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Neuroendocrine neoplasms (NENs) are a diverse group of malignancies with a shared phenotype but varying prognosis and response to current treatments. Based on their morphological features and rate of proliferation, NENs can be classified into two main groups with a distinct clinical behavior and response to treatment: (i) well-differentiated neuroendocrine tumors (NETs) or carcinoids (with a low proliferation rate), and (ii) poorly differentiated small- or large-cell neuroendocrine carcinomas (NECs) (with a high proliferation rate). For certain NENs (such as pancreatic tumors, higher-grade tumors, and those with DNA damage repair defects), chemotherapy is the main therapeutic approach. Among the different chemotherapic agents, cisplatin and carboplatin, in combination with etoposide, have shown the greatest efficacy in treating NECs compared to NETs. The cytotoxic effects of cisplatin and carboplatin are primarily due to their binding to DNA, which interferes with normal DNA transcription and/or replication. Consistent with this, NECs, which often have mutations in pathways involved in DNA repair (such as Rb, MDM2, BRCA, and PTEN), have a high response to platinum-based chemotherapy. Identifying mutations that affect molecular pathways involved in the initiation and progression of NENs can be crucial in predicting the response to platinum chemotherapy. This review aims to highlight targetable mutations that could serve as predictors of therapeutic response to platinum-based chemotherapy in NENs. [ABSTRACT FROM AUTHOR]

Platinum‐based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water‐soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1‐C2H4OEt)(phen)] (1, phen=1,10‐phenanthroline) precursor, specifically [Pt(NH3)(η1‐C2H4OEt)(phen)]Cl (2), [Pt(1‐hexyl‐1H‐imidazole)(η1‐C2H4OEt)(phen)]Cl (3), and [Pt(1‐hexyl‐1H‐benzo[d]imidazole)(η1‐C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki‐1), and normal human renal cells (HK‐2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki‐1) among the tested complexes, compared to healthy cells (HK‐2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum‐based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties. [ABSTRACT FROM AUTHOR]

Organic products are gaining popularity due to their positive impact on human health and the environment. While hydroponics is commonly used in vegetable production, it relies on mineral fertilizers derived from limited and non-renewable resources. As a result, farmers are actively seeking sustainable farming solutions. This study comprehensively evaluated the effectiveness of vermi-liquids (organic nutrient solutions) as a replacement for conventional inorganic nutrient solutions in promoting growth and nutrient acquisition in Diplotaxis muralis plants in a controlled environment. The results showed that plant biomass and SPAD values of D. muralis grown in Hoagland solution and enhanced vermitea (vermitea having relatively low pH and high EC) were higher compared to standard vermitea (high pH and low EC). The findings also revealed improved nutrient assimilation of phosphorus, potassium, calcium, iron, manganese, copper, and zinc in the enhanced vermitea plants. The heavy metal contents in D. muralis leaves were evaluated, too, and they were found to fall significantly below the safe threshold, rendering them safe for human consumption. However, the standard vermitea, with its high pH and low EC, performed poorly as a hydroponic solution. This research suggests that enhanced vermitea can completely replace chemical nutrient solutions in hydroponic agriculture. This substitution could lead to reduced production costs and improved product quality. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most lethal malignancies with an increasing incidence and a high mortality rate, due to its rapid progression, invasiveness, and resistance to anticancer therapies. In this work, we evaluated the antiproliferative and antimigratory activities of the two organometallic compounds, [Pt(η1-C2H4-OMe)(DMSO)(phen)]Cl (1) and [Pt(η1-C2H4-OEt)(DMSO)(phen)]Cl (2), on three human pancreatic ductal adenocarcinoma cell lines with different sensitivity to cisplatin (Mia PaCa-2, PANC-1, and YAPC). The two cationic analogues showed superimposable antiproliferative effects on the tested cells, without significant differences depending on alkyl chain length (Me or Et). On the other hand, they demonstrated to be more effective than cisplatin, especially on YAPC cancer cells. For the interesting cytotoxic activity observed on YAPC, further biological assays were performed, on this cancer cell line, to evaluate the apoptotic and antimetastatic properties of the considered platinum compounds (1 and 2). The cytotoxicity of 1 and 2 compounds appeared to be related to their intracellular accumulation, which was much faster than that of cisplatin. Both 1 and 2 compounds significantly induced apoptosis and cell cycle arrest, with a high accumulation of sub-G1 phase cells, compared to cisplatin. Moreover, phenanthroline-containing complexes caused a rapid loss of mitochondria membrane potential, ΔΨM, if compared to cisplatin, probably due to their cationic and lipophilic properties. On 3D tumor spheroids, 1 and 2 significantly reduced migrated area more than cisplatin, confirming an antimetastatic ability. [ABSTRACT FROM AUTHOR]

Environmental pollution has become a pressing concern worldwide due to the accumulation of pollutants from industries and agricultural sectors in soil and water environments. Heavy metals pose severe hazards to the environment, plants, and human health. Consequently, an eco-friendly technique is needed to combat environmental pollutants. Vermibiochar, a product prepared through the combined action of earthworms and biochar, demonstrates great potential in reducing heavy metal concentrations in contaminated soil. Its large surface area and high cation exchange capacity enhance the sorption of contaminants onto the vermibiochar surface, reducing their bioavailability. This review highlights the roles played by earthworms and biochar in heavy metal detoxification and immobilization. It discusses the current methods of remediation, vermibiochar production, its effects on soil properties and plant growth, and biochar's impact on earthworm growth and reproduction. The studies reviewed suggest that vermibiochar is a novel strategy for addressing heavy metal contamination. [ABSTRACT FROM AUTHOR]

NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ1-C2H4OMe)(DMSO)(phen)]+ (phen = 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH-SY5Y). In this study, the mechanism of action of Pt-EtOMeSOphen on SH-SY5Y cells was investigated using 1H NMR-based metabolomics and compared with cisplatin. The observed time response of SH-SY5Y cells under treatment revealed a faster action of Pt-EtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR-based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression. [ABSTRACT FROM AUTHOR]

This correction notice addresses an error in a previous publication in the journal Agronomy. The correction involves replacing reference number 34 in the References section with the correct citation. The authors assure readers that the scientific conclusions of the original publication remain unaffected. The correction has been approved by the Academic Editor and the original publication has been updated. [Extracted from the article]

Pomegranate peel extract is rich of interesting bioactive chemicals, principally phenolic compounds, which have shown antimicrobial, anticancer, and antioxidative properties. The aim of this work was to improve extract' bioactivity through the adsorption on calcium carbonate nanocrystals. Nanocrystals revealed as efficient tools for extract adsorption reaching 50% of loading efficiency. Controlled release of the contained metabolites under acidic pH has been found, as it was confirmed by quantitative assay and qualitative study through NMR analysis. Specific functionality of inorganic nanocarriers could be also tuned by biopolymeric coating. The resulting coated nanoformulations showed a great antimicrobial activity against B. cinerea fungus preventing strawberries disease better than a commercial fungicide. Furthermore, nanoformulations demonstrated a good antiproliferative activity in neuroblastoma and breast cancer cells carrying out a higher cytotoxic effect respect to free extract, confirming a crucial role of nanocarriers. Finally, pomegranate peel extract showed a very high radical scavenging ability, equal to ascorbic acid. Antioxidant activity, measured also in intracellular environment, highlighted a protective action of extract-adsorbed nanocrystals twice than free extract, providing a possible application for new nutraceutical formulations. [ABSTRACT FROM AUTHOR]

By studying a model set of square‐planar [Pt(NH3)aXb]n (a + b = 4; Xb = combination of b halido ligands; n = 2 – b) complexes, we found that their δ(195Pt) NMR chemical shift decreases proportionally to the platinum bonded halido ligands' ionic radii overall sum. This confirms also for these systems, the already observed NMR shielding attributed to pseudo ring currents, circulating around the M–X bond axis. Moreover, the present data show that also the NH3 ligands are characterized by a constant NMR shielding ability toward the central metal. This could be rationalized in term of a "NMR effective molecular radius" of the NH3 ligand, affecting the observed δ(195Pt) as previously found for halido ligands. Interestingly, a δ(15N) decrease is observed in Pt bonded NH3 ligands if the ionic radius of a cis halido ligand is increased. The opposite occurs if the ionic radius of a trans halido ligand is increased. The two contrasting effects stem from both shielding electric ring currents affecting the cis ligands and prevailing trans‐influence due to coordinated halido ligands. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the δ NMR chemical shift of central NMR active atoms (A), in simple halido [AXn] (A=C, Si, Ge, Sn, Pb, Pt; Xn = combination of n halides, n = 4 or 6) derivatives, could be directly related to X radii overall sum, Σ(rL). Further correlation have also been observed for tetrahedral [AX4] (A=C, Si; X4 = combination of four halides) compounds where the X Pauling electronegativities sum, Σ (χ L Pau) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ exceeds a specific value (≈12.4). In this work, we focused on these latter systems considering the H vs. X substitution. The analysis of the literature reported δ(13C) and δ(29Si) NMR chemical shift for the mono hydrogenated derivatives and in particular for [CHF3] and [SiHF3], characterized by the lowest Σ(rL) and the highest Σ (χ L Pau) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ suggests a revised value for the H electronegativity ranking with respect to Pauling's. [ABSTRACT FROM AUTHOR]

The novel [Pt(O,O'-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of cis-[PtCl2(NH3)2], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A ¹H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC50 doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells. [ABSTRACT FROM AUTHOR]

The reactivity of [PtX2(Me2phen)] complexes (X = Cl, Br, I; Me2phen = 2,9-dimethyl-1,10-phenanthroline) with terminal alkynes has been investigated. Although the dichlorido species [PtCl2(Me2phen)] exhibits negligible reactivity, the bromido and iodido derivatives lead in short time to the formation of five-coordinate Pt(ii) complexes of the type [PtX2(Me2phen)(η2-CH≡CR)] (X = Br, I; R = Ph, n-Bu), in equilibrium with the starting reagents. Similar to analogous complexes with simple acetylene, the five coordinate species can also undergo dissociation of an halido ligand and formation of the transient square-planar cationic species [PtX(Me2phen)(η2-CH≡CR)]+. This latter can further evolve to give an unusual, sparingly soluble square planar product where the former terminal alkyne is converted into a :C=C(H)(R) moiety with the α-carbon bridging the Pt(ii) core with one of the two N-donors of coordinated Me2phen. The final product [PtX2{κ2-N,C-(Z)-Ṉ1–N10–C̱=C(H)(R)}] (N1–N10 = 2,9-dimethyl-1,10-phenanthroline; X = Br, I) contains a Pt–N–C–C–N–C six-membered chelate ring in a square planar Pt(ii) coordination environment. [ABSTRACT FROM AUTHOR]

In carbon and silicon tetrahalide compounds, the experimental 13C and 29Si NMR chemical-shift values are known to increase or decrease on increasing the overall sum of the ionic radii of the bonded halides Σ( rh) (normal and inverse halogen dependence (NHD and IHD, respectively)). Herein, we extrapolate the main factors responsible for such NMR chemical shifts. Intriguingly, we found a characteristic value for the overall sum of the Pauling electronegativities of the bonded halides Σ( χh), which works as a triggering factor to determine the transition from the NHD to IHD. Below this Σ( χh) value, the chemical shift of the central atom was strictly related to only the Σ( rh) value, thus producing a NHD trend. Conversely, above this value, the chemical shift of the central atom was dependent on both the Σ( rh) and Σ( χh) values, thus producing a IHD trend. A simple model, in which the effect of the Σ( χh) value on 13C and 29Si NMR chemical shifts is related to an apparent increase in the Σ( rh) value, is deduced. [ABSTRACT FROM AUTHOR]

In this work, we show by a simple empirical approach that a linear relationship between observed 195Pt NMR frequencies and the overall sum of the ionic radii of the coordinated halido ligands [Σ( rh)] exists in square-planar PtII complexes of the type [PtX nY4- n]2- (1 ≤ n ≤ 4; X, Y = Cl, Br, I). Another finding was that such square-planar complexes could be empirically described as octahedral complexes, with the two lobes of the 5d z² orbital above and below the coordination plane acting as two pseudo-halido ligands, each showing a constant apparent radius of around 207 pm. According to our approach, the overall apparent radius of around 415 pm produces constant 195Pt NMR shielding for all [PtX nY4- n]2- complexes of about 10450 ppm. This result is 1) consistent with the theoretically calculated overall 5d shell lone-pair shielding observed in square-planar PtII with respect to octahedral PtIV complexes and 2) almost coincident with the already measured chemical shift anisotropy (CSA) of the K2[PtCl4] complex both in solution and in the solid state (single crystal). [ABSTRACT FROM AUTHOR]

Starting from the [PtCl(η1-C2H4OMe)(phen)] (phen = 1,10-phenanthroline, 1) platinum(II) precursor, we synthesized and characterized by multinuclear NMR new [Pt(η1-C2H4OMe)(L)(phen)]+ (L = NH3, 2; DMSO, 3) complexes. These organometallic species, potentially able to interact with cell membrane organic cation transporters (OCT), violating some of the classical rules for antitumor activity of cisplatin analogues, were evaluated for their cytotoxicity. Interestingly, despite both complexes 2 and 3 resulting in greater cell uptake than cisplatin in selected tumor cell lines, only 3 showed comparable or higher antitumor activity. General low cytotoxicity of complex 2 in the tested cell lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-65) appeared to depend on its stability towards solvolysis in neutral water, as assessed by NMR monitoring. Differently, the [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (3) complex was easily hydrolyzed in neutral water, resulting in a comparable or higher cytotoxicity in cancer cells with respect to cisplatin. Further, both IC50 values and the uptake profiles of the active complex appeared quite different in the used cell lines, suggesting the occurrence of diversified biological effects. Nevertheless, further studies on the metabolism of complex 3 should be performed before planning its possible use in tissue- and tumor-specific drug design. [ABSTRACT FROM AUTHOR]