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World Journal of Gastroenterology May 2024The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of...
BACKGROUND
The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated.
AIM
To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC.
METHODS
We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.
RESULTS
The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs).
CONCLUSION
The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Fluorouracil; Infusions, Intra-Arterial; Leucovorin; Aged; Adult; Hepatic Artery; Organoplatinum Compounds; Treatment Outcome; Molecular Targeted Therapy; Progression-Free Survival; Retrospective Studies; Immunotherapy; Combined Modality Therapy
PubMed: 38813052
DOI: 10.3748/wjg.v30.i17.2321 -
RSC Advances May 2024Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider... (Review)
Review
Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider range of pharmacological applications such as antitumor, antioxidant, anti-HIV, antifungal, anti-inflammatory, and antimicrobial properties. A lot of research has been carried out on chromone-based copper(ii) Schiff-base complexes owing to their role in the organometallic domain and promise as potential bioactive cores. This review article is centered on copper(ii) Schiff-base complexes derived from chromones, highlighting their diverse range of pharmacological applications documented in the past decade, as well as the future research opportunities they offer.
PubMed: 38808245
DOI: 10.1039/d4ra00590b -
International Journal of Nanomedicine 2024The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in...
PURPOSE
The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.
PATIENTS AND METHODS
To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.
RESULTS
The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against HO-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.
CONCLUSION
The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.
Topics: Animals; Indoles; Polymers; Kaempferols; Mice; Nanoparticles; Oxidative Stress; Metal-Organic Frameworks; Blood-Brain Barrier; Cell Line; Reactive Oxygen Species; Postoperative Cognitive Complications; Humans; Male; Neurons; Hydrogen Peroxide
PubMed: 38799697
DOI: 10.2147/IJN.S455492 -
Frontiers in Immunology 2024The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial...
BACKGROUND
The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC.
MATERIALS AND METHODS
Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs).
RESULTS
A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs.
CONCLUSION
Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Female; Phenylurea Compounds; Middle Aged; Quinolines; Aged; Cholangiocarcinoma; Antibodies, Monoclonal; Bile Duct Neoplasms; Infusions, Intra-Arterial; Leucovorin; Adult; Fluorouracil; Treatment Outcome; Organoplatinum Compounds; Hepatic Artery; Retrospective Studies
PubMed: 38799453
DOI: 10.3389/fimmu.2024.1397827 -
Journal of Nanobiotechnology May 2024Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar...
Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment's impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel's synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.
Topics: Periodontitis; Hydrogels; Bone Regeneration; Metal-Organic Frameworks; Animals; Chitosan; Mice; Drug Delivery Systems; Dextrans; Male; Reactive Oxygen Species; Anti-Bacterial Agents; Delayed-Action Preparations; Humans
PubMed: 38797862
DOI: 10.1186/s12951-024-02555-9 -
Journal of Cancer Research and Clinical... May 2024Somatostatin receptor (SSTR)-targeted PET imaging has emerged as a common approach to evaluating those patients with well-differentiated neuroendocrine tumors (NETs)....
PURPOSE
Somatostatin receptor (SSTR)-targeted PET imaging has emerged as a common approach to evaluating those patients with well-differentiated neuroendocrine tumors (NETs). The SSTR reporting and data system (SSTR-RADS) version 1.0 provides a means of categorizing lesions from 1 to 5 according to the likelihood of NET involvement, with SSTR-RADS-3A (soft-tissue) and SSTR-RADS-3B (bone) lesions being those suggestive of but without definitive NET involvement. The goal of the present study was to assess the ability of Ga-DOTATATE PET/MR imaging data to predict outcomes for indeterminate SSTR-RADS-3A and 3B lesions.
METHODS
NET patients with indeterminate SSTR-RADS-3A or SSTR-RADS-3B lesions who underwent Ga-DOTATATE PET/MR imaging from April 2020 through August 2023 were retrospectively evaluated. All patients underwent follow-up through December 2023 (median, 17 months; (3-31 months)), with imaging follow-up or biopsy findings ultimately being used to classify lesions as malignant or benign. Lesion maximum standardized uptake value (SUVmax) along with minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) values were measured and assessed for correlations with outcomes on follow-up.
RESULTS
In total, 33 indeterminate SSTR-RADS-3 lesions from 22 patients (19 SSTR-RADS-3A and 14 SSTR-RADS-3B) were identified based upon baseline Ga-DOTATATE PET/MR findings. Over the course of follow-up, 16 of these lesions (48.5%) were found to exhibit true NET positivity, including 9 SSTR-RADS-3A and 7 SSTR-RADS-3B lesions. For SSTR-RADS-3A lymph nodes, a diameter larger than 0.7 cm and an ADCmin of 779 × 10mm/s or lower were identified as being more likely to be associated with metastatic lesions. Significant differences in ADCmin and ADCmean were identified when comparing metastatic and non-metastatic SSTR-RADS-3B bone lesions (P < 0.05), with these parameters offering a high predictive ability (AUC = 0.94, AUC = 0.86).
CONCLUSION
Both diameter and ADCmin can aid in the accurate identification of the nature of lesions associated with SSTR-RADS-3A lymph nodes, whereas ADCmin and ADCmean values can inform the accurate interpretation of SSTR-RADS-3B bone lesions.
Topics: Humans; Neuroendocrine Tumors; Male; Female; Middle Aged; Organometallic Compounds; Aged; Retrospective Studies; Receptors, Somatostatin; Adult; Positron-Emission Tomography; Magnetic Resonance Imaging; Radiopharmaceuticals; Aged, 80 and over; Prognosis
PubMed: 38795250
DOI: 10.1007/s00432-024-05776-5 -
Pharmaceuticals (Basel, Switzerland) May 2024In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based...
Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer's, Anti-Inflammatory, and Cytotoxic Agents: Studies with Computational Predictions.
In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, -, -, and -, to evaluate their biological applications. The data from biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases -, -, and - showed that the six pyrazole-based Schiff bases , , , , , and possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases , , and are active against lung (A549) cells, while the two Schiff bases and exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases , , , , , and were evaluated. Furthermore, we assessed the absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.
PubMed: 38794225
DOI: 10.3390/ph17050655 -
Molecules (Basel, Switzerland) May 2024Recently, nanomaterials have attracted extensive attention in cancer-targeting therapy and as drug delivery vehicles owing to their unique surface and size properties....
Recently, nanomaterials have attracted extensive attention in cancer-targeting therapy and as drug delivery vehicles owing to their unique surface and size properties. Multifunctional combinations of nanomaterials have become a research hotspot as researchers aim to provide a full understanding of their nanomaterial characteristics. In this study, metal-organic framework-capped gold nanorod hybrids were synthesized. Our research explored their ability to kill tumor cells by locally increasing the temperature via photothermal conclusion. The specific peroxidase-like activity endows the hybrids with the ability to disrupt the oxidative balance in vitro. Simultaneously, chemotherapeutic drugs are administered and delivered by loading and transportation for effective combinatorial cancer treatment, thereby enhancing the curative effect and reducing the unpredictable toxicity and side effects of large doses of chemotherapeutic drugs. These studies can improve combinatorial cancer therapy and enhance cancer treatment.
Topics: Gold; Nanotubes; Metal-Organic Frameworks; Humans; Antineoplastic Agents; Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Metal Nanoparticles; Animals
PubMed: 38792244
DOI: 10.3390/molecules29102384 -
Molecules (Basel, Switzerland) May 2024The development of immobilized enzymes with high activity and stability is critical. Metal-organic frameworks (MOFs) have attracted much academic and industrial interest...
The development of immobilized enzymes with high activity and stability is critical. Metal-organic frameworks (MOFs) have attracted much academic and industrial interest in the field of enzyme immobilization due to their unique properties. In this study, the amino-functionalized ionic liquid (NIL)-modified metal-organic framework (UiO-66-NH) was prepared to immobilize lipase (CRL), using dialdehyde starch (DAS) as the cross-linker. The results of the Fourier transform infrared (FT-IR) spectra, X-ray powder diffraction (XRD), and scanning electronic microscopy (SEM) confirmed that the NIL was successfully grafted to UiO-66-NH. The CRL immobilized on NIL-modified UiO-66-NH (UiO-66-NH-NIL-DAS@CRL) exhibited satisfactory activity recovery (79.33%), stability, reusability, and excellent organic solvent tolerance. The research results indicated that ionic liquid-modified UiO-66-NH had practical potential for application in enzyme immobilization.
Topics: Lipase; Ionic Liquids; Enzymes, Immobilized; Metal-Organic Frameworks; Enzyme Stability; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Starch; Saccharomycetales; Phthalic Acids
PubMed: 38792242
DOI: 10.3390/molecules29102381 -
Molecules (Basel, Switzerland) May 2024With the rising incidence of various diseases in China and the constant development of the pharmaceutical industry, there is a growing demand for floxacin-type...
With the rising incidence of various diseases in China and the constant development of the pharmaceutical industry, there is a growing demand for floxacin-type antibiotics. Due to the large-scale production and high cost of waste treatment, the parent drug and its metabolites constantly enter the water environment through domestic sewage, production wastewater, and other pathways. In recent years, the pollution of the aquatic environment by floxacin has become increasingly serious, making the technology to degrade floxacin in the aquatic environment a research hotspot in the field of environmental science. Metal-organic frameworks (MOFs), as a new type of porous material, have attracted much attention in recent years. In this paper, four photocatalytic materials, MIL-53(Fe), NH-MIL-53(Fe), MIL-100(Fe), and g-CN, were synthesised and applied to the study of the removal of ofloxacin and enrofloxacin. Among them, the MIL-100(Fe) material exhibited the best photocatalytic effect. The degradation efficiency of ofloxacin reached 95.1% after 3 h under visible light, while enrofloxacin was basically completely degraded. The effects of different materials on the visible photocatalytic degradation of the floxacin were investigated. Furthermore, the photocatalytic mechanism of enrofloxacin and ofloxacin was revealed by the use of three trappers (▪O, h, and ▪OH), demonstrating that the role of ▪O promoted the degradation effect of the materials under photocatalysis.
Topics: Metal-Organic Frameworks; Catalysis; Quinolones; Water Pollutants, Chemical; Photolysis; Light; Ofloxacin; Photochemical Processes; Anti-Bacterial Agents; Enrofloxacin
PubMed: 38792155
DOI: 10.3390/molecules29102294