In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate of panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed, and synthesized imidazolium RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including Oxygen Radical Absorbance Capacity, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging, Ferric Ion Reducing Antioxidant Power, Hydroxyl Radical Scavenging, and HA Fragmentation Assay. All results proved that imidazolium RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazolium RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active while compound 17, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds.

Purpose: To determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: Retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: Most patients, 83.3% (n=40), harboured macroadenomas and 31.3% (n=15) invasive pitu-itary adenomas. Fourteen patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60-120] and 20 [range 20-30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and un-treatred patients (P>0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanre-otide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR=4.64, P=0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR=0.65, P=0.570)), independently of the doses and the duration of SSA treatment (P>0.05). Conclusions: The dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

We propose a novel electrochemical system to form precipitation patterns of Cu-Fe-based Prussian blue analogues (Cu-Fe PBA) in agarose gels, using an applied voltage to produce reactant ions. The spatiotemporal evolution, spatial distribution, and crystallite morphologies of the precipitates were investigated by visual inspection, Fe Kα intensity distribution measurements, and optical and scanning electron microscope observations. The precipitation patterns and their evolution depended on the applied voltage. Multicolored periodic precipitation bands were stochastically formed under cyclic alternating voltage (4 V for 1 h and then 1 V for 4 h per cycle). The distances between adjacent bands were randomly distributed (0.30 ± 0.25 mm). The sizes and shapes of the crystallites generated in the gel were position-dependent. Almost cubic but fairly irregular crystallites (0.1–0.8 μm) were formed in the periodic bands, whereas definitely cube-shaped crystallites (1–3 μm) appeared close to the anode. These cube-like reddish-brown crystallites were assigned to Cu-FeII PBA. In some periodic bands, plate-like blue crystallites (assigned to Cu(OH)2) were also present. Future issues for applications of the observed periodic banding were discussed.

Curcumin, as the main active component of Turmeric (Curcuma Longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

The outbreak of novel coronavirus (COVID-19) infections in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking to repurpose HIV protease inhibitors and nucleoside analogues for COVID-19, with evaluations based on docking scores calculated by AutoDock Vina and RosettaCommons. Our results suggest that Indinavir and Remdesivir possess the best docking scores, and comparison of the docking sites of the two drugs reveal a near perfect dock in the overlapping region of the protein pockets. After further investigation of the functional regions inferred from the proteins of SARS coronavirus, we discovered that Indinavir does not dock on any active sites of the protease, which may give rise to concern in regards to the efficacy of Indinavir. On the other hand, the docking site of Remdesivir is not compatible with any known functional regions, including template binding motifs, polymerization motifs and nucleoside triphosphate (NTP) binding motifs. However, when we tested the active form (CHEMBL2016761) of Remdesivir, the docking site revealed a perfect dock in the overlapping region of the NTP binding motif. This result suggests that Remdesivir could be a potential therapeutic agent. Clinical trials still must be done in order to confirm the curative effect of these drugs.

Inhibitory activity of 14 phosphonic analogues of phenylglycine, substituted in aromatic ring by fluorine and chlorine, was determined towards porcine aminopeptidase N. The obtained data served as a basis for studying their interaction with the enzyme as modelled by the use of Schrödinger Release 2018 program. The observed linearity between modelled Gibbs free energy differences and inhibitory constants indicated the usefulness of this program. The obtained binding mode was compared with this modelled for bovine lens leucine aminopeptidase. Although both enzymes differ in the number of zinc ions present in the active site, they are considered to exhibit similar activity towards substrates and inhibitors. Our studies seem to support that supposition since the modes of binding of the studied inhibitors are quite similar. Additionally, inhibitory activity of the phosphonic analogues of phenylglycine towards barley aminopetpidase was determined showing that this enzyme could be considered as neutral aminopeptidase.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Because of the widespread use of bisphenol analogues (BPs) as the alternatives to bisphenol A (BPA), they have attracted considerable attention for health risk in aquatic ecosystems. The occurrence and distribution of six BPs were researched in soluble phase (< 5 kDa), colloidal phase (5 kDa to 1 µm) and suspended particulate matter (SPM > 1 µm) in a water diversion project of Nanjing, China. Except for bisphenol Z, all BPs were detected in the two or three phases, the total concentrations of detected BPs were 161-613 ng/L, 5.19-77.2 ng/L and 47.5-353 ng/g for the soluble phase, colloidal phase and SPM, respectively. Among the detected compounds, BPA still the dominant BPs in the soluble and colloidal phases, followed by BPS, while BPAF was the major contaminant in SPM, followed by BPA. The mean contribution proportions of colloids were 1-2 orders of magnitude higher than SPM, suggesting that colloids have an obvious impact on regulating BPs’ environmental behaviors. In terms of spatial distribution, although the water diversion project could reduce the pollution levels of BPs, which might further affect the ecological security of the Yangtze River.

Owing to the widespread use of bisphenol analogues (BPs) as bisphenol A (BPA) alternatives, they have been recognized to constitute a health risk for aquatic ecosystems. The occurrence and distribution of six BPs were investigated in the truly dissolved phase (< 5 kDa), colloidal phase (5 kDa to 1 µm) and suspended particulate matter (SPM > 1 µm) in a water diversion project of Nanjing, China. With the exception of bisphenol Z, all BPs were detected in at least two phases, the total concentrations of detected BPs were 161-613 ng/L, 5.19-77.2 ng/L and 47.5-353 ng/g for the truly dissolved phase, colloidal phase and SPM, respectively. Among the detected compounds, BPA still the dominant BPs in the truly dissolved phase and colloidal phase, followed by BPS, while BPAF was the major contaminant in SPM, followed by BPA. The mean contribution proportions of colloids were 1-2 orders of magnitude greater than that of SPM, suggesting that colloids play an important role in regulating the environmental behaviors of BPs. In terms of spatial distribution, although the water diversion project could reduce the pollution levels of BPs, which might further affect the ecological security of the Yangtze River.

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

Exposure to bisphenol analogues can occur in several ways throughout the food production chain with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22) including canned pineapples, ravioli and beer were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient quantitative simultaneous analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested with the most frequent analytes at higher concentrations; BPA and BPS being discovered in 78% and 48% of cases respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity.

In this article/review, the selective interactions of several berberine and palmatine derivatives with various DNA G-quadruplex structures are reported. These derivatives were constructed starting from two natural compounds, berberine and palamatine, through specific synthetic passages following two different schemes for each of them and using several substituents. The details of these synthesis are also described. Indeed, the study of the interactions of these derivative compounds with various G-quadruplex forming sequences was carried out by means of various structural and biochemical techniques. The results show that the presence of suitable side chains are very useful to improve the interaction of the ligands with G-quadruplex structures. Thus, since G-quadruplex formation is promoted by these compounds, which have never been reported before, these may be tested as potential anticancer drugs.

As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ^◦C were reduced by three orders of magnitude (from 10^-9 M to 10^-6 M) compared to the K d at 37 ^◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.