[Predictors of postoperative remission of acromegaly. (Experience of the Burdenko Neurosurgical Center)]. / Prediktory posleoperatsionnoi remissii akromegalii. (Opyt FGAU «NMITs neirokhirurgii im. akad. N.N. Burdenko¼).

BACKGROUND: Treatment of acromegaly is still an unresolved problem. Overall postoperative remission rate ranges from 34 to 85%. These values are better for microadenomas (75-90%) and worse for macroadenomas (45-70%). Identification of predictors of acromegaly remission after surgical treatment is an urgent objective to improve the quality of medical care for these patients. OBJECTIVE: To analyze postoperative freedom from acromegaly and predictors of remission. MATERIAL AND METHODS: A retrospective single-center study included 227 patients with acromegaly who underwent resection of pituitary adenoma between August 2018 and August 2021. RESULTS: Remission (normalization of serum IGF-1) was achieved in 65 (55%) patients. Growth hormone and IGF-1 index decreased after surgery in all patients. Mean preoperative serum growth hormone was 12.45 [6.88, 29.85] ng/ml, early postoperative concentration - 1.54 [0.80, 3.38] ng/ml, in delayed period - 1.15 [0.57, 3.80] ng/ml. Mean IGF-1 index was 2.18 [1.69, 2.71], 1.47 [0.99, 1.90] and 0.99 [0.74, 1.43], respectively. CONCLUSION: Significant predictors of acromegaly remission after neurosurgical treatment were age, preoperative level of growth hormone, tumor size and location, growth hormone and IGF-1 index in early postoperative period and residual tumor after surgery. Multivariate analysis revealed a significant association of acromegaly remission with small tumor size, low postoperative level of growth hormone and no residual tumor within 3-6 month after surgery.

Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation.

Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).

The preventive effects of Ulva lactuca aqueous extract, ulvan polysaccharides and atorvastatin on ethylene glycol-induced hyperoxaluria.

OBJECTIVE: Kidney stones are a common complication of hyperoxaluria. The aim of this study is to investigate the protective and preventive effects of Ulva lactuca aqueous extract, ulvan polysaccharides and atorvastatin on ethylene glycol-induced hyperoxaluria. MATERIALS AND METHODS: Male Wistar rats between 110 and 145 g in weight were used in the study, Ulva lactuca aqueous extract and polysaccharides were prepared. The male albino rats were supplemented with 0.75 percent ethylene glycol (v/v) in their drinking water for six weeks to induce hyperoxaluria. Ulvan infusions (100 mg/kg body weight), ulvan polysaccharides (100 mg/kg body weight), and atorvastatin (two milligrams/kg body weight) to treat hyperoxaluric rats for four weeks (every other day) were used. Weight loss, serum creatinine, serum urea, serum uric acid, serum oxalate, kidney oxalate, kidney lipid peroxidation, and kidney DNA fragmentation and kidney histopathological studies were done. RESULTS: Weight loss, rise of serum creatinine, serum urea, serum uric acid, serum oxalate, kidney oxalate, kidney lipid peroxidation, and kidney DNA fragmentation were all shown to be prevented by the addition of atorvastatin, polysaccharides, or aqueous extract, respectively. Catalase (CAT) activity, glutathione peroxidase (GPX) activity, glutathione-S-transferase (GST) activity, and histopathological perturbations were all significantly reduced by the medicines that were studied. CONCLUSIONS: Hyperoxaluria caused by ethylene glycol may be prevented by a combination of Ulva lactuca aqueous extract, ulvan polysaccharides, and atorvastatin. A reduction in renal oxidative stress and an improvement of the antioxidant defense system may be responsible for these protective benefits. However, Ulva lactuca infusion and ulvan polysaccharides need to be studied further in humans, in order to determine their efficacy and safety.

Exploring marine-derived compounds for MET signalling pathway inhibition in cancer: integrating virtual screening, ADME profiling and molecular dynamics investigations.

The MET signalling pathway regulates fundamental cellular processes such as growth, division, and survival. While essential for normal cell function, dysregulation of this pathway can contribute to cancer by triggering uncontrolled proliferation and metastasis. Targeting MET activity holds promise as an effective strategy for cancer therapy. Among potential sources of anti-cancer agents, marine organisms have gained attention. In this study, we screened 47,450 natural compounds derived from marine sources within the CMNPD database against the Met crystal structure. By employing HTVS, SP, and XP docking modes, we identified three compounds (CMNPD17595, CMNPD14026, and CMNPD19696) that outperformed a reference molecule in binding affinity to the Met structure. These compounds demonstrated desirable ADME properties. Molecular Dynamics (MD) simulations for 200 ns confirmed the stability of their interactions with Met. Our findings highlight CMNPD17595, CMNPD14026, and CMNPD19696 as potential inhibitors against Met-dependent cancers. Additionally, these compounds offer new avenues for drug development, leveraging their inhibitory effects on Met to combat carcinogenesis.

Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.

Ingenines A and B, Two New Alkaloids from the Indonesian Sponge Acanthostrongylophora ingens.

As a continuation of the work on EtOAc fraction of the Indonesian sponge Acanthostrongylophora ingens, 2 new alkaloids: one pyrimidine-ß-carboline alkaloid named ingenine A (2) and one pyrimidine-γ-carboline alkaloid named ingenine B (3), along with annomontine (1) were isolated. Their structures were unambiguously established on the basis of NMR spectroscopy ((1) H, (13)C, (1) H-(1) H COSY, HMQC, and HMBC) and mass spectral data. This is the first report of isolation pyrimidine-γ-carboline alkaloid from natural source. Compounds 1 and 3 showed pronounced cytotoxicity against the murine lymphoma L5178Y cancer cell line with ED50 7.8 and 9.1 µg/mL respectively, while compound 2 showed weak activity.

Stigmasterol Tetracosanoate, a New Stigmasterol Ester from the Egyptian Blepharis ciliaris.

A new stigmasterol ester: stigmasterol tetracosanoate (3), along with 7 compounds: ß-sitosterol (1), stigmasterol (2), (2S,3S,4R)-2[(2'R)-2'-(hydroxyeicosanoyl amino) octadecane-1,3,4-triol (4), apigenin (5), ß-sitosterol-3-O-ß-D-glucopyranoside (6), stigmasterol-3-O-ß-D-glucopyranose (7), and apigenin-7-O-ß-D-glucopyranoside (8) were isolated from Blepharis ciliaris aerial parts. Compounds 1, 2, and 5-7 are reported here for the first time from the plant and 4 for the first time from the family. GCMS analysis revealed the presence of 45 fatty acids, 53 hydrocarbons, and 24 sterols. The different fractions exhibited mild cytotoxic in brine shrimp assay and anti-hyperglycaemic activities. The EtOAc fraction and TME (total MeOH extract) showed weak anti-malarial activity against P. falciparum. The CHCl3 fraction gave potent -anti-inflammatory activity compared with indomethacin.

Proceraside A, a new cardiac glycoside from the root barks of Calotropis procera with in vitro anticancer effects.

We have studied the ethyl acetate fraction of the methanolic extract of the root barks of Calotropis procera (Asclepiadaceae) from Egypt. Bioassay-directed fractionation and final purification of the extract resulted in the identification of a new cardenolide glycoside named proceraside A (1) together with two known compounds, frugoside (2) and calotropin (3). Their structures were elucidated by extensive NMR studies and mass spectrometric data. The in vitro cytotoxicity of the isolated compounds was evaluated against A549 non-small cell lung cancer, U373 glioblastoma and PC-3 prostate cancer cell lines. They showed potent activity against the tested cancer cell lines with IC50 ranging from 0.005 to 0.3 µg/mL. Cisplatin was used as positive control.