals TASK-3-containing K2P channels as a novel druggable target for treating pain.\n\nOne Sentence SummaryIdentification of a novel drug target and its new hit compounds for developing new-generation non-opioid analgesics.

pharmacology and toxicology↗

bioRxiv2018

Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey

Until the late 20th Century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of the vertical meridian of the visual field labelled few or no cells in auditory cortex. We also placed 8 retrograde tracer injections involving core, belt and parabelt auditory areas, none of which revealed direct projections from V1. These results confirm the existence of a direct, nonreciprocal projection from auditory areas to V1 in a different primate species, which has evolved separately from the macaque for over 30 million years. The essential similarity of these observations between marmoset and macaque indicate that early-stage audiovisual integration is a shared characteristic of primate sensory processing.

neuroscience↗

bioRxiv2018

Histone deacetylase HDA19 affects cortical cell fate by interacting with SCARECROW in the Arabidopsis root

Abstract/SummaryThe Arabidopsis root epidermis is a simple model for investigating cell fate specification and pattern formation. In addition to regulatory networks consisting of transcription factors, histone deacetylases are also involved in the cellular patterning process. Here we report HDA19 affects the root epidermal cellular pattern through regulation of cortical cell fate by interacting with SCARECROW. This work reveals two new components in cortical cell specification and uncovers a new facet of SCR function.

plant biology↗

bioRxiv2017

A novel method for estimating LDC levels: total cholesterol and non-HDLC can be used to predict the normal LDLC level in apparently healthy population

BackgroundTriglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) are usually ordered together to test lipid metabolism in physical examination and clinical application. LDLC is a component of TC and its change is closely correlated to TC.\n\nObjectiveWe aim to predict the normal LDLC level by using TG, TC, HDLC and non-HDLC (nonHDLC) in this study.\n\nMethodsTG, TC, HDLC, and LDLC data were obtained from Laboratory Information System (LIS) based on 4 years (Octo, 1, 2013-Sept, 30, 2017) period health check-up TG, TC, HDLC, and LDLC(direct clearance method) were measured using TBA2000FR biochemical analyzer. The nonHDLC was calculated with TC minus HDLC. Correlation between TG, TC, nonHDLC, and LDLC were analyzed using Spearmans rank approach. Receiver operating characteristics curve analysis was used to evaluate the predictive of TG, TC and nonHDLC for the normal LDLC level(less than 130mg/dL).\n\nResultsBoth TC(r = 0.870) and nonHDLC (r = 0.893) were significantly positively correlated with LDLC. Area under curve of TC and nonHDLC can be used to predict normal LDLC level. Optimal thresholds were 182.5 mg/dL(4.72 mmol/L) for TC and 135.3 mg/dL(3.50 mmol/L) for nonHDLC. Based on these optimal thresholds, less than 0.5% and 0.4% of tests with elevated LDLC might be missed, but the missing elevated LDLC is not too high(less than 147.3 mg/dL).\n\nConclusionIf the nonHDLC is less than 135.3mg/dL(3.50 mmol/L) and/or TC is less than 182.5mg/dL(4.72 mmol/L) for the apparently healthy populations the LDLC level will be less than 130mg/dL(3.36 mmol/L). Total cholesterol and non-HDLC can be used to predict the normal LDLC level in apparently healthy population is a novel method for estimating LDC level.

biochemistry↗