METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.

RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).

RESULTS: Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.

METHOD: Eligible healthy Malay volunteers were invited to undergo the high-resolution esophageal manometry (inSIGHT Ultima, Diversatek Healthcare, Milwaukee, WI, USA). In recumbent and standing positions, test swallows were performed using liquid, viscous, and solid materials. Metrics including integrated relaxation pressure 4 s (IRP-4 s, mmHg), distal contractile integral (DCI, mmHg s cm), distal latency (DL, s), and peristaltic break (PB, cm) were reported in median and 95th percentile.

RESULTS: Fifty of 57 screened participants were recruited, and 586 saline, 265 viscous, and 261 solid swallows were analyzed. Per-patient wise, in the recumbent position, 95th percentile for IRP-4 s, DCI, DL, and PB were 16.5 mmHg, 2431 mmHg s cm, 8.5 s, and 7.2 cm, respectively. We observed that with each posture, the use of viscous swallows led to changes in DL, but the use of solid swallows led to more changes in the metrics including DCI and length of PB. Compared with a recumbent posture, anupright posture led to lower IRP-4 s and DCI values. Both per-patient analysis and per-swallow analyses yielded almost similar results when comparing the different postures and types of swallows. No major motility disorders were observed in this cohort of asymptomatic population. However, more motility disorders were reported in the upright position.