Epidemiological studies have shown that the consumption of a high-fat diet (HFD) is positively related to the development of obesity. Lycopene (LYC) can potentially combat HFD-induced obesity and metabolic disorders in rats. This study aimed to investigate the effect of LYC on metabolic syndrome and assess its anti-inflammatory and antioxidant effects on the liver and adipose tissue in rats fed an HFD. Thirty-six male Wistar albino rats were divided into three groups. Group Ι (the control group) was fed a normal diet, group ΙΙ (HFD) received an HFD for 16 weeks, and group ΙΙΙ (HFD + LYC) received an HFD for 12 weeks and then LYC (25 mg/kg b.wt) was administered for four weeks. Lipid peroxidation, antioxidants, lipid profile, liver function biomarkers, and inflammatory markers were determined. The results showed that long-term consumption of an HFD significantly increased weight gain, liver weight, and cholesterol and triglyceride levels. Rats on an HFD displayed higher levels of lipid peroxidation and inflammatory markers. Moreover, liver and white adipose tissue histopathological investigations showed that LYC treatment mended the damaged tissue. Overall, LYC supplementation successfully reversed HFD-induced changes and shifts through its antioxidant and anti-inflammatory activity. Therefore, LYC displayed a therapeutic potential to manage obesity and its associated pathologies. Full article

Aberrant accumulation of β-catenin in the cell nucleus as a result of deregulation of the Wnt/β-catenin pathway is found in various types of cancer. Direct β-catenin targeting agents are being researched despite obstacles; however, specific β-catenin drugs for clinical treatments have not been approved so far. We focused on direct β-catenin targeting of potential therapeutic value as anticancer agents. This review provides recent advances on small molecule β-catenin agents. Structure-activity relationships and biological activities of reported inhibitors are discussed. This work provides useful knowledge in the discovery of β-catenin agents. Full article

The genus Eremophila (family Scrophulariaceae) consists of approximately 200 species that are widely distributed in the semi-arid and arid regions of Australia. Multiple Eremophila spp. are used as traditional medicines by the First Australians in the areas in which they grow. They are used for their antibacterial, antifungal, antiviral, antioxidant, anti-diabetic, anti-inflammatory, and cardiac properties. Many species of this genus are beneficial against several diseases and ailments. The antibacterial properties of the genus have been relatively well studied, with several important compounds identified and their mechanisms studied. In particular, Eremophila spp. are rich in terpenoids, and the antimicrobial bioactivities of many of these compounds have already been confirmed. The therapeutic properties of Eremophila spp. preparations and purified compounds have received substantially less attention, and much study is required to validate the traditional uses and to highlight species that warrant further investigation as drug leads. The aim of this study is to review and summarise the research into the medicinal properties, therapeutic mechanisms, and phytochemistry of Eremophila spp., with the aim of focussing future studies into the therapeutic potential of this important genus. Full article

Bee pollen, because of its high content of nutrients, is a very valuable medicinal and nutritional product. However, since its composition is not completely studied, the consumption of this product may cause adverse effects, including allergic reactions. Therefore, this study aimed to discover and characterize the bioactive proteins of bee pollen collected in Poland, focusing mainly on the allergens. For this purpose, the purified and concentrated pollen aqueous solutions were analyzed using the nanoLC-MALDI-TOF/TOF MS analytical platform. As a result of the experiments, 197 unique proteins derived from green plants (Viridiplantae) and 10 unique proteins derived from bees (Apis spp.) were identified. Among them, potential plant allergens were discovered. Moreover, proteins belonging to the group of hypothetical proteins, whose expression had not been confirmed experimentally before, were detected. Because of the content of bioactive compounds—both beneficial and harmful—there is a critical need to develop guidelines for standardizing bee pollen, especially intended for consumption or therapeutic purposes. This is of particular importance because awareness of the allergen content of bee pollen and other bee products can prevent health- or life-threatening incidents following the ingestion of these increasingly popular “superfoods”. Full article

The severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2, is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 has a highly conserved non-structural protein 12 (NSP-12) involved in RNA-dependent RNA polymerase (RdRp) activity. For the identification of potential inhibitors for NSP-12, computational approaches such as the identification of homologous proteins that have been previously targeted by FDA-approved antivirals can be employed. Herein, homologous proteins of NSP-12 were retrieved from Protein DataBank (PDB) and the evolutionary conserved sequence and structure similarity of the active site of the RdRp domain of NSP-12 was characterized. The identified homologous structures of NSP-12 belonged to four viral families: Coronaviridae, Flaviviridae, Picornaviridae, and Caliciviridae, and shared evolutionary conserved relationships. The multiple sequences and structural alignment of homologous structures showed highly conserved amino acid residues that were located at the active site of the RdRp domain of NSP-12. The conserved active site of the RdRp domain of NSP-12 was evaluated for binding affinity with the FDA-approved antivirals, i.e., Sofosbuvir and Dasabuvir in a molecular docking study. The molecular docking of Sofosbuvir and Dasabuvir with the active site that contains conserved motifs (motif A-G) of the RdRp domain of NSP-12 revealed significant binding affinity. Furthermore, MD simulation also inferred the potency of Sofosbuvir and Dasabuvir. In conclusion, targeting the active site of the RdRp domain of NSP-12 with Dasabuvir and Sofosbuvir might reduce viral replication and pathogenicity and could be further studied for the treatment of SARS-CoV-2. Full article

Four new 2–3D materials were designed and synthesized by hydrothermal methods, namely, {[(L1·Cu·2H₂O) (4,4-bipy)_0.5] (β-Mo₈O₂₆)_0.5·H₂O} (1), {[(L1·Cu)₂·(4,4-bipy)] (Mo₅O₁₆)} (2), {Co(L1)₂}_n (3), and {[(L1)₂][β-Mo₈O₂₆]_0.5·5H₂O} (4). [L1=5-(4-aminopyridine) isophthalic acid]. The degradation of ciprofloxacin (CIP) in water by compounds 1–4 was studied under visible light. The experimental results show that compounds 1–4 have obvious photocatalytic degradation effect on CIP. In addition, for compound 1, the effects of temperature, pH, and adsorbent dosage on photocatalytic performance were also investigated. The stability of compound 1 was observed by a cycle experiment, indicating that there was no significant change after three cycles of CIP degradation. Full article

Viniferifuran was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid. An enzyme kinetics analysis showed that viniferifuran possessed a strong inhibition on XO in a typical anti-competitive manner with an IC₅₀ value of 12.32 μM (IC₅₀ for the first-line clinical drug allopurinol: 29.72 μM). FT-IR and CD data analyses showed that viniferifuran could induce a conformational change of XO with a decrease in the α-helix and increases in the β-sheet, β-turn, and random coil structures. A molecular docking analysis revealed that viniferifuran bound to the amino acid residues located within the activity cavity of XO by a strong hydrophobic interaction (for Ser1214, Val1011, Phe914, Phe1009, Leu1014, and Phe649) and hydrogen bonding (for Asn768, Ser876, and Tyr735). These findings suggested that viniferifuran might be a promising XO inhibitor with a favorable mechanism of action. Full article

Groundwater is one of the main sources of water for irrigation used worldwide. However, the application of the resource is threatened by the possibility of high saline levels, especially in low-lying coastal regions. Furthermore, the lack of readily accessible materials for successful treatment procedures makes the purification of such water a constant challenge. Based on the fact that natural zeolite is one of the easily accessible and relatively cheap filter materials, this study examined the potential use of high-salinity groundwater filtered by natural zeolite for irrigation. Zeolite-filled filters at two different depths (0.5 m and 1 m) were studied. The samples were collected from the low-lying areas of Dar es Salaam City, Tanzania. The study observed that when the raw groundwater samples were exposed to the 0.5 m column depth, sodium (Na⁺) had the lowest removal efficiency at 40.2% and calcium (Ca²⁺) had the highest removal efficiency at 98.9%. On the other hand, magnesium (Mg²⁺) had the lowest removal efficiency, at about 61.2%, whereas potassium (K⁺) had up to about 99.7% removal efficiency from the 1 m column depth treatment system. Additionally, from the salinity hazard potential analysis, most of the samples fell within C4 (based on the electrical conductivity), which is a “very high salinity” class, and based on the quality it means the water cannot be directly applied for irrigation purposes. From the 0.5 m column depth, most of the samples fell within C3 (the “high salinity” class), and from the 1 m column depth most of the samples fell within C1 (“low salinity” class). The findings of this study offer some valuable insight into the prospective use of natural zeolite for the filtration of saline groundwater before its application for irrigation. Full article

Cysteine is one of the least abundant amino acids in proteins of many organisms, which plays a crucial role in catalysis, signal transduction, and redox regulation of gene expression. The thiol group of cysteine possesses the ability to perform nucleophilic and redox-active functions that are not feasible for other natural amino acids. Cysteine is the most common covalent amino acid residue and has been shown to react with a variety of warheads, especially Michael receptors. These unique properties have led to widespread interest in this nucleophile, leading to the development of a variety of cysteine-targeting warheads with different chemical compositions. Herein, we summarized the various covalent warheads targeting cysteine residue and their application in drug development. Full article

The importance of the circadian clock in maintaining human health is now widely acknowledged. Dysregulated and dampened clocks may be a common cause of age-related diseases and metabolic syndrome Thus, circadian clocks should be considered as therapeutic targets to mitigate disease symptoms. This review highlights a number of dietary compounds that positively affect the maintenance of the circadian clock. Notably the polymethoxyflavone nobiletin has shown some encouraging results in pre-clinical experiments. Although many more experiments are needed to fully elucidate its exact mechanism of action, it is a promising candidate with potential as a chronotherapeutic agent. Full article

The growing problem of antibiotic resistance among bacteria requires searching for new therapeutic agents with bacteriostatic and/or bactericidal properties. Crotoxin is a β-neurotoxin from the venom of the Crotalus durissus terrificus. It is composed of two subunits: CA (non-active) and CB (with phospholipase A₂ activity). It has already been shown that the isolated CB, but not the CA, subunit of crotoxin exhibits an antibacterial activity towards a variety of Gram-positive and Gram-negative bacterial species. However, no studies on the whole crotoxin complex have been carried out so far. We tested the antibacterial properties of crotoxin, as well as its isolated CB subunit, towards Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 6535, Micrococcus luteus ATCC 10240, Escherichia coli ATCC 25922, Escherichia coli ATCC 8739, and Pseudomonas aeruginosa ATCC 10145. Both toxins exhibited antibacterial properties only against Micrococcus luteus ATCC 10240. Crotoxin showed only bacteriostatic activity with a MIC of 46 µM, while the CB subunit acted as both a bacteriostatic and bactericidal agent with a MIC = MBC = 0.21 μM. The bacteriostatic effect of the toxins was independent of the enzymatic activity of the CB subunit. Bactericidal properties, however, require phospholipase A₂ activity. Both toxins reduced bacteria viability at the MIC by 72% and 85% for crotoxin- and CB-treated bacteria, respectively. The membrane permeability increased approximately three times within the first hour of incubation with toxins; afterwards, either no significant changes or a decrease of membrane permeability, compared to the control cells, were observed. We isolated a single, approximately 30 kDa bacterial wall protein which belongs to the NlpC/P60 family that interacts with crotoxin leading to the inhibition of bacterial growth. Neither crotoxin nor the CB subunit showed any cytotoxic properties to human fibroblasts at the MIC during the three-day incubation. Full article

A series of potassium salts of di- and tri-arylsubstituted cyclopentadienes has been obtained by the metalation of the corresponding cyclopentadienes with benzylpotassium in THF media. Crystals of all compounds, afforded by recrystallization from THF/hexane, diglyme-THF/hexane and toluene/hexane mixtures, have been studied by X-ray diffraction. All studied potassium cyclopentadienides exhibit the luminescence at room temperature and overall quantum yield of photoluminescence for potassium salt of diarylsubstituted cyclopentadiene is 18%. Full article

Two LC methods were developed for the achiral and chiral reversed-phase (RP) analysis of an amino acid (AA) pool in a food supplement, in compliance with the main paradigms of Green Chromatography. A direct achiral ion-pairing RP-HPLC method was optimized under gradient conditions with a water-ethanol (EtOH) eluent containing heptafluorobutyric acid (0.1%, v/v), to quantify the eight essential AAs (Ile, Leu, Lys, Met, Phe, Thr, Trp, and Val) contained in the food supplement. Thus, the usually employed acetonitrile was profitably substituted with the less toxic and more benign EtOH. The method was validated for Leu and Phe. The chiral LC method performed with a teicoplanin chiral stationary phase was developed with a water-EtOH (60:40, v/v) eluent with 0.1%, v/v acetic acid. The enantioselective analysis was carried out without any prior derivatization step. Both developed methods performed highly for all eight AAs and revealed that: (i) the content of six out of eight AAs was consistent with the manufacturer declaration; (ii) only L-AAs were present. Furthermore, it was demonstrated that a two-dimensional achiral–chiral configuration is possible in practice, making it even more environmentally sustainable. A molecular modelling investigation revealed interesting insights into the enantiorecognition mechanism of Lys. Full article

Antiaris africana Engler leaves have been used in Senegalese folk medicine to treat breast cancer. The present study aimed to investigate the anticancer potential of Antiaris africana Engler leaves using several human cancer cell lines. The leaves of Antiaris africana Engler were extracted in parallel with water or 70% ethanol and each extract divided into three parts by successive liquid–liquid extraction with ethyl acetate and butanol. The phytochemical components of the active extract were investigated using ultra-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (UPLC-DAD-QTOF-MS/MS). The cytotoxic and cytostatic effects of each extract, as well as their fractions, were evaluated in vitro via flow and image cytometry on different human cancer phenotypes, such as breast (MCF-7), pancreas (AsPC-1), colon (SW-620) and acute monocytic leukemia (THP-1). Both hydro-alcoholic and aqueous extracts induced strong apoptosis in MCF-7 cells. The water fraction of the hydro-alcoholic extract was found to be the most active, suppressing the cell growth of MCF-7 in a dose-dependent manner. The half maximum effective concentration (EC₅₀) of this fraction was 64.6 ± 13.7 μg/mL for MCF-7, with equivalent values for all tested phenotypes. In parallel, the apoptotic induction by this fraction resulted in a EC₅₀ of 63.5 ± 1.8 μg/mL for MCF-7, with again equivalent values for all other cellular tested phenotypes. Analysis of this fraction by UPLC-DAD-QTOF-MS/MS led to the identification of hydroxycinnamates as major components, one rutin isomer, and three cardiac glycosides previously isolated from seeds and bark of Antiaris africana Engler and described as cytotoxic in human cancer models. These results provide supportive data for the use of Antiaris africana Engler leaves in Senegal. Full article

One of the powerful antioxidants used clinically is Edaravone (EDA). We synthesized a series of new EDA analogs, 4-aminopyrazol-5-ol hydrochlorides, including polyfluoroalkyl derivatives, via the reduction of 4-hydroxyiminopyrazol-5-ones. The primary antioxidant activity of the compounds in comparison with EDA was investigated in vitro using ABTS, FRAP, and ORAC tests. In all tests, 4-Amino-3-pyrazol-5-ols were effective. The lead compound, 4-amino-3-methyl-1-phenylpyrazol-5-ol hydrochloride (APH), showed the following activities: ABTS, 0.93 TEAC; FRAP, 0.98 TE; and ORAC, 4.39 TE. APH and its NH-analog were not cytotoxic against cultured normal human fibroblasts even at 100 μM, in contrast to EDA. According to QM calculations, 4-aminopyrazolols were characterized by lower gaps, IP, and η compared to 4-hydroxyiminopyrazol-5-ones, consistent with their higher antioxidant activities in ABTS and FRAP tests, realized by the SET mechanism. The radical-scavenging action evaluated in the ORAC test occurred by the HAT mechanism through OH bond breaking in all compounds, directly dependent on the dissociation energy of the OH bond. All the studied compounds demonstrated the absence of anticholinesterase activity and moderate inhibition of CES by some 4-aminopyrazolols. Thus, the lead compound APH was found to be a good antioxidant with the potential to be developed as a novel therapeutic drug candidate in the treatment of diseases associated with oxidative stress. Full article