Efficacy and safety of combined anlotinib-oral etoposide treatment for patients with platinum-resistant ovarian cancer.

OBJECTIVE: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. METHODS: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. RESULTS: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1-68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9-100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3-11.6). The incidence of adverse events (any grade) was 100%, and the incidence of grade 3-4 adverse events was 54.5%. CONCLUSION: Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Preparation and Characterization of Aronia melanocarpa/Gellan Gum/Pea Protein/Chitosan Bilayer Films.

In this study, pH-sensitive bilayer hydrogel films with different AM contents (0.00%, 0.50%, 1.00%, 1.50%, 2.00% and 2.50%) were constructed. The films took AM/GG hydrogel as the inner layer structure and a pea protein (PP)/chitosan (CS) composite system as the outer structure. Film formation and the effect of AM were clarified through the detection and analysis of mechanical properties, microstructure, pH sensitivity and fresh-keeping ability. Results showed that AM exhibited good compatibility with each substance in the composite film, which were evenly dispersed in the system. The addition of AM significantly improved the water content, tensile strength, elongation at break, puncture resistance, oil resistance and water resistance of the composite films. The antioxidant activity, pH sensitivity and fresh-keeping effect of the composite film on fresh pork were remarkably enhanced. Moreover, it was found that the composite film containing AM effectively inhibited the production of total volatile base nitrogen (TVN) in fresh pork and significantly reduced the weight loss of fresh pork due to water loss during storage. Therefore, the functional properties revealed that AM was more positive to the comprehensive performance of films, and the AM-GG/PP-CS bilayer film containing AM exhibited strong potential for use in food preservation and packaging as a food freshness indicator to test food quality changes in storage.

Inhibition of persimmon tannin extract on guinea pig skin pigmentation.

BACKGROUND: In daily life, excessive exposure to ultraviolet light can lead to pigmentation. AIMS: This study is to determine the mechanism of persimmon tannin extract in inhibiting pigmentation, to investigate whether the effect of persimmon tannin extract is superior to that of arbutin, and to detect the optimal concentration. METHODS: In this study, the guinea pig pigmentation model was established by ultraviolet B (UVB) irradiation. With arbutin as a positive control, Masson-Fontana silver staining was used to observe the effects of persimmon tannin extract on melanin distribution in guinea pigs' skin tissue. Then, the tyrosinase activity was measured, and an Enzyme-linked immunosorbent assay was used to investigate the contents of antioxidant enzymes, inflammatory factors, and signaling pathway inhibitors in guinea pigs' skin tissue. RESULTS: The results showed that compared with the model group, superoxide dismutase, catalase, glutathione peroxidase, DKK1 content of Wnt/-catenin signaling pathway inhibitors levels, and inhibitory tyrosinase activity were increased by 24.3%, 33.3%, 59.3%, 36.81%, and 17.16%, respectively. Meanwhile, the interleukin-6 and interleukin-8 expression were reduced by approximately 22.2% and 54%. The results also showed that persimmon tannin extract could significantly reduce melanin density. The differences in experimental results were statistically significant (P < .01). CONCLUSIONS: Compared with the arbutin group, the medium-dose group (persimmon tannin extract of 20%) had a more significant effect on inhibiting pigmentation. Persimmon tannin could serve as a promising agent for preventing skin pigmentation. It is expected to provide ideas for the development of deep-processed persimmon products related to functional foods and cosmetics.

Sirtuin 1 promotes autophagy and proliferation of endometrial cancer cells by reducing acetylation level of LC3.

Endometrial cancer (EC) constitutes a common female genital tract tumor with a rising incidence rate. Sirtuin 1 (SIRT1) is a member of histone deacetylase, which extensively participates in the progression of aging, cell death, and tumorigenesis. This study explored the effect of SIRT1-mediated LC3 acetylation on autophagy and proliferation of EC cells. SIRT1 expression in EC tissues and adjacent tissues, EC cell lines and normal human epithelial cells was detected. SIRT1 expression was elevated in EC cell lines and tissues. Knockdown of SIRT1 inhibited proliferation, migration, and invasion of EC cells. Then, EC cells were starved in serum-free medium, and levels of autophagy-related proteins were detected. Starvation induced autophagy of EC cells. The starvation-treated EC cells showed an increased SIRT1 expression, a decreased LC3 acetylation level and an increased autophagy level. The proliferation and autophagy of EC cells under different treatments were evaluated. In EC cells transfected with overexpressing SIRT1, LC3 acetylation was inhibited and cell proliferation was promoted. Moreover, overexpressing SIRT1 facilitated growth and autophagy of transplanted tumors in nude mice. In conclusion, SIRT1 promoted autophagy and proliferation of EC cells by reducing acetylation level of LC3.

Synthesis, crystal structures and insulin-like activity of three new oxidovanadium(V) complexes with aroylhydrazone ligand.

Three new oxidovanadium(V) complexes were designed, synthesized and characterized by C, H, N elemental analysis, single crystal X-ray diffraction，UV/Vis and IR spectra. Complex 1: [VOL1X] (H2L1 = (E)-N'-(2-hydroxybenzylidene)-3-methbenzohydrazide, HX = ethylmaltol = 2-ethyl-3-hydroxy-4-pyrone), Complex 2: [VOL2(CH3O)(CH3OH)], (H2L2 = C16H16N2O4 = (E)-N'-(2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide, CH3OH = methanol), Complex 3: [VOL3X] (H2L3 = (E)-N'-(3-ethoxy-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide). The insulin-like activity of the three complexes was tested. Both normal and streptozotocin (STZ)-diabetic mice were administered intragastrically for two weeks. It was found that the complexes at doses of 10.0 and 5.0 mg V·kg-1 can significantly decrease the blood glucose level in STZ-diabetic mice, and the blood glucose level in the treated normal mice was not altered. The lesions of kidney and liver caused by diabetes have varying degrees of improvement.

Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents.

1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti-inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic.

Synthesis, structures and Helicobacter pylori urease inhibitory activity of copper(II) complexes with tridentate aroylhydrazone ligands.

A series of new copper(II) complexes were prepared. They are [CuL(1)(NCS)] (1), [CuClL(1)]·CH3OH (2), [CuClL(2)]·CH3OH (3), [CuL(3)(NCS)]·CH3OH (4), [CuL(4)(NCS)]·0.4H2O (5), and [CuL(5)(bipy)] (6), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, 4-bromo-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide and 2-chloro-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, respectively, L(5) is the dianionic form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra and single crystal X-ray diffraction. The Cu atoms in complexes 1, 2, 3, 4 and 5 are coordinated by the NOO donor set of the aroylhydrazone ligands, and one Cl or thiocyanate N atom, forming square planar coordination. The Cu atom in complex 6 is in a square pyramidal coordination, with the NOO donor set of L(1), and one N atom of bipy defining the basal plane, and with the other N atom of bipy occupying the apical position. Complexes 1, 2, 3, 4 and 5 show effective urease inhibitory activities, with IC50 values of 5.14, 0.20, 4.06, 5.52 and 0.26µM, respectively. Complex 6 has very weak activity against urease, with IC50 value over 100µM. Molecular docking study of the complexes with the Helicobacter pylori urease was performed. The relationship between structures and urease inhibitory activities indicated that copper complexes with square planar coordination are better models for urease inhibition.

Synthesis, structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases.

A series of new cobalt(III) complexes were prepared. They are [CoL(1)(py)3]·NO3 (1), [CoL(2)(bipy)(N3)]·CH3OH (2), [CoL(3)(HL(3))(N3)]·NO3 (3), and [CoL(4)(MeOH)(N3)] (4), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N'-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N'-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC50 values of 4.27 and 0.35 µmol L(-1), respectively. Complex 2 has medium activity against urease, with IC50 value of 68.7 µmol L(-1). While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed.

Synthesis, Crystal Structures and Urease Inhibition of N'-(2-Bromobenzylidene)-2-(4-nitrophenoxy) acetohydrazide and N'-(4-Nitrobenzylidene) -2-(4-nitrophenoxy)acetohydrazide.

Two new hydrazone compounds, N'-(2-bromobenzylidene)-2-(4-nitrophenoxy)acetohydrazide (1) and N'-(4-nitrobenzylidene)-2-(4-nitrophenoxy)acetohydrazide (2), were prepared and structurally characterized by elemental analysis, IR, UV-Vis and (1)H NMR spectroscopy, and single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic space group P2(1)/n with unit cell dimensions of a = 5.3064(5) Å, b = 18.202(2) Å, c = 15.970(2) Å, ß = 95.866(3)º, V = 1534.4(2) Å(3), Z = 4, R(1) = 0.0457, and wR(2) = 0.0975. Compound 2 crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions of a = 4.6008(7) Å, b = 14.451(2) Å, c = 23.296(3) Å, ß = 93.620(2)º, V = 1545.8(4) Å(3), Z = 4, R(1) = 0.0441, and wR2 = 0.0985. Structures of the compounds are stabilized by hydrogen bonds and π···π interactions. The urease inhibitory activities of the compounds were studied. Both compounds show strong urease inhibitory activities, with IC(50) values of 8.4 and 20.2 µM, respectively.

Aromatic diacylhydrazine derivatives as a new class of polo-like kinase 1 (PLK1) inhibitors.

A novel class of aromatic diacylhydrazine derivatives was designed as PLK1 inhibitors. All the 19 new synthesized compounds were assayed for antitumor activity against the respective cervical cancer cells. In which, nine compounds with better antitumor activities were further tested for their PLK1 inhibitory activity. Last, we have successfully found that compound 7k showed both the promising antitumor activity with IC50 of 0.17 µM against the cervical cancer cells, and also processed the most potent PLK1 inhibitory activity with IC50 of 0.03 µM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and PKL1 (PDB code: 1umw) protein.

Pyrolytic and kinetic characteristics of the thermal decomposition of Perilla frutescens polysaccharide.

The thermal decomposition of Perilla frutescens polysaccharide was examined by thermogravimetry, differential thermogravimetry, and differential thermal analysis. The results showed that the mass loss of the substance proceeded in three steps. The first stage can be attributed to the expulsion of the water from ambient temperature to 182°C. The second stage corresponded to devolatilization from 182°C to 439°C. The residue slowly degraded in the third stage. The weight loss in air is faster than that in nitrogen, because the oxygen in air accelerated the pyrolytic reaction speed reaction. The heating rate significantly affected the pyrolysis of the sample. Similar activation energies of the degradation process (210-211 kJ mol⁻¹) were obtained by the FWO, KAS, and Popescu techniques. According to Popescu mechanism functions, the possible kinetic model was estimated to be Avrami-Erofeev 20 g(α) = [-ln(1-α)]4.