ABSTRACT
We designed and synthesized 27 new amide and dipeptide derivatives containing a substituted phenylalanine as negative allosteric modulators (NAMs) for the beta-2 adrenergic receptor (ß2AR). These analogs aimed to improve the activity of our lead compound, Cmpd-15, by introducing variations in three key regions: the meta-bromobenzyl methylbenzamide (S1), para-formamidophenylalanine (S2), and 1-cyclohexyl-1-phenylacetyl (S3) groups. The synthesis involved the Pd-catalyzed ß-C(sp3)-H arylation of N-acetylglycine with 1-iodo-4-substituent-benzenes as the key step. GloSensor cAMP accumulation assay revealed that six analogs (A1, C5, C6, C13, C15 and C17) surpass Cmpd-15 in ß2AR allosteric function. This highlights the crucial role of the S1 region (meta-bromobenzyl methylbenzamide) in ß2AR allostery while suggesting potential replaceability of the S2 region (para-formamidophenylalanine). These findings serve as a valuable springboard for further optimizing Cmpd-15, potentially leading to smaller, more active, and more stable ß2AR-targeting NAMs.
ABSTRACT
BACKGROUND: Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. AIMS: The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3 years. METHODS: A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. RESULTS: A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. CONCLUSION: Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.
ABSTRACT
Background: adequate bowel preparation is related to the quality of colonoscopy. Dried lemon slices can increase gastrointestinal peristalsis, which has shown potential as an adjuvant of bowel preparation. We hypothesized that the combination of dried lemon slices and polyethylene glycol (PEG) could improve the efficacy of bowel preparation and be more acceptable to participants. Aim: to investigate the effectiveness of lemon slices combined with PEG for colonoscopy preparation. Methods: a prospective, single-center, randomized, controlled trial was performed of 521 patients randomly assigned to two groups. A total of 254 patients were given lemon slices based on conventional 4-L PEG treatment for the bowel, while 267 patients received only 4-L PEG treatment. Patients basic information, procedure-related parameters, adverse effects, and subjective feelings were collected by questionnaires. Intestinal tract cleanliness was scored according to the Boston Bowel Preparation Scale (BBPS) by experienced endoscopists. Data were analyzed by the two-sample t-test or the Chi-squared test. Results: the BBPS scores were significantly higher in the PEG + lemon slice group (p < 0.05). The taste acceptability, satisfaction, and willingness to repeat bowel preparation were significantly higher in the PEG+ lemon slice group (p < 0.05). However, a larger proportion of patients from the PEG+ lemon slice group (30.7 %) suffered abdominal distension compared with the PEG group (20.6 %), while the incidence of other adverse effects was comparable between the two groups. Conclusion: the addition of dried lemon slices to conventional PEG showed its superiority for bowel preparation (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Colonoscopy/methods , Polyethylene Glycols/administration & dosage , Surface-Active Agents/administration & dosage , Treatment Outcome , Socioeconomic FactorsABSTRACT
BACKGROUND: adequate bowel preparation is related to the quality of colonoscopy. Dried lemon slices can increase gastrointestinal peristalsis, which has shown potential as an adjuvant of bowel preparation. We hypothesized that the combination of dried lemon slices and polyethylene glycol (PEG) could improve the efficacy of bowel preparation and be more acceptable to participants. AIM: to investigate the effectiveness of lemon slices combined with PEG for colonoscopy preparation. METHODS: a prospective, single-center, randomized, controlled trial was performed of 521 patients randomly assigned to two groups. A total of 254 patients were given lemon slices based on conventional 4-L PEG treatment for the bowel, while 267 patients received only 4-L PEG treatment. Patients' basic information, procedure-related parameters, adverse effects, and subjective feelings were collected by questionnaires. Intestinal tract cleanliness was scored according to the Boston Bowel Preparation Scale (BBPS) by experienced endoscopists. Data were analyzed by the two-sample t-test or the Chi-squared test. RESULTS: the BBPS scores were significantly higher in the PEG + lemon slice group (p < 0.05). The taste acceptability, satisfaction, and willingness to repeat bowel preparation were significantly higher in the PEG+ lemon slice group (p < 0.05). However, a larger proportion of patients from the PEG+ lemon slice group (30.7 %) suffered abdominal distension compared with the PEG group (20.6 %), while the incidence of other adverse effects was comparable between the two groups. CONCLUSION: the addition of dried lemon slices to conventional PEG showed its superiority for bowel preparation.
Subject(s)
Cathartics , Polyethylene Glycols , Humans , Cathartics/adverse effects , Prospective Studies , Patient Satisfaction , ColonoscopyABSTRACT
Hydrogels usually are fabricated by using monomers or preexisting polymers in precursor solutions. Here, a polyelectrolyte complex biohydrogel (Bio-PEC hydrogel) made from a precursor dough, by kneading, annealing, and crosslinking the dough of two oppositely charged polysaccharides, cationic chitosan quaternary ammonium salt (HACC) and anionic sodium hyaluronate (HA), photoinitiator (α-ketoglutaric acid), crosslinker glycidyl methacrylate (GMA), and water of very small quantity is reported. Controlled kneading and annealing homogenized the dough with respect to transforming randomly distributed, individual polymer chains into tightly wound double-stranded structures, which, upon UV irradiation, covalently sparsely crosslinked into a highly entangled network and subsequently, upon fully swollen in water, results in Bio-PEC hydrogel, HACC/HA, exhibiting near-perfect elasticity, high tensile strength, and high swelling resistance. Via the same kneading and annealing, tetracarboxyphenylporphyrin iron (Fe-TCPP) metal nanoclusters are incorporated into HACC/HA to obtain photocatalytic, antibacterial, and biocompatible Bio-PEC hydrogel composite, Fe-TCPP@HACC/HA. Using SD rat models, the efficacy of Fe-TCPP@HACC/HA in inhibiting Escherichia coli (E. coli) growth in vitro and the ability to promote wound healing and scar-free skin regeneration in vivo, or its high potential as a wound dressing material for biomedical applications are demonstrated.