Ling-Ling Hwang

Taipei Medical University | TMU · Department of Physiology

Background Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events. Materials and methods We used behavioral testing, Western...

Background/Purpose Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-fre...

Traumatic brain injury (TBI) is a global health issue that affects at least 10 million people per year. Neuronal cell death and brain injury after TBI, including apoptosis, inflammation, and excitotoxicity, have led to detrimental effects in TBI. 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a water-soluble compound extracted from t...

Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using...

Background/aim: Central administration of cocaine- and amphetamine-regulated transcript peptides (CARTp) alters gastrointestinal motility and reduces food intake in rats. Since neurons in the dorsal motor nucleus of the vagus (DMV) receive GABAergic and glutamatergic inputs and innervate the smooth muscle of gastrointestinal organs, we hypothesize...

The dorsomedial hypothalamus (DMH) receives dense orexinergic innervation. Intra-DMH application of orexins increases arterial pressure and heart rate in rats. We studied the effects of orexin-A on DMH neurons, including those innervating the medullary cardiovascular center, the rostral ventrolateral medulla (RVLM), by using whole-cell recordings i...

It was highlighted that the original article [1] contained the wrong Fig. 1.

The paraventricular nucleus of the hypothalamus (PVN) contains dense orexin 2 (OX2) receptor. We examined the mechanisms of OX2 receptor-mediated excitation on electrophysiologically identified type I (putative magnocellular), low-threshold spikes (LTS)-expressing type II (putative preautonomic), and non-LTS type II (putative parvocellular neuroend...

Background: Gold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40-50 nm) collapsed endothelial tight junct...

Significance Pain remains an unmet medical need due to the ineffectiveness or significant side effects of current pain therapies. Peripheral neurostimulation has been used to relieve pain for decades, but its mechanism(s) remain unsettled. Here, we established an animal model of median nerve stimulation by electrically stimulating the PC6 (Neiguan)...

Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics comp...

Hypertensive subjects often exhibit exaggerated cardiovascular reactivity. An overactive orexin system underlies the pathophysiology of hypertension. We examined orexin's roles in eating-associated cardiovascular reactivity in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Results showed eating regular chow or palatable food (s...

Background/aims: Hyperlipidemia induces dysfunction in the smooth muscle cells (SMCs) of the blood vessels, and the vascular remodeling that ensues is a key proatherogenic factor contributing to cardiovascular events. Chemokines and chemokine receptors play crucial roles in vascular remodeling. Here, we examined whether the hyperlipidemia-derived...

Orexins are important regulators of cardiovascular functions in various physiological and pathological conditions. The dorsomedial hypothalamus (DMH), an essential mediator of cardiovascular responses to stress, contains dense orexinergic innervations and receptors. We examined whether orexins can regulate cardiovascular functions through their act...

Orexins are associated with drug relapse in rodents. Here, we show that acute restraint stress in mice activates lateral hypothalamic (LH) orexin neurons, increases levels of orexin A and 2-arachidonoylglycerol (2-AG) in the ventral tegmental area (VTA), and reinstates extinguished cocaine-conditioned place preference (CPP). This stress-induced rei...

Supplementary Figures 1-5, Supplementary Table 1

The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic st...

The orexin system consists of orexin A/hypocretin 1 and orexin B/hypocretin 2, and OX1 and OX2 receptors. Our previous electrophysiological study showed that orexin A in the rat ventrolateral periaqueductal gray (vlPAG) induced antinociception via an OX1 receptor-initiated and endocannabinoid-mediated disinhibition mechanism. Here, we further chara...

Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergi...

In current health examination setting, people frequently undergo heart rate variability (HRV) analysis and colonoscopy on the same day. However, it remains unclear whether the bowel preparation before colonoscopy affects HRV. This study aimed to evaluate the association between HRV and bowel preparation. We conducted a cross-sectional observational...

Previous study showed that elevated orexin 2 receptor (OX2R) activity within rostral ventrolateral medulla (RVLM) contributes to hypertension in spontaneously hypertensive rats (SHR). Herein, we investigated the mechanism(s) underlying the elevated OX2R activity. The following results were found. (1) More hypothalamic orexin A-immunoreactive (OXA-I...

New Findings What is the central question of this study? Central orexinergic activity is involved in tonic and phasic control of cardiovascular homeostasis. A potential role for elevated central orexinergic activity in the maintenance of hypertension in spontaneously hypertensive rats (SHRs) has not previously been explored. What is the main findin...

We have demonstrated previously that focal adhesion kinase (FAK)/RhoA alteration by the aryl-hydrocarbon receptor (AhR) agonist 3-methylcholanthrene (3MC) is involved in the antimigratory effects of 3MC in human umbilical vascular endothelial cells. Here, we identified that signaling properties and molecular mechanisms of RhoA/β-catenin were both i...

Gastric cancer is one of the leading causes of cancer mortality and its malignancy, resulting from disseminated cancer cells of diffuse type, is clinically manifested as metastases to the liver and peritoneum. The aim of the present study was to identify putative tumor metastasis-associated genes in human gastric cancer cells of diffuse type. An MK...

Orexin A and B (hypocretin 1 and 2) are novel hypothalamic peptides and two receptor subtypes, OXjR and OX2 R, were identified. Orexins are implicated in hyper-phagia, arousal, and neuroendocrine and auto-nomic regulations. Recently, orexins were found to be antinociceptive supraspinally and spinally but sympathetically stimulating. This review sum...

Previous studies have shown that vascular endothelium-derived matrix metalloproteinases (MMPs) contribute to the destabilization of atherosclerotic plaques, a key event triggering acute myocardial infarction. In addition, studies have reported that the PKC-MEK-PPARγ signaling pathway is involved in oxidized low-density lipoprotein (oxLDL)-induced e...

Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered paclitaxel treating metastases of loca...

BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins...

An injection of orexin A or B into the cisterna magna or the rostral ventrolateral medulla (RVLM), where bulbospinal vasomotor neurons are located, elevated arterial pressure (AP) and heart rate (HR). We examined how orexins affected RVLM neurons to regulate cardiovascular functions by using in vitro recordings of neuronal activity of the RVLM and...

Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4. In vitro/in vivo models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude mice, and murine leukemia cells-inoculated mice were utilized to evaluate BPR0L075 for antiangiogenic and antitumoral activity spectra. BPR0L075...

Physiological and behavioral circadian rhythmicities are exhibited by all mammals and are generated by intracellular levels of circadian oscillators, which are composed of transcriptional/translational feedback loops involving a set of circadian-clock genes, such as Clock, Per1-3, Cry1-2, Bmal1, Dbp, E4BP4 and CK1varepsilon. These circadian-clock g...

Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained...

Immunoreactivity of leptin receptor (Ob-R) has been detected in rat dorsal motor nucleus of the vagus (DMNV). Here, we confirmed the presence of Ob-R immunoreactivity on retrograde-labeled parasympathetic preganglionic neurons in the DMNV of neonatal rats. The present study investigated the effects of leptin on DMNV neurons, including parasympathet...

• Whole-cell patch-clamp recordings were made from neurones of the dorsal motor nucleus of the vagus (DMNV), including Fluoro-gold-labelled parasympathetic preganglionic neurones (PPNs), in slices of the rat medulla. In the latter case, rats had received ani.p.injection of Fluoro-gold solution (10 g) 2-3 days earlier. • Superfusion of orexin A or...

Interrelationships between energy homeostasis and regulation of cardiovascular functions have been suggested by previous observations [Am. J. Physiol. 278 (2000) R692; Regul. Pept. 104 (2002) 75; Am. J. Physiol. 277 (1999) R1780]. Cocaine- and amphetamine-regulated transcript (CART) was first discovered in the striatum of rats treated with cocaine...

Interrelationships between energy homeostasis and regulation of cardiovascular functions have been suggested by previous observations [Am. J. Physiol. 278 (2000) R692; Regul. Pept. 104 (2002) 75; Am. J. Physiol. 277 (1999) R1780]. Cocaine- and amphetamine-regulated transcript (CART) was first discovered in the striatum of rats treated with cocaine...

Angiogenesis plays a major role in many physiological and pathological processes. Pathological development of diseased conditions like growth and metastasis of solid tumors and psoriasis is associated with angiogenesis. Assays developed, thus far, for evaluation of angiogenesis activity are qualitative or semiquantitative. In vivo angiogenesis assa...

Orexin A and B (hypocretin 1 and 2) are the endogenous ligands of orexin receptors, a G-protein-coupled orphan receptor family containing orexin 1 (OX1) and orexin 2 (OX2) types. Orexin A induces analgesia in acute and inflammatory pain models. We further elucidated the possible antiallodynic effect of intrathecal orexins in a rat model of postoper...

1. Whole‐cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1–1 μmol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone (1 μmol/L) insensitive. 2. Nocicept...

Orexin A and B, also known as hypocretin 1 and 2, are two recently isolated hypothalamic peptides. As orexin-containing neurons are strategically located in the lateral hypothalamus, which has long been suspected to play an important role in feeding behaviors, initial studies were focused on the involvement of orexins in positive food intake and en...

Orexin A and B, two recently isolated hypothalamic peptides, have been reported to increase food consumption upon intracerebroventricular injections in rats. In addition to the hypothalamus, orexin A-immunoreactive fibers have been observed in several areas of the medulla that are associated with cardiovascular functions. The present study was unde...

1. Whole-cell patch-clamp recordings were made from rostral ventrolateral medulla (RVLM) neurones of brainstem slices from 8- to 12-day-old rats. In the presence of tetrodotoxin (0.5 microM), 5-HT (50 microM) elicited an outward current (I5-HT,outward) (10/44 neurones) associated with an increase in membrane conductance, and an inward current (I5-H...

Patch-clamp recordings in whole-cell configuration were made from ventrolateral medulla neurons of brainstem slices from 8-12-day-old rats. 5-Hydroxytryptamine (3-30 microM) concentration-dependently suppressed excitatory and inhibitory postsynaptic currents evoked by focal stimulation. An augmentation of inhibitory synaptic currents by 5-hydroxytr...

Whole cell patch recordings were made from rostral ventrolateral medullar (RVLM) neurons of brain-stem slices from 8- to 12-day-old rats. By superfusion or pressure ejection to RVLM neurons, 5-hydroxytryptamine (5-HT) elicited three types of membrane potential changes: a slow hyperpolarization (5-HTH), a slow depolarization (5-HTD) and a biphasic r...

Immunohistochemical techniques were used to localize nociceptin-like immunoreactivity (NOCI-LI) in the rat spinal cords. NOCI-LI nerve fibers were distributed in three fairly well-define regions: superficial layers of the dorsal horn, central canal area, and intermediolateral cell column (ILp) of lower cervical, thoracic, upper lumbar, and sacral s...

Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals surrounding many of the postganglionic neurons of the superior cervical, stellate, paravertebral chain ganglia, coeliac/supe...

Mastoparan B (MP-B) is a cationic tetradecapeptide isolated from the black-bellied hornet (Vespa basalis) venom. It has a primary structure (LKLKSIVSWAKKVL-CONH2) distinct from other vespine mastoparans. The peptide caused a dose-dependent swelling in rat hind paw and showed a potent hemolytic activity in guinea pig red blood cells. Studies on the...

Mastoparan B (MP-B) is a cationic tetradecapeptide (LKLKSIVSWAKKVL-CONH2, mol. wt 1611) isolated from the black-bellied hornet (Vespa basalis) venom. The small peptide itself was capable of inducing antibodies without prior conjugation to a protein carrier in rabbits and mice. The mouse antibody was found to be of IgG1 isotype with κ-type light cha...

Neurons in the laterodorsal tegmental nucleus (LDTg), ventrolateral dorsal tegmental nucleus (LDTgV), pedunculopontine tegmental nucleus (PPTg), lateral and medial parabrachial nuclei (LPB and MPB) were immunoreactive to brain nitric oxide synthase (NOS) or isoform I. Double-labeling experiments showed that very few NOS-containing neurons in the po...

Mastoparan B is a cationic, amphiphilic tetradecaeptide (LKLKSIVSWAKKVL-CONH2) isolated from the venom of the hornet Vespa basalis. Intravenous injection of the peptide into rats caused a profound depression of blood pressure and cardiac function, which was inhibited by cyproheptadine, reserpine and multiple doses of compound 48/80, but not by diph...

The lethal protein of the hornet (Vespa basalis) venom is a phospholipase A1 toxin (mol. wt approximately 32,000) with a potent hemolytic activity. Subplantar injection of the toxin caused a dose-dependent swelling in the rat hind paw. Its potency was higher than those of phospholipases A2 and cardiotoxin from cobra venoms. Hind-paw edema induced b...

By gel filtration on a Fractogel TSK HW 50 column followed by cation-exchange chromatography on CM-Trisacryl M, a tetradecapeptide amide, designated 'mastoparan B', was purified from the venom of the hornet Vespa basalis. Its amino acid sequence was determined as: Leu-Lys-Leu-Lys-Ser-Ile-Val-Ser-Trp-Ala-Lys-Lys-Val-Leu-NH2 and its molecular mass wa...

The black-bellied hornet, Vespa basalis, is one of the most dangerous species of wasp in Taiwan. The hornet venom possesses a potent edema-inducing activity in addition to its lethal cardiovascular effect. Rat hind-paw edema induced by the venom was inhibited significantly by antiserotonin compounds (cyproheptadine and methysergide) but not by anti...

The effects of Mn2+, neomycin and four organic Ca2(+)-channel antagonists (OCA): nicardipine, nifedipine, diltiazem and verapamil on the neuromuscular blocking activities of tubocurarine, succinylcholine (SCh), decamethonium and neomycin were studied in isolated mouse phrenic nerve-diaphragm preparations. The effective concentration of SCh for 50%...

The effects of substituting the enkephalin moiety of dynorphin with the dermorphin sequence were studied on the receptor preference, analgesic, and peripheral opioid potencies by using synthetic dermorphin-dynorphin hybrid peptides as the probe. Replacement of the enkephalin moiety of dynorphin with the dermorphin or dermorphin1-5 sequences caused...

1. The interactions of alpha-bungarotoxin or tubocurarine with the neuromuscular block and endplate depolarization induced by succinylcholine (SCh) in the phrenic nerve-diaphragm preparation of mice were studied in order to elucidate the role of depolarization by SCh in the neuromuscular blockade. 2. The SCh concentrations required to depress the i...

The effects of nicardipine, a dihydropyridine Ca2(+)-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 microM), but not nifedipine (100 microM), induced neuromuscular block, fade of tetanic contraction,...