Pharmaceuticals

The worldwide emergence and dissemination of Gram-negative bacteria expressing metallo-β-lactamases (MBLs) menace the efficacy of all β-lactam antibiotics, including carbapenems, a last-line treatment usually restricted to severe pneumonia and urinary tract infections. Nonetheless, no MBL inhibitor is yet available in therapy. We previously identified a series of 1,2,4-triazole-3-thione derivatives acting as micromolar inhibitors of MBLs in vitro, but devoid of synergistic activity in microbiological assays. Here, via a multidisciplinary approach, including molecular modelling, synthesis, enzymology, microbiology, and X-ray crystallography, we optimized this series of compounds and identified low micromolar inhibitors active against clinically relevant MBLs (NDM-1- and VIM-type). The best inhibitors increased, to a certain extent, the susceptibility of NDM-1- and VIM-4-producing clinical isolates to meropenem. X-ray structures of three selected inhibitors in complex with NDM-1 elucidated molecular recognition at the base of potency improvement, confirmed in silico predicted orientation, and will guide further development steps. Full article

Background: Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes and thus contribute to chemotherapy-related anemia, which is extremely prevalent in cancer patients. Eriocitrin (ERN), a flavanone glycoside in citrus fruits, has shown great promise as an anticancer agent, but the potential toxicity of ERN to human erythrocytes remains unstudied. Methods: Erythrocytes were exposed to anticancer concentrations of ERN (10–100 μM) for 24 h at 37 °C, and hemolysis and associated markers were quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca²⁺ using Fluo4/AM, and oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H₂DCFDA). ERN was also tested against specific signaling inhibitors and anti-hemolytic agents. Results: ERN caused significant, concentration-dependent hemolysis at 20–100 μM. ERN also significantly increased the percentage of eryptotic cells characterized by Ca²⁺ elevation and oxidative stress. Furthermore, the hemolytic activity of ERN was significantly ameliorated in the presence of D4476, NSC23766, isosmotic urea and sucrose, and polyethylene glycol 8000 (PEG). In whole blood, ERN significantly elevated MCV and ESR, with no appreciable effects on other peripheral blood cells. Conclusions: ERN promotes premature erythrocyte death through hemolysis and eryptosis characterized by PS externalization, Ca²⁺ accumulation, membrane blebbing, loss of cellular volume, and oxidative stress. These toxic effects, mediated through casein kinase 1α and Rac1 GTPase, can be ameliorated by urea, sucrose, and PEG. Altogether, these novel findings are relevant to the further development of ERN as an anticancer therapeutic. Full article

Natural compounds such as gallic acid (GA) have attracted more attention in cosmetic and pharmaceutical skin care products. However, the low solubility and poor stability of GA have limited its application. This study aimed to synthesize and characterize the GA niosomal dispersion (GAN) and investigate the potential of an optimal formulation as a skin drug delivery system for GA. For this purpose, GAN formulations were synthesized using the thin layer evaporation method with different molar ratios of Tween 60/Span 60, along with a constant molar ratio of polyethylene glycol 4000 (PEG-4000) and cholesterol in a methanol and chloroform solvent (1:4 v/v). The physicochemical properties of nanosystems in terms of size, zeta potential, drug entrapment, drug release, morphology, and system–drug interaction were characterized using different methods. In addition, in vitro cytotoxicity, anti-tyrosinase activity, and antibacterial activity were evaluated by MTT assay, the spectrophotometric method, and micro-well dilution assay. All formulations revealed a size of 80–276 nm, polydispersity index (PDI) values below 0.35, and zeta potential values below—9.7 mV. F2 was selected as the optimal formulation due to its smaller size and high stability. The optimal formulation of GAN (F2) was as follows: a 1:1 molar ratio of Span 60 to cholesterol and 1.5 mM GA. The release of the F2 drug showed a biphasic pattern, which was fast in the first 12 h until 58% was released. Our results showed the high antibacterial activity of GAN against Escherichia coli and Pseudomonas aeruginosa. The MTT assay showed that GA encapsulation increased its effect on B6F10 cancer cells. The F2 formulation exhibited potent anti-tyrosinase activity and inhibited melanin synthesis. These findings suggest that it can be used in dermatological skin care products in the cosmetic and pharmaceutical industries due to its significant antibacterial, anti-melanoma, and anti-tyrosinase activity. Full article

The high energy of α emitters, and the strong linear energy transfer that goes along with it, lead to very efficient cell killing through DNA damage. Moreover, the degree of oxygenation and the cell cycle state have no impact on these effects. Therefore, α radioisotopes can offer a treatment choice to individuals who are not responding to β− or gamma-radiation therapy or chemotherapy drugs. Only a few α-particle emitters are suitable for targeted alpha therapy (TAT) and clinical applications. The majority of available clinical research involves ²²⁵Ac and its daughter nuclide ²¹³Bi. Additionally, the ²²⁵Ac disintegration cascade generates γ decays that can be used in single-photon emission computed tomography (SPECT) imaging, expanding the potential theranostic applications in nuclear medicine. Despite the growing interest in applying ²²⁵Ac, the restricted global accessibility of this radioisotope makes it difficult to conduct extensive clinical trials for many radiopharmaceutical candidates. To boost the availability of ²²⁵Ac, along with its clinical and potential theranostic applications, this review attempts to highlight the fundamental physical properties of this α-particle-emitting isotope, as well as its existing and possible production methods. Full article

The cannabinoid receptor 1 (CB1R) plays a pivotal role in regulating various physiopathological processes, thus positioning itself as a promising and sought-after therapeutic target. However, the search for specific and effective CB1R ligands has been challenging, prompting the exploration of drug repurposing (DR) strategies. In this study, we present an innovative DR approach that combines computational screening and experimental validation to identify potential Food and Drug Administration (FDA)-approved compounds that can interact with the CB1R. Initially, a large-scale virtual screening was conducted using molecular docking simulations, where a library of FDA-approved drugs was screened against the CB1R’s three-dimensional structures. This in silico analysis allowed us to prioritize compounds based on their binding affinity through two different filters. Subsequently, the shortlisted compounds were subjected to in vitro assays using cellular and biochemical models to validate their interaction with the CB1R and determine their functional impact. Our results reveal FDA-approved compounds that exhibit promising interactions with the CB1R. These findings open up exciting opportunities for DR in various disorders where CB1R signaling is implicated. In conclusion, our integrated computational and experimental approach demonstrates the feasibility of DR for discovering CB1R modulators from existing FDA-approved compounds. By leveraging the wealth of existing pharmacological data, this strategy accelerates the identification of potential therapeutics while reducing development costs and timelines. The findings from this study hold the potential to advance novel treatments for a range of CB1R -associated diseases, presenting a significant step forward in drug discovery research. Full article

Background: Diabetes mellitus (DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective, and green-synthesised nanoparticles as a medicinal therapy in the treatment of DM is an attractive option. Objective: In the present study, silver nanoparticles (AI-AgNPs) were biosynthesized through the green synthesis method using Azadirachta indica seed extract to evaluate their anti-diabetic potentials. Methods: These nanoparticles were characterized by using UV-visible spectroscopy, Fourier transform infrared spectrophotometers (FTIR), scanning electron microscopy (SEM), DLS, and X-ray diffraction (XRD). The biosynthesized AI-AgNPs and crude extracts of Azadirachta indica seeds were evaluated for anti-diabetic potentials using glucose adsorption assays, glucose uptake by yeast cells assays, and alpha-amylase inhibitory assays. Results: Al-AgNPs showed the highest activity (75 ± 1.528%), while crude extract showed (63 ± 2.5%) glucose uptake by yeast at 80 µg/mL. In the glucose adsorption assay, the highest activity of Al-AgNPs was 10.65 ± 1.58%, while crude extract showed 8.32 ± 0.258% at 30 mM, whereas in the alpha-amylase assay, Al-AgNPs exhibited the maximum activity of 73.85 ± 1.114% and crude extract 65.85 ± 2.101% at 100 µg/mL. The assay results of AI-AgNPs and crude showed substantial dose-dependent activities. Further, anti-diabetic potentials were also investigated in streptozotocin-induced diabetic mice. Mice were administered with AI-AgNPs (10 to 40 mg/kg b.w) for 30 days. Conclusions: The results showed a considerable drop in blood sugar levels, including pancreatic and liver cell regeneration, demonstrating that AI-AgNPs have strong anti-diabetic potential. Full article

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide and the third most common cause of cancer-related death. Several liver-targeted intra-arterial therapies are available for unresectable HCC, including selective internal radiation therapy (SIRT) and trans-arterial chemoembolization (TACE). Those two are the most used treatment modalities in localized non-operable HCC. TACE is the treatment option for patients with stage B, according to the BCLC staging system. In contrast, SIRT does not have an official role in the treatment algorithm, but recent studies showed promising outcomes in patients treated with SIRT. Although TACE is globally a safe procedure, it might provoke several vascular complications such as spasms, inflammatory constriction, and, in severe cases, occlusion, dissection, or collateralization. Hence, it is acclaimed that those complications could restrain the targeted response of the radio-embolization when we use it as second-line therapy post TACE. In this study, we will assess the efficacity of SIRT using Yttrium 90 Microspheres post incomplete or failure response to TACE. In our retrospective study, we had 23 patients who met the inclusion criteria. Furthermore, those patients have been followed radiologically and biologically. Then, we evaluated the therapeutic effect according to the mRECIST criteria, in addition to the personalized dose analysis. We found 8 patients were treated with TheraSphere^®, with a median tumor absorbed dose of 445 Gy, while 15 received SIR-Spheres^® treatment with a mean tumor dose of 268 Gy. After radiological analysis, 56.5% of the patients had a complete response, and 17.3% showed partial response, whereas 13% had stable disease and 13% had progressive disease. For patients treated with SIRT after an incomplete response or failure to TACE, we found an objective response rate of 73.8%. Despite the known vascular complications of TACE, SIRT can give a favorable response. Full article

The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic DNA-sensing systems that is activated in response to viral invasion and/or damage to the integrity of the nuclear envelope. The key outcome of this pathway is the production of interferon, which subsequently stimulates the transcription of hundreds of genes. In oncology, the situation is complex because this pathway may serve either anti- or pro-oncogenic roles, depending on context. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as DNA released from ruptured micronuclei, it results in the production of interferon, which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in terms of its association with cancer progression, giving special attention to pancreatic ductal adenocarcinoma and gliomas. As the development of new cGAS–STING-modulating small molecules and immunotherapies such as oncolytic viruses involves serious challenges, we highlight several recent fundamental discoveries, such as the proton-channeling function of STING. These discoveries may serve as guiding lights for potential pharmacological advancements. Full article

Two fucosylated chondroitin sulfates were isolated from the sea cucumbers Psolus peronii and Holothuria nobilis using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their composition was characterized in terms of quantitative monosaccharide and sulfate content, and structures were mainly elucidated using 1D- and 2D-NMR spectroscopy. As revealed by the data of the NMR spectra, both polysaccharides along with the usual fucosyl branches contained rare disaccharide branches α-D-GalNAc4S6R-(1→2)-α-L-Fuc3S4R→ attached to O-3 of the GlcA of the backbone (R = H or SO₃⁻). The polysaccharides were studied as stimulators of hematopoiesis in vitro using mice bone marrow cells as the model. The studied polysaccharides were shown to be able to directly stimulate the proliferation of various progenitors of myelocytes and megakaryocytes as well as lymphocytes and mesenchymal cells in vitro. Therefore, the new fucosylated chondroitin sulfates can be regarded as prototype structures for the further design of GMP-compatible synthetic analogs for the development of new-generation hematopoiesis stimulators. Full article

Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8⁺ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes. Full article

Biocompatible drug-delivery systems for soft tissue applications are of high interest for the medical and pharmaceutical fields. The subject of this research is the development of hydrogels loaded with bioactive compounds (inulin, thyme essential oil, hydro-glycero-alcoholic extract of Vitis vinifera, Opuntia ficus-indica powder, lactic acid, citric acid) in order to support the vaginal microbiota homeostasis. The nanofibrillar phyto-hydrogel systems developed using the biocompatible polymers chitosan (CS), never-dried bacterial nanocellulose (NDBNC), and Poloxamer 407 (PX) incorporated the water-soluble bioactive components in the NDBNC hydrophilic fraction and the hydrophobic components in the hydrophobic core of the PX fraction. Two NDBNC-PX hydrogels and one NDBNC-PX-CS hydrogel were structurally and physical-chemically characterized using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and rheology. The hydrogels were also evaluated in terms of thermo-responsive properties, mucoadhesion, biocompatibility, and prebiotic and antimicrobial effects. The mucin binding efficiency of hydrogel base systems was determined by the periodic acid/Schiff base (PAS) assay. Biocompatibility of hydrogel systems was determined by the MTT test using mouse fibroblasts. The prebiotic activity was determined using the probiotic strains Limosilactobacillus reuteri and Lactiplantibacillus plantarum subsp. plantarum. Antimicrobial activity was also assessed using relevant microbial strains, respectively, E. coli and C. albicans. TEM evidenced PX micelles of around 20 nm on NDBNC nanofibrils. The FTIR and XRD analyses revealed that the binary hydrogels are dominated by PX signals, and that the ternary hydrogel is dominated by CS, with additional particular fingerprints for the biocompounds and the hydrogel interaction with mucin. Rheology evidenced the gel transition temperatures of 18–22 °C for the binary hydrogels with thixotropic behavior and, respectively, no gel transition, with rheopectic behavior for the ternary hydrogel. The adhesion energies of the binary and ternary hydrogels were evaluated to be around 1.2 J/m² and 9.1 J/m², respectively. The hydrogels exhibited a high degree of biocompatibility, with the potential to support cell proliferation and also to promote the growth of lactobacilli. The hydrogel systems also presented significant antimicrobial and antibiofilm activity. Full article

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for α_vβ₃ integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation. Furthermore, the therapeutic properties of the [¹⁹⁸Au]AuNPs were evaluated in vitro on U87MG cells in terms of cell survival, suggesting that these [¹⁹⁸Au]AuNPs are a useful basis for future therapeutic concepts. Full article

Citrus, which belongs to the Rutaceae family, is a very widespread genus in the Mediterranean Basin. In Tunisia, various parts of these spontaneous or cultivated plants are used in common dishes or in traditional medicine. The purpose of this work was to investigate C. limon and C. paradisi essential oil (EO). The samples were studied for their chemical composition using SPME/MS, as well as their antibacterial and antifungal activities. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) methods were used to evaluate the anticoagulant potentialities. The obtained results show that both essential oils are rich in monoterpenes hydrocarbons, whereby limonene is the main compound in C. paradisi EO (86.8%) and C. limon EO (60.6%). Moreover, C. paradisi EO contains β-pinene (13.3%), sabinene (2.2%) and α-pinene (2.1%). The antibacterial assay of the essential oils showed important bactericidal and fungicidal effects against all strains tested. In fact, the MICs values of C. limon EO ranged from 0.625 to 2.5 mg/mL against all Gram-positive and Gram-negative bacteria, and from 6.25 to 12.5 mg/mL for Candida spp. strains, while C. paradisi EO was more active against all bacteria with low MICs values ranging from 0.192 to 0.786 mg/mL, and about 1.5 mg/mL against Candida species. Both tested Citrus EOs exhibited interesting anticoagulant activities as compared to heparin. The molecular docking approach was used to study the binding affinity and molecular interactions of all identified compounds with active sites of cytidine deaminase from Klebsiella pneumoniae (PDB: 6K63) and the C (30) carotenoid dehydrosqualene synthase from Staphylococcus aureus (PDB: 2ZCQ). The obtained results show that limonene had the highest binding score of −4.6 kcal.mol⁻¹ with 6K63 enzyme, and −6.7 kcal.mol⁻¹ with 2ZCQ receptor. The ADME profiling of the major constituents confirmed their important pharmacokinetic and drug-like properties. Hence, the obtained results highlight the potential use of both C. limon and C. paradisi essential oils as sources of bioactive compounds with antibacterial, antifungal, and anti-coagulant activities. Full article

Artur Silva’s research group has a long history in the field of medicinal chemistry. The development of new synthetic methods for oxygen (mostly polyphenols, e.g., 2- and 3-styrylchromones, xanthones, flavones) and nitrogen (e.g., pyrazoles, triazoles, acridones, 4-quinolones) heterocyclic compounds in order to be assessed as antioxidant, anti-inflammatory, antidiabetic, and anticancer agents has been the main core work of our research interests. Additionally, the synthesis of steroid-type compounds as anti-Alzheimer drugs as well as of several chromophores as important dyes for cellular imaging broadened our research scope. In this review article, we intend to provide an enlightened appraisal of all the bioactive compounds and their biological properties that were synthesized and studied by our research group in the last two decades. Full article

A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1–17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied range of inhibitory activities having IC₅₀ values ranging from 0.86 ± 0.33 μM to 26.73 ± 0.84 μM (AChE) and 0.89 ± 0.12 μM to 27.08 ± 0.19 μM (BuChE), respectively. The results obtained were compared with standard Donepezil drugs (IC₅₀ = 1.26 ± 0.18 μM for AChE) and (1.35 ± 0.37 μM for BuChE), respectively. Specifically, the derivatives 1–17, 1, 9, and 14 were found to be significantly active, with IC₅₀ values of 0.86 ± 0.30, 0.92 ± 0.10, and 1.10 ± 0.37 μM (against AChE) and 0.89 ± 0.12, 0.98 ± 0.48 and 1.19 ± 0.42 μM (against BuChE), respectively.The structure–activity relationship (SAR) studies revealed that derivatives bearing para-CF₃, ortho-OH, and para-F substitutions on the phenyl ring attached to the thiadiazole skeleton, as well as meta-Cl, -NO₂, and para-chloro substitutions on the phenyl ring, having a significant effect on inhibitory potential. The synthesized scaffolds have been further characterized by using ¹H-NMR, ¹³C-NMR, and (HR-MS) to confirm the precise structures of the synthesized compounds. Additionally, the molecular docking approach was carried out for most active compounds to explore the binding interactions established by most active compounds, with the active sites of targeted enzymes and obtained results supporting the experimental data. Full article

Ruan Hua Tang (RHT) and Ruan Hua Fang (RHF) are two Chinese herbal mixtures that have been used in clinical cancer treatment for decades. This study validated our hypothesis that RHT and RHF can inhibit lung tumor development in the mouse model of Benzo(a)pyrene-induced lung tumorigenesis. An RHT oral solution was diluted to 9% and 18% in water. RHF was mixed into the diet at 15% and 30% of total food in the final doses. Two weeks after injecting BP into mice, we administered RHT and RHF for eighteen weeks. We found that 9% and 18% RHT reduced tumor multiplicity by 36.05% and 38.81% (both p < 0.05) and the tumor load by 27.13% and 55.94% (p < 0.05); 15% and 30% RHF inhibited tumor multiplicity by 12.75% and 39.84% (p < 0.01) and the tumor load by 18.38% and 61.68% (p < 0.05). Ki67 expressions in the 9% and 18% RHT groups were 19.55% and 11.51%, significantly lower than in the control (33.64%). The Ki67 levels in the 15% and 30% RHF groups were 15.56% and 14.04%, significantly lower than in the control (27.86%). Caspase 3 expressions in the 9% and 18% RHT groups were 5.24% and 7.32%, significantly higher than in the control (2.39%). Caspase 3 levels in the 15% and 30% RHF groups were 6.53% and 4.74%, significantly higher than in the control (2.07%). The bio-absorption was confirmed via a pharmacokinetic test. This study showed that RHT and RHF are safe and can inhibit lung tumor development, with anti-proliferative and pro-apoptotic effects. Full article

Background: Pain can have a serious impact on a patient’s physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans. Methods: Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots. Results: Sixteen eligible articles, including k = 5 studies of pain tolerance (n = 210), k = 5 studies of pain threshold (n = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges’ g = 0.28, 95% CI = 0–0.55, Z = 1.99, p = 0.05) and pain tolerance (Hedges’ g = 0.32, 95% CI = 0.05–0.59, Z = 2.30, p = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of −0.37 (95% CI = −0.77 to 0.03, Z = −1.80) but with no statistical significance (p = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges’ g = 0.37, 95% CI = 0.29–0.64, Z = 5.33, p < 0.01). Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine. Full article

Several studies have examined the use of positron emission tomography (PET) using [⁶⁸Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients. Full article