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In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.
Subject(s)
Cholinesterase Inhibitors , Glycoside Hydrolase Inhibitors , Acetylcholinesterase/metabolism , alpha-Glucosidases/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Hypoglycemic Agents/pharmacology , Molecular Docking Simulation , Pyrans/pharmacology , Pyrans/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemistry , Structure-Activity Relationship , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacologyABSTRACT
A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1ß and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure-activity relationships of 8b, 8d, and 8e toward NO synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Naphthoquinones , Animals , Mice , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Lipopolysaccharides/pharmacology , Molecular Docking Simulation , Naphthoquinones/chemical synthesis , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II , RAW 264.7 Cells , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Macrophages/drug effectsABSTRACT
Oncology inpatients are at high risk of malnutrition. Identification of at risk patients by nutrition screening requires a practical and easy to use tool. The aim of this study was to determine the validity of the Bach Mai Boston Tool (BBT) compared to a 'gold standard' full nutrition assessment using the Patient-Generated Subjective Global Assessment (PG-SGA). A cross-sectional study was conducted on 270 oncology inpatients from January to December 2016. Cohen's Kappa, sensitivity, specificity and ROC analyses were performed. 270 inpatients were included in this study with a mean age of 56.3 ± 12.1 years old. Of these patients, 51.8% were male, and 74.1% had gastrointestinal cancer. The mean body mass index of patients was 20.6 ± 3.0 kg/m2. The PG-SGA tool identified 146 (54.1%) malnourished patients, while the BBT identified 105 (39.9%) malnourished patients. The BBT had a medium consistency, with a Kappa value of 0.6. Using a cut-off point of ≥ 4, the BBT had a sensitivity of 87.7% and a specificity of 72.6%. On the other hand, a BBT with a cut-off point ≥ 5 resulted in a sensitivity of 67.1%, a specificity of 94.4%, and an AUC of 0.81. The BBT is a practical, informative and valid tool for detecting malnutrition in hospitalized oncology patients. We recommend using a cut-off point of 4 for screening the risk of malnutrition for oncology inpatients.
Subject(s)
Early Detection of Cancer/methods , Inpatients/statistics & numerical data , Medical Oncology/methods , Neoplasms/diagnosis , Nutrition Assessment , Aged , Cross-Sectional Studies , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Humans , Male , Malnutrition/diagnosis , Malnutrition/therapy , Middle Aged , Neoplasms/therapy , Nutritional Status , ROC CurveABSTRACT
Sulfur compounds in fuel such as thiophene, benzothiophene and dibenzothiophene are the primary source of SO x emissions, leading to environmental pollution and acid rain. In this study, we synthesized a layered oxygen-doped graphitic carbon nitride (OCN) structure and integrated ZnO and TiO2 nanoparticles onto the OCN surface through a microwave-assisted sol-gel method. The X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) results confirmed a robust interaction between the ZnO and TiO2 nanoparticles and the oxygen-doped g-C3N4 (OCN) surface, as indicated by the formation of C-N-Ti and C-O-Ti bonds. This interaction notably improved the optoelectronic properties of the ZnO-TiO2/OCN composite, yielding increased visible light absorption, reduced charge recombination rate, and enhanced separation and transfer of photogenerated electron-hole pairs. The oxygen doping into the CN network could alter the band structure and expand the absorption range of visible light. The ZnO-TiO2/OCN photocatalyst demonstrated remarkable desulfurization capabilities, converting 99.19% of dibenzothiophene (DBT) to dibenzothiophene sulfone (DBT-O2) at 25 °C, and eliminating 92.13% of DBT from real-world fuel oil samples. We conducted in-depth analysis of the factors impacting the redox process of DBT, including the ZnO ratio, initial DBT concentration, catalyst dosage, stability, and O/S molar ratio. Radical trapping experiments established that ËO2 -, ËOH and h+ radicals significantly influence the reaction rate. The obtained results indicated that the ZnO-TiO2/OCN photocatalyst represents a promising tool for future fuel oil desulfurization applications.
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BACKGROUND: This study aimed to evaluate the effectiveness of modified Billroth-II with a hinged anti-peristaltic afferent loop by comparing it with the Roux-en-Y method. METHODS: We retrospectively analyzed 344 patients with gastric cancer who underwent distal gastrectomy between 2016 and 2021. Propensity score matching was conducted to balance baseline characteristics. RESULTS: After propensity score matching, there were 117 patients in each group. The Billroth-II group was significantly better regarding operating time (184.7 vs 225.3 minutes), postoperative hospital stays (7.9 vs 9.2 days), and time to semi-solid diet tolerance (2.8 vs 3.8 days). The Billroth-II group demonstrated comparable results with the Roux-en-Y group in weight loss, hemoglobin changes, reflux esophagitis, food residue, and gastritis severity. Presentation of bile in gastric remnant was significantly higher in the Billroth-II group (42.9% vs 10.3%). CONCLUSION: There were no significant differences in functional outcomes between Billroth-II and Roux-en-Y reconstructions. The Billroth-II was superior to Roux-en-Y in operating time, hospital stays, and time to semi-solid diet tolerance. The Billroth-II could be considered an acceptable alternative reconstruction after distal gastrectomy.
Subject(s)
Anastomosis, Roux-en-Y , Gastrectomy , Gastroenterostomy , Propensity Score , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Gastrectomy/methods , Gastrectomy/adverse effects , Male , Female , Middle Aged , Retrospective Studies , Gastroenterostomy/methods , Anastomosis, Roux-en-Y/methods , Aged , Treatment Outcome , Length of Stay/statistics & numerical data , Operative Time , Postoperative Complications/etiology , Postoperative Complications/epidemiologyABSTRACT
PURPOSE: In recent years, laparoscopic near-total gastrectomy (LnTG) has emerged as a surgical option for gastric cancer in the middle-third of the stomach. However, its application in locally advanced stages presents technical challenges. This study aims to provide a detailed analysis of the operative outcomes and long-term functional and oncological results of totally LnTG in combination with D2 lymphadenectomy for middle-third gastric cancer. PATIENTS AND METHOD: A prospective study was conducted on 79 patients who underwent totally LnTG and D2 lymphadenectomy for middle-third gastric cancer between January 2017 and December 2021. Short-term outcomes included operative characteristics, and the evaluation of gastroesophageal reflux and gastric remnant condition using endoscopy based on the Los Angeles (LA) and Residue-Gastritis-Bile classifications. Long-term oncological outcomes included overall survival and disease-free survival. RESULTS: Totally LnTG was successfully performed in 98.7% of patients without intraoperative complications or conversions to laparotomy. The mean operation time was 202.2±43.0 min, and the median blood loss was 50 (50;100) mL. The overall incidence of postoperative morbidities was 16.5%, with one patient experiencing a narrowing of the gastrojejunostomy, successfully treated by endoscopic balloon dilation. All patients had tumor-free resection margins, and there were no mortalities. The 5-year overall survival and disease-free survival rates were 80% and 55%, respectively. CONCLUSIONS: Totally LnTG is an effective and feasible approach for gastric cancer in the middle-third of the stomach, yielding favorable short-term outcomes and acceptable long-term results. Routine application of totally LnTG for middle-third gastric cancer is practical and promising.
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Introduction Lymph node (LN) metastasis happens even in early gastric cancer (GC) even in LN stations that are not adjacent to the primary tumor. Total or subtotal gastrectomy (TG or sTG) can be performed in the middle third of the GC if the negative proximal margin is maintained. These procedures differed in the extent of LN dissection; therefore, oncology considerations must be taken into consideration when selecting the appropriate procedure. Methods This was a cross-sectional study involving 98 patients suffering from middle-third GC. The metastatic lymph nodes (mLN) ratio was calculated in each case by the ratio between the number of mLN and the number of total LNs retrieved. We compare the difference in the total LN retrieved, number of mLN, and rate of positive LN (N+) between the two groups TG and sTG. Results The majority of patients had advanced GC (82.7% pT2-4). About 65.3% of patients had metastasis LN. The events of LN metastasis and skipped LN metastasis happened even in tumors contained in the submucosal layer. The metastasis rates in each LN station were also increasing in correlation with the depth of tumor invasion. For LN station No. 2, 4sa, 10, 11d (which are not mandatory) in sTG, the rate of mLN was 0% for the pT1-3 tumor, regardless of tumor longitudinal location. The rate of mLN for each station was higher in adjacent stations of the tumor (No. 1-3-5-7 in lesser curvature, No. 4sb-4d-6 in greater curvature, No.1-3-4sb in the anterior wall, No. 3-7-12a in the posterior wall). The total LN retrieved, number of mLN, and rate of positive LN were statistically higher in the TG group compared to the sTG group. However, the mean mLN ratios between the two groups were comparable (p = 0.116). Conclusion In accordance with the macroscopic and microscopic characteristics, we observed a stratified distribution of mLN in the middle third of the GC. With these early results, sTG combined with standard lymphadenectomy was an acceptable treatment for T1-T3 middle-third GC in terms of mLN distribution. Total No. 4sb LN dissection might also be reserved in gastrectomy for T1-T3 GC.
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BACKGROUND: Incisional hernia (IH) can be treated with an intraperitoneal on-lay mesh (IPOM). This study aimed to evaluate the surgical outcomes, recurrence rates, and chronic pain after laparoscopic IH repair. METHOD: The data of 50 patients who underwent laparoscopic IPOM repair between March 2018 and May 2021 were prospectively collected. RESULTS: The standard IPOM technique was used on 41 patients (82%), whereas the IPOM-plus technique was used on nine patients (18%). There was a history of IH repair for 12 patients (24%), and two of them recurrent hernias. The average body mass index was 24.7, and the average defect size was 17.6 cm2 . The mean operative time was 145.7 minutes, and the mean hospital stay was 3.5 days. There were minor complications in nine patients (18%), a case of bowel injury (2%), and a case of bladder injury (2%). Recurrent hernias were observed in three patients (6%) over a mean follow-up period of 17.9 months (4-36 months). One patient had postoperative chronic pain lasting 3 months. The width and size of the hernia were risk factors for recurrence. CONCLUSION: Laparoscopic IPOM repair was a safe and effective method of treating IH, with a low incidence of postoperative complications, chronic pain, and recurrence.
Subject(s)
Chronic Pain , Hernia, Ventral , Incisional Hernia , Laparoscopy , Chronic Pain/etiology , Hernia, Ventral/etiology , Hernia, Ventral/surgery , Herniorrhaphy/methods , Humans , Incisional Hernia/etiology , Incisional Hernia/surgery , Laparoscopy/methods , Pain, Postoperative/etiology , Pain, Postoperative/surgery , Prospective Studies , Recurrence , Surgical MeshABSTRACT
A series of schiartane C29 nortriterpenoids with 5/5/7/6/5 membered consecutive rings (1â5) with an unique schinortriterpenoid skeleton including a new, kadcoccilactone V (1), together with four known ones (2â5) and three known triterpenoids (6â8) were identified from stems of Kadsura coccinea (Lem.) A. C. Smith. The structures of 1 and known compounds were elucidated by interpretation of 1D and 2D NMR, and HR-ESI-MS data as well as comparing those data in the literature. All the isolated compounds were examined for cytotoxic effects against six human cancer cell lines [(HCT-15 (colon), NUGC-3 (stomach), NCI-H23 (lung), ACHN (renal), PC-3 (prostate), and MDA-MB-231 (breast)]. Among them, compound 6 showed potent cytotoxicity against NCI-H23 (GI50 1.28 µM) and NUGC-3 (GI50 1.28 µM), and significantly inhibited on PC-3, MDA-MB-231, ACHN, HCT-15 with GI50 values around 2.33 to 2.67 µM.
Subject(s)
Kadsura , Triterpenes , Cell Line , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Stems , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
This paper mainly deals with the isovaleraldehyde degradation with the help of a nonthermal plasma surface discharge (NPSD) coupled with photocatalysis. The efficiency of NPSD reactor, for gas treatment, was studied for different binary mixtures: (1) mixture of aldehydes (Isovaleraldehyde and Butyraldehyde) and (2) mixture of aldehyde and amine (Isovaleraldehyde and Trimethylamine). A planar continuous reactor is used to investigate the effect of addition of another pollutant on the performance of oxidation process. A synergetic effect was observed by combining NPSD and photocatalysis for the degradation of mixture of pollutants. In addition, combined NPSD/photocatalysis has significantly enhanced the CO2 selectivity, as compared to NPSD alone. This is attributed to the formation of more reactive species due to the presence of TiO2 in the plasma discharge zone. Moreover, ozone and UV light on TiO2, produced by plasma, have activated the surface leading to enhanced mineralization. In addition, the byproducts of each binary mixture were identified and evaluated.
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Multidrug resistance in the nosocomial pathogen Acinetobacter baumannii limits therapeutic options and impacts on clinical care. Resistance against carbapenems, a group of last-resort antimicrobials for treating multidrug-resistant (MDR) A. baumannii infections, is associated with the expression (and over-expression) of carbapenemases encoded by the blaOXA genes. The aim of this study was to determine the prevalence of antimicrobial-resistant A. baumannii associated with infection in three hospitals in southern Vietnam and to characterize the genetic determinants associated with resistance against carbapenems. We recovered a total of 160 A. baumannii isolates from clinical samples collected in three hospitals in southern Vietnam from 2012 to 2014. Antimicrobial resistance was common; 119/160 (74 %) of isolates were both MDR and extensively drug resistant (XDR). High-level imipenem resistance (>32 µg ml-1) was determined for 109/117 (91.6 %) of the XDR imipenem-nonsusceptible organisms, of which the majority (86.7 %) harboured the blaOXA-51 and blaOXA-23 genes associated with an ISAba1 element. Multiple-locus variable number tandem repeat analysis segregated the 160 A. baumannii into 107 different multiple-locus variable number tandem repeat analysis types, which described five major clusters. The biggest cluster was a clonal complex composed mainly of imipenem-resistant organisms that were isolated from all three of the study hospitals. Our study indicates a very high prevalence of MDR/XDR A. baumannii causing clinically significant infections in hospitals in southern Vietnam. These organisms commonly harboured the blaOXA-23 gene with ISAba1 and were carbapenem resistant; this resistance phenotype may explain their continued selection and ongoing transmission within the Vietnamese healthcare system.