Biology subjects

Hsu, S.-J.

Publications and source records attributed to Hsu, S.-J..

5 recordsLinked to original sources

bioRxiv2025

Liver Lymphatic Dysfunction as a Driver of Fibrosis and Cirrhosis Progression

The liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient lymphatic drainage is essential for liver homeostasis, but its role in liver disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates for increased lymph production, but impaired lymphatic drainage in advanced stages may lead to complications such as ascites and portal hypertension. This study aimed to evaluate how liver lymphatic dysfunction affects disease progression and to assess therapeutic strategies. Using a surgical model to block liver lymphatic outflow, we found that impaired drainage accelerates liver injury, fibrosis, and immune cell infiltration, even in healthy livers. Mechanistically, enhanced TGF-{beta} signaling in liver lymphatic endothelial cells (LyECs) contributed to reduced lymphatic vessel (LV) density and function in late-stage decompensated cirrhosis. This dysfunction was linked to the progression from compensated to decompensated cirrhosis, particularly in patients with primary sclerosing cholangitis (PSC). Conversely, liver-specific overexpression of VEGF-C via AAV8 improved lymphatic drainage, restored LV density, reduced fibrosis, mitigated liver injury, and alleviated portal hypertension in cirrhotic rats. These findings establish impaired liver lymphatic function as a pivotal driver of cirrhosis progression and identify VEGF-C as a promising therapeutic target to prevent decompensation.

pathology↗

bioRxiv2020

Enhanced meningeal lymphatic drainage ameliorates neuroinflammation and hepatic encephalopathy in cirrhotic rats

Background and aimsHepatic encephalopathy (HE) is a serious neurological complication in patients with liver cirrhosis. Nothing is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE. MethodsA 4-week bile duct ligation (BDL) model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated using archived GSE41919. Motor function of rats was assessed by the rotarod test. AAV8-VEGF-C was injected into the cisterna magna of BDL rats one day after surgery to induce meningeal lymphangiogenesis. ResultsCirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (p<0.001) as well as increased neuroinflammation as indicated by significant increases in IL-1{beta}, INF{gamma}, TNF and Iba1 expression in at least one of the three regions of the cortex. Motor function was also impaired in rats with HE (p<0.05). Human brains of cirrhotic patients with HE also exhibited upregulation of pro-inflammatory genes (NF-{kappa}{beta}, Iba1, TNF and IL-1{beta}) (n=6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (p=0.035) and tracer dye uptake in the anterior and middle regions of the cortex (p=0.006 & 0.003, respectively), their corresponding meninges (p=0.086 & 0.006, respectively) and the draining lymph nodes (p=0.02). Further, AAV8-VEGF-C decreased microglia activation (p<0.001) and neuroinflammation, and ameliorated motor dysfunction (p=0.024). ConclusionPromoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.

neuroscience↗

bioRxiv2019

Visual speed compensation of pitch-constrained blue-bottle flies under retinal-image velocity perturbation in a flight mill

In the presence of wind or background image motion, flies are able to maintain a constant retinal-image velocity via regulating flight speed to the extent permitted by their locomotor capacity. Here we investigated the speed regulation of semi-tethered blue-bottle flies (Calliphora vomitoria) flying along an annular corridor in a magnetically levitated flight mill enclosed by two motorized cylindrical walls. We perturbed the flies retinal-image motion via spinning the cylindrical walls, generating bilaterally-averaged velocity perturbations from -0.3 to 0.3 m{middle dot}s-1. Flies compensated retinal-image velocity perturbations by adjusting airspeed up to 20%, thereby maintaining a relatively constant retinal-image velocity. When the retinal-image velocity perturbation became greater than [~]0.1 m{middle dot}s-1, the compensation weakened as airspeed plateaued, suggesting that flies were unable to further change airspeed. The compensation gain, i.e., the ratio of airspeed compensation and retinal-image velocity perturbation, depended on the spatial frequency of the grating patterns, being the largest at 12 m-1.

bioengineering↗

bioRxiv2019

Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

Chromatin insulator proteins mediate the formation of contacts between distant insulator sites along chromatin fibers. Long-range contacts facilitate communication between regulatory sequences and gene promoters throughout the genome, allowing accurate gene transcription regulation during embryo development and cell differentiation. Lack of insulator function has detrimental effects often resulting in lethality. The Drosophila insulator protein Suppressor of Hairy wing [Su(Hw)] is not essential for viability, but plays a crucial role in female oogenesis. The mechanism(s) by which Su(Hw) promotes proper oogenesis remains unclear. To gain insight into the functional properties of chromatin insulators, we further characterize the oogenesis phenotypes of su(Hw) mutant females. We find that mutant egg chambers frequently display an irregular number of nurse cells, have poorly formed microtubule organization centers (MTOC) in the germarium, and show mislocalized Gurken (Grk) in later stages of oogenesis. Furthermore, eggshells produced by partially rescued su(Hw) mutant females exhibit dorsoventral patterning defects that are identical to defects found in spindle mutants or in piRNA pathway mutants. Further analysis reveals an excess of DNA damage in egg chambers, which is independent of activation of transposable elements, and that Gurken localization defects and oogenesis progression are partially rescued by mutations in mei-41 and chk1 genes. In addition, we show that Su(Hw) is required for chromosome integrity in dividing neuroblasts from larval brains. Together, these findings suggest that Su(Hw) plays a critical role in maintaining genome integrity during germline development in Drosophila females as well as in dividing somatic cells.

developmental biology↗

bioRxiv2018

Speed Control and Force-Vectoring of Blue Bottle Flies in a Magnetically-Levitated Flight Mill

Flies fly at a broad range of speeds and produce sophisticated aerial maneuvers with precisely controlled wing movements. Remarkably, only subtle changes in wing motion are used by flies to produce aerial maneuvers, resulting in little directional tilt of aerodynamic force vector relative to the body. Therefore, it is often considered that flies fly according to a helicopter model and control speed mainly via force-vectoring enabled primarily by body-pitch change. Here we examine the speed control of blue bottle flies using a magnetically-levitated (MAGLEV) flight mill, as they fly at different body pitch and with different augmented aerodynamic damping. We identify wing kinematic contributors to the changes of estimated aerodynamic force through testing two force-vectoring models. Results show that in addition to body pitch, flies also use a collection of wing kinematic variables to control both force magnitude and direction, the roles of which are analogous to those of throttle, collective and cyclic pitch of helicopters. Our results also suggest that the MAGLEV flight mill system can be potentially used to study the roles of visual and mechanosensory feedback in insect flight control.\n\nSummary statement: This paper elucidates how files control flight speed while flying in a magnetically-levitated (MAGLEV) flight mill, which enables the manipulation of body pitch and aerodynamic load.

bioengineering↗