Can the Pathological Response in Patients with Locally Advanced Gastric Cancer Receiving Neoadjuvant Treatment Be Predicted by the CEA/Albumin and CRP/Albumin Ratios?

Background: The purposes of neoadjuvant chemotherapy are to tumor size to improve the tumor removal rate, extend survival, and prevent metastasis. In this study, the importance of CRP/albumin ratio and CEA/albumin ratio in the prediction of neoadjuvant treatment response in gastric cancer patients was evaluated. Methods: This study retrospectively included 135 gastric cancer patients who received neoadjuvant chemotherapy at Çukurova University Balcali Hospital between January 2018 and December 2023. Preoperative CRP/albumin and CEA/albumin ratios were compared according to treatment response and multivariate logistic regression analysis was performed to determine the potential importance of these ratios in predicting pathological response. Results: The mean age of the 135 patients was 58.79 ± 10.83 (min = 26-max = 78). The CRP/albumin and CEA/albumin ratios were found to be significantly lower in patients who did not respond to neoadjuvant therapy. Each 1-unit increase in the CRP/albumin ratio was associated with a 1.16-fold decrease in the odds of pathological complete response to neoadjuvant therapy. Both CRP/albumin and CEA/albumin ratios were found to be significant in distinguishing neoadjuvant therapy response. The optimal cut-off value was 2.74 for the CRP/albumin ratio (sensitivity = 60%, specificity = 78.4%) and 1.40 for the CEA/albumin ratio (sensitivity = 74.2%, specificity = 67.6%). Values below these cut-off points favored neoadjuvant therapy response. Pathological complete response to neoadjuvant therapy was 4.75 times higher in patients with a CRP/albumin ratio below 2.74 and 5.14 times higher in patients with a CEA/albumin ratio below 1.40. Conclusions: Findings demonstrate that in patients with locally advanced gastric cancer receiving neoadjuvant treatment, CRP/Albumin and CEA/Albumin ratios are significant markers of pathological response.

Synthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties.

The main objective of the present study was to synthesize potential inhibitor/activators of AChE and hCA I-II enzymes, which are thought to be directly related to Alzheimer's disease. Dithiodibenzothioate compounds were synthesized by thioesterification. Six different thiolate compounds produced were characterized by 1H-, 13C-NMR, FT-IR, LC-MS/MS methods. HOMO-LUMO calculations and electronic properties of all synthesized compounds were comprehensively illuminated with a semi-empirical molecular orbital (SEMO) package for organic and inorganic systems using Austin Model 1 (AM1)-Hamiltonian as implemented in the VAMP module of Materials Studio. In addition, the inhibition effects of these compounds for AChE and hCA I-II in vitro conditions were investigated. It was revealed that TE-1, TE-2, TE-3, TE-4, TE-5, and TE-6 compounds inhibited the AChE under in vitro conditions. TE-1 compound activated the enzyme hCA I while TE-2, TE-3 TE-4 compounds inhibited it. TE-5 and TE-6, on the other hand, did not exhibit a regular inhibition profile. Similarly, TE-1 activated the hCA II enzyme whereas TE-2, TE-3, TE-4, and TE-5 compounds inhibited it. TE-6 compound did not have a consistent inhibition profile for hCA II. Docking studies were performed with the compounds against AChE and hCA I-II receptors using induced-fit docking method. Molecular Dynamics (MD) simulations for best effective three protein-ligand couple were conducted to explore the binding affinity of the considered compounds in semi-real in-silico conditions. Along with the MD results, TE-1-based protein complexes were found more stable than TE-5. Based on these studies, TE-1 compound could be considered as a potential drug candidate for AD.Communicated by Ramaswamy H. Sarma.

Investigation of in vitro and in silico effects of some novel carbazole Schiff bases on human carbonic anhydrase isoforms I and II.

Carbonic anhydrases (CAs, EC4.2.1.1) are metalloenzymes that catalyse reversible hydration reaction of carbon dioxide to bicarbonate and protons. In recent years, there has been a great interest in inhibitors/activators of carbonic anhydrase isoenzymes. Therefore, we investigated the effects of four different carbazole Schiff base derivatives, which are believed to have a potential to be used as a drug, on human carbonic anhydrase (hCA) isoenzymes I and II under in vitro conditions. The IC50 values of carbazole Schiff base derivatives were found to be in the range of 32.09-151.2 µM for hCA isoenzyme I and 21.82-40.54 µM for hCA isoenzyme II. Among all compounds, (E)-3-(((9-Octyl-9H-carbazole-3-yl)imino)methyl)benzene-1,2-diol (C3) had the strongest inhibitory effect on hCA isoenzyme II. It was determined that 2,3,4-trimethoxy and 4-hydroxy phenyl containing carbazole compounds have selective inhibition against hCA II isoenzyme. Docking studies were performed against hCA I and II receptors using induced-fit docking method. The compounds had affinity scores varying from -7.74 ± 0.27 to -6.27 ± 0.07 kcal/mol for hCA I and from -8.04 ± 0.17 to -7.27 ± 0.18 kcal/mol for hCA II.Communicated by Ramaswamy H. Sarma.

Antibacterial and antioxidant activities of traditional medicinal plants from the Erzurum region of Turkey.

BACKGROUND: In this study, 13 different extracts were investigated which are grown in the region of Erzurum. OBJECTIVE: The aim of this study was to screen various plant extracts that are known and used for medicinal purposes such as Ferula communis L., Rumex patientia L., Gundelia tournefortii L., Rheum ribes L., Asphodeline taurica, Polygonum arenastrum, Allium schoenoprasum L., and Ferula orientalis L. MATERIALS AND METHODS: Medicinal parts of plants such as leaves, flowers, and stems were investigated by 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and cupric reducing antioxidant capacity assays: Centaury and Blackthorn. Total phenolic content, total flavonoid content, and antimicrobial properties were also determined. Antibacterial and antifungal activities were investigated by the microdilution method and the agar diffusion method respectively. RESULTS: Accordingly, the results of the Rheum ribes L. plant have the highest antioxidant activity among all analyses made. But in almost all antioxidant analysis methods, the lowest antioxidant activity was found in Ferula orientalis L. According to the antibacterial analysis applied, it was found that the plant extracts were generally more effective on yeast strains than the test bacteria used; that is, most of the plants have antifungal effect. CONCLUSIONS: Due to their antimicrobial, antifungal, and antioxidant properties, the extracts of these plants might be used as natural sources in the pharmaceutical and cosmetic industries.

The determination of the carbonic anhydrases activators in vitro effect of mixed donor crown ethers.

Carbonic anhydrases (CAs) play an important function in various physiological and pathological processes. Therefore, many researchers work in this field in order to design and synthesize new drugs. Both inhibitors and activators of CAs, which are associated with the diagnosis and treatment of many diseases, are very important. The emergence of the use of CA activators in the treatment of Alzheimer has led many scholars to work on this issue. In this study, CA activators and inhibitors are determined. The crown ethers compounds (1, 2, 3, 6, 7, 8, and 9) were found to cause activation on enzyme activities of hCA I and II. The AC50 values on hCA I and II of the compounds are in the range of 4.6565-374.979 µM. The 4 (IC50 ; 1.301 and 3.215 µM for hCA I and II) and 5 (IC50 ; 73.96 and 378.5 µM for hCA I and II) compounds were found to cause inhibition on enzyme activities of hCA I and II.

Secondary Sulfonamides as Effective Lactoperoxidase Inhibitors.

Secondary sulfonamides (4a-8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a-8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a-8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a-8h) were found in the range of 1.096 × 10-3 to 1203.83 µM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxybenzamide (6a), with Ki values of 1.096 × 10-3 ± 0.471 × 10-3 µM as non-competitive inhibition.

Purification and characterization of dihydropyrimidine dehydrogenase enzyme from sheep liver and determination of the effects of some anaesthetic and antidepressant drugs on the enzyme activity.

Dihydropyrimidine dehydrogenase (DPD, E.C. 1.3.1.2) was purified from sheep liver with a yield of 16.7%, purification fold of 407.5 and specific activity of 0.705 EU/mg proteins. The purification procedure consisted of ammonium sulphate fractionation, DEAE ion exchange chromatography and 2',5'-ADP Sepharose-4B affinity chromatography. The molecular weight determined by SDS-PAGE and was found 111 kDa. Optimum pH, ionic strength temperature and stable pH were determined as 8.0, 0.9 mM, 50 °C and 6.0, respectively. The kinetic parameters (Km and Vmax) of the enzyme were determined with NADPH as 22.97 µM and 0.17 EU/mL, respectively. The same parameters were determined with uracil as 17.46 µM and 0.14 EU/mL, respectively. Additionally, in vitro inhibitory effects of some antidepressant drugs including escitalopram, fluoxetine, mirtazapine, haloperidol and some anaesthetic drugs including propofol and lidocaine were investigated against DPD. In addition, IC50 values for each active drug obtained for escitalopram, fluoxetine, mirtazapine, haloperidol, propofol and lidocaine were determined as 1736.11, 13.24, 86.65, 99.03, 0.21 and 15.07 µM, respectively.