Citrus wastewater as a source of value-added products: Quali-quantitative analysis and in vitro screening on breast cancer cell lines.

Citrus wastewater from industries is a source of bioactive compounds whose recovery could be a useful approach to convert processing waste into potential resources to be exploited in food, pharmaceutical, and chemical companies. Citrus wastewater, obtained from the industrial processing of Citrus sinensis, was freeze-dried and qualitative/quantitative evaluated using HPLC/MS Q-TOF analysis. Antiproliferative activity was investigated on MDA-MB-231 (triple-negative breast cancer cell line), MCF-7 (breast cancer cell line), and its multidrug-resistant variant MCF-7R. Fraction 8 emerged for its cytotoxicity toward MCF-7R cells. Its main component, the polymethoxylated flavone nobiletin (80%), is likely involved in increasing the number of G1-phase MCF-7R cells without inducing cell death. Notably, fraction 8 sensitizes MCF7-R cells to the antiproliferative effects of doxorubicin, thus contributing to overcoming MCF7-R multidrug resistance. Our studies highlighted the possibility of applying a sustainable strategy for citrus wastewater recycling to recover functional compounds as useful adjuvants for the prevention and treatment of malignancies.

Exploring novel NH-form resorcinol-based schiff base and its metal complexes: Synthesis, characterization, cytotoxic activity, molecular docking and ADME studies.

The research investigates the cytotoxic effects of the stable NH-form of a resorcinol-based Schiff base (HL) and its metal complexes (Zn(II), Cd(II), Cu(II), Ni(II)) on MCF-7 breast cancer cells. The structural characterization was conducted utilizing diverse analytical techniques, including mass spectrometry, elemental analysis, molar conductance, magnetic moment, UV-Vis, IR and ESR. The crystalline state analysis of HL through X-ray crystallography disclosed a hybrid structure comprising two canonical forms, specifically the quinoid and zwitterion, that contribute to resonance and diverse interactions, resulting in the development of a three-dimensional form. NMR, IR and ESR analyses showed that the HL was bidentate, using the oxygen of the hydroxyl and the nitrogen atom of azomethine, bonded to the metal center during complexation. The study explored the cytotoxic effects of HL and the various metal complexes on MCF-7 human breast cancer cells. All complexes display significant cytotoxicity (IC50 < 38.37 µM). The activity of the complexes was greater than that of the free ligand, with the Cu(II) complex followed by Zn(II) demonstrated superior cytotoxicity compared to Cd(II), and Ni(II) complexes. Notably, the Cu(II) and Zn(II) complex exhibited approximately 13.2 and 12.9 times greater cytotoxicity than the 5-F Uracil (5-FU) cancer drug. An MTT assay corroborated the antiproliferative activity. The molecular docking study has been performed for all compounds with the aromatase cytochrome P450 receptor protein associated with breast cancer (PDB code = 3eqm). ADME drug likeness model has been done.

Targeted isolation of lignans from the roots of Anthriscus sylvestris (L.) Hoffm. by small molecule accurate recognition technology.

Five undescribed lignans (1-5), along with sixteen known lignans (6-21), were isolated from the roots of Anthriscus sylvestris using small molecule accurate recognition technology (SMART). The structures of the isolated compounds were determined by comprehensive spectroscopic analyses, and the absolute configurations of compounds 3-5 were elucidated by comparison of their calculated and experimental ECD spectra. Compounds 5, 14-15, 19, and 21 exhibited significantly inhibitory effects against hypoxia-stimulated abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs). Moreover, compounds 5, 14-15, 19, and 21 can significantly restore expression of expression of PASMCs proliferation-related protein, including α-SMA, PCNA, P27, and CyclinD3, which are closely related to cell proliferation.

Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.

Key HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4+ T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.008). This decline persists for at least 12 weeks following cessation of the study drug. Sirolimus treatment also leads to a significant reduction in CD4+ T cell cycling and PD-1 expression on CD8+ lymphocytes. These data suggest that homeostatic proliferation of infected cells, an important mechanism for HIV persistence, is an intriguing therapeutic target.

Investigating the antioxidant and anticancer potential of Daucus spp. extracts against human prostate cancer cell line C4-2, and lung cancer cell line A549.

The study evaluated 297 carrot germplasm lines, focusing on 52 cultivars to explore their therapeutic potential and address challenges related to the accessibility and affordability of nutraceuticals. The investigation explores the application of DNA barcoding using the ITS region for precise species identification, highlighting genetic diversity among the examined cultivars. Through ITS sequence-based analysis and phylogenetic examination, six diverse Daucus spp. genotypes were differentiated and classified into distinct groups, indicating the presence of vast genetic variation. Evaluation of antioxidant activities using the DPPH radical scavenging assay revealed varying degrees of scavenging ability among genotypes with SKAU-C-15, SKAU-C-17, and SKAU-C-16 exhibiting the highest activity, suggesting their potential for antioxidant-rich products. Thin Layer Chromatography (TLC) bioautography confirmed the presence of bioactive compounds in carrot extracts responsible for their antioxidant properties. In cell culture studies, specific carrot genotype extracts demonstrated potential anti-proliferative and anti-metastatic effects on C4-2 (SKAU-C-30, SKAU-C-10, and SKAU-C-42) and A549 (SKAU-C-18 and SKAU-C-11) cancer cells, as indicated by MTT assay, wound healing assay, and Colony Forming Unit assay. These findings suggest the promising therapeutic potential of carrot genotypes for developing anti-cancer compounds or supplements. Overall, the study contributes to the nutrition and medical fields, paving the way for advancements in functional foods and health applications, particularly in cancer treatment or prevention.

Anticancer and anti-inflammatory effects of novel ethyl pyrazole derivatives having sulfonamide terminal moiety.

In the present work, a new series of ethyl pyrazole-containing compounds with side sulphonamide moiety was designed and synthesized. The new derivatives were divided into four groups based on the linker between the sulphonamide and pyridine ring attached to position 4 of the pyrazole ring and the substitution on the phenyl ring at position 3 of the same ring. The linker could be ethyl or propyl linkers. The phenyl ring is substituted with a methoxy group or hydroxyl group at position 3. The aim compounds were tested for their JNK1, JNK2, JNK3, and BRAF(V600E) activities. Compounds 23b, 23c, and 23d showed the highest activity with nanomolar IC50s. The most potent compound over JNK1 was 23d with an IC502 nM. While compound 23c was the most potent over JNK2 with an IC5057 nM. Finally, compound 23b was the most potent over JNK2 and BRAF(V600E) with IC50s of125 nM and 98 nM, respectively. After obtaining kinase inhibitory activity, the compounds were submitted to NCI to test their activity over different cell lines. Compound 23b showed the highest activity over most tested cell lines. In the second part of the present study, the final target compounds were tested for their anti-inflammatory effect. The anti-inflammatory effect of the new final compounds was performed by measuring their ability to inhibit inducible nitric oxide release and prostaglandin E2 production inhibition. Compound 23c showed the highest activity regarding nitric oxide release with IC50 0.63 µM, while compound 21d had the highest activity regarding prostaglandin E2 production with IC50 0.52 µM. The effect of the most potent compounds was tested by western blot against iNOS, COX-1, and COX-2.

Diterpenoids with Potent Anti-Psoriasis Activity from Euphorbia helioscopia L.

Psoriasis, an immune-mediated inflammatory skin disorder, seriously affects the quality of life of nearly four percent of the world population. Euphorbia helioscopia L. is the monarch constituent of Chinese ZeQi powder preparation for psoriasis, so it is necessary to illustrate its active ingredients. Thus, twenty-three diterpenoids, including seven new ones, were isolated from the whole herb of E. helioscopia L. Compounds 1 and 2, each featuring a 2,3-dicarboxylic functionality, are the first examples in the ent-2,3-sceo-atisane or the ent-2,3-sceo-abietane family. Extensive spectroscopic analysis (1D, 2D NMR, and HRMS data) and computational methods were used to confirm their structures and absolute configurations. According to the previous study and NMR data from the jatropha diterpenes obtained in this study, some efficient 1H NMR spectroscopic rules for assigning the relative configurations of 3α-benzyloxy-jatroph-11E-ene and 7,8-seco-3α-benzyloxy-jatropha-11E-ene were summarized. Moreover, the hyperproliferation of T cells and keratinocytes is considered a key pathophysiology of psoriasis. Anti-proliferative activities against induced T/B lymphocytes and HaCaT cells were tested, and IC50 values of some compounds ranged from 6.7 to 31.5 µM. Compounds 7 and 11 reduced the secretions of IFN-γ and IL-2 significantly. Further immunofluorescence experiments and a docking study with NF-κB P65 showed that compound 13 interfered with the proliferation of HaCaT cells by inhibiting the NF-κB P65 phosphorylation at the protein level.

Health-Promoting Properties of Pectin-Polyphenol Complex Extracted from Olive Oil By-Product Alperujo: Antioxidant, Antiproliferative, and Anti-Inflammatory Activities.

This research explores the health-promoting properties of the pectin-polyphenol complex extracted from alperujo, a by-product of olive oil production. This study investigates the chemical composition and antioxidant activity of the extracts, revealing their high antioxidant activity in vitro. Cell viability assays conducted on colon carcinoma cells (Caco-2) demonstrate the inhibitory effect of the extracts on cell proliferation. However, the extracts do not affect the viability of differentiated Caco-2 cells, suggesting a selective antiproliferative action. Additionally, the extracts reduce intracellular reactive oxygen species (ROS) and nitrite (NO) production in LPS-stimulated murine peritoneal macrophages. Furthermore, the extracts exhibit anti-inflammatory effects by downregulating the secretion of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in these macrophages. These findings highlight the potential of pectin-polyphenol complexes as functional ingredients with significant health benefits, demonstrating antioxidant, antiproliferative, and anti-inflammatory properties.

Design, synthesis and antitumor activity of novel 4-oxobutanamide derivatives.

To find highly effective and low-toxicity antitumor drugs to overcome the challenge of cancer, we designed and synthesized a series of novel 4-oxobutanamide derivatives using the principle of molecular hybridization and tested the antiproliferative ability of the title compounds against human cervical carcinoma cells (HeLa), human breast carcinoma cells (MDA-MB-231) and human kidney carcinoma cells (A498). Among them, N1-(4-methoxybenzyl)-N4-(4-methoxyphenyl)-N1-(3,4,5-trimethoxyphenyl) succinimide DN4 (IC50 = 1.94 µM) showed the best proliferation activity on A498, superior to the positive control paclitaxel (IC50 = 8.81 µM) and colchicine (IC50 = 7.17 µM). Compound DN4 not only inhibited the proliferation, adhesion and invasion of A498, but also inhibited angiogenesis and tumor growth in a dose-dependent manner in the xenograft model of A498 cells. In addition, we also predicted the physicochemical properties and toxicity (ADMET) of these derivatives, and the results suggested that these derivatives may have the absorption, distribution, metabolism, excretion, and toxicity properties of drug candidates. Thus, compound DN4 may be a promising drug candidate for the treatment of cancer.

Polymethoxylated flavone variations and in vitro biological activities of locally cultivated Citrus varieties in China.

Citrus peels are rich in polymethoxylated flavones (PMFs), which have beneficial health and pharmacological properties. In this study, the profiles, variations, and biological activities of PMFs in the peel extracts of 27 Citrus varieties (eight species) native to China were investigated. UPLC-QTOF-MS/MS analysis revealed that mandarin accumulated more diversity and higher detectable PMF contents. Wangcangzhoupigan (ZPG) possessed the highest antioxidant capacity. Gailiangcheng (GLC) and Bingtangcheng (BTC), sweet oranges showed excellent inhibitory effects against pancreatic lipase and α-glucosidase, respectively. Most citrus extracts effectively inhibited the production of ROS and pro-inflammatory cytokines, while increasing the accumulation of anti-inflammatory cytokines. In addition, Limeng (LM), Cupig-oushigan (GSG), and Yanxiwanlu (YXWL) showed anti-proliferative effects against DU145 and PC3 cancer cells. This study provides a comprehensive PMF profile and biological activities of various citrus species and will benefit future functional citrus breeding practices aimed at designing plants rich in total or specific PMFs for health benefits.