Search Results (62)

Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm² LED emitting at 660 nm with an energy of 15 J/cm². The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log₁₀ to 2 Log₁₀ CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log₁₀ to 6 Log₁₀ CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article

The hyperglycemic microenvironment in diabetic wounds predisposes them to bacterial infections, sustains chronic inflammation, and hinders therapeutic efficacy. In this study, antibiotic-loaded fast-crosslinked hybrid nanogel wound dressings (florfenicol nanogels) based on Schiff’s base bond were obtained through N, O-carboxymethyl chitosan (N, O-CMCS) and oxidized hyaluronic acid (OHA). The successfully prepared florfenicol N, O-CMCS/OHA nanogels exhibited obvious pH- and HAase-responsiveness release, which allowed it to quickly release florfenicol at infected wounds to exert on-demand antibacterial activity, as well as accelerate diabetic bacterial-infected wound healing. The nanogel dressings showed excellent antibacterial activity by destroying the bacterial cell membrane and wall. More specifically, the glucose oxidase in the dressings can catalyze the breakdown of high-concentration glucose, generating abundant ROS that directly cause cellular damage. According to the results of wound healing, the dressings showed satisfactory anti-inflammatory and therapeutic effects for the full-thickness mouse skin defect wounds. The nanogel dressings are anticipated to be excellent wound dressings to synergistically overcome the theraputic difficulty of diabetic bacterial wounds. Full article

Objectives: Jasminoidin (JA) and ursodeoxycholic acid (UA) have been shown to exert synergistic effects on cerebral ischemia (CI) therapy, but the underlying mechanisms remain to be elucidated. Objective: To elucidate the synergistic mechanisms involved in the combined use of JA and UA (JU) for CI therapy using a driver-induced modular screening (DiMS) strategy. Methods: Network proximity and topology-based approaches were used to identify synergistic modules and driver genes from an anti-ischemic microarray dataset (ArrayExpress, E-TABM-662). A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in 30 Sprague Dawley rats, divided into sham, vehicle, JA (25 mg/mL), UA (7 mg/mL), and JU (JA:UA = 1:1) groups. After 90 minutes of ischemia, infarct volume and neurological deficit scores were evaluated. Western blotting was performed 24 h after administration to validate key protein changes. Results: Six, eleven, and four drug-responsive On_modules were identified for JA, UA, and JU, respectively. Three synergistic modules (Sy-modules, JU-Mod-7, 8, and 10) and 12 driver genes (e.g., NRF1, FN1, CUL3) were identified, mainly involving the PI3K-Akt and MAPK pathways and regulation of the actin cytoskeleton. JA and UA synergistically reduced infarct volume and neurological deficit score (2.5, p < 0.05) in MCAO/R rats. In vivo studies demonstrated that JU suppressed the expression of CUL3, FN1, and ITGA4, while it increased that of NRF1. Conclusions: JU acts synergistically on CI–reperfusion injury by regulating FN1, CUL3, ITGA4, and NRF1 and inducing the PI3K-Akt, MAPK, and actin cytoskeleton pathways. DiMS provides a new approach to uncover mechanisms of combination therapies. Full article

This paper presents an optimized nonlinear controller, the Integral Super-Twisting Sliding Mode Control (ISTSMC), for acute leukemia therapy. To enhance its performance, we introduce the RedFox Optimization Algorithm, a nature-inspired technique based on the hunting behavior of red foxes. This algorithm is utilized to fine-tune the controller parameters, ensuring optimal achievement of control objectives. We discuss the fundamentals of ISTSMC, Sliding Mode Control, and Synergetic Control, detailing their optimization methodology using the RedFox Algorithm. The effectiveness of ISTSMC is evaluated through numerical simulations and compared with traditional Sliding Mode Control (SMC) and Synergetic Control (SC). The results demonstrate that ISTSMC achieves superior performance with a steady state error of 53.85, a settling time of 59.60, and a transient time of 4.7942, significantly outperforming SMC and SC. Additionally, ISTSMC reduces leukemic cell levels to a safe threshold more efficiently while maintaining healthy cell populations within acceptable limits. These improvements highlight the potential of ISTSMC in optimizing chemotherapy administration, ensuring better patient outcomes while minimizing side effects. Full article

Background: Recently proposed brain-tumor treatment strategies prioritize fast reduction of tumor cell population while often neglecting the radiation or chemotherapeutic drug dosage requirements to achieve it. Moreover, these techniques provide chemotherapy based treatment strategies, while ignoring the toxic side effects of the drugs employed by it. Methods: This study updates the recently proposed brain-tumor system dynamics by incorporating radiotherapy along with chemotherapy to simultaneously initiate both therapies for a more comprehensive and effective response against tumor proliferation. Afterwards, based on the upgraded system dynamics, this study proposes a novel multi-input sigmoid-based smooth synergetic nonlinear controller with the aim to reduce the dosage requirements of both therapies while keeping the overall system response robust and efficient. The novelty of this study lies in the combination of radiotherapy and chemotherapy inputs in a way that prioritizes patients health and well-being, while integrating advanced synergetic control technique with a sigmoid function based smoothing agent. Results: The proposed method reduced baseline radiation and chemo drug dosages by 57% and 33% respectively while effectively suppressing tumor growth and proliferation. Similarly, the proposed controller reduced the time required for complete tumor mitigation by 60% while reducing the radiation and chemotherapeutic drug intensity by 93.8% and 21.3% respectively. Conclusions: This study offers significant improvement in tumor treatment methodologies by providing a safer, less riskier brain-tumor treatment strategy that has promising potential to improve survival rates against this menacing health condition so that the affected patients may lead a healthier and better quality of life. Full article

Metal–organic frameworks (MOFs) are a class of inorganic-organic hybrid nanoparticles formed by the coordination of metal ions/clusters and organic ligands. Due to their high porosities, large surface areas, adjustable structures, and responsiveness to light/sound, etc., MOFs have shown great clinical potential in the field of tumor therapy. Tumor immunotherapy exerts antitumor effects through reshaping tumor immune microenvironment, showing significant preclinical and clinical advantages. Based on the mechanisms of immunity activation, the tumor immunotherapy agents can be divided into chemotherapeutic agents, immunomodulators, enzymes, tumor vaccines and oligonucleotide drugs, etc. Herein, we review the MOFs-based drug delivery systems for tumor immunotherapy. The classification of MOFs, followed by their antitumor immunity activation mechanisms, are first introduced. Drug delivery systems based on MOFs with different immunotherapy agents are also summarized, especially the synergetic immunity activation mechanisms triggered by MOFs and their loadings. Furthermore, the merits and drawbacks of MOFs and the potential strategies for MOFs to promote their clinical applications are discussed. Full article

Background/Objectives: With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS levels and drugs that inhibit antioxidant programs. Methods: Considering that dihydroartemisinin (DHA) can cause oxidative damage to protein, DNA, or lipids by producing excessive ROS, while, disulfiram (DSF) can inhibit glutathione (GSH) levels and achieve the therapeutic effect by inhibiting antioxidant system and amplifying oxidative stress, they were co-loaded onto the copper peroxide nanoparticles (CuO₂) coated with copper tannic acid (Cu-TA), to build a drug delivery system of CuO₂@Cu-TA@DSF/DHA nanoparticles (CCTDD NPs). In response to the tumor microenvironment, DHA interacts with copper ion (Cu²⁺) to produce ROS, and a double (diethylthiocarbamate)-copper (II) (CuET) is generated by the complexation of DSF and Cu²⁺, which consumes GSH and inhibits antioxidant system. Meanwhile, utilizing the Fenton-like effect induced by the multi-copper mode can achieve ROS storm, activate the MAPK pathway, and achieve chemotherapy (CT) and chemodynamic (CDT). Results: Taking pancreatic cancer cell lines PANC-1 and BxPC-3 as the research objects, cell line experiments in vitro proved that CCTDD NPs exhibit efficient cytotoxicity on cancer cells. Conclusions: The CCTDD NPs show great potential in resisting pancreatic cancer cells and provides a simple strategy for designing powerful metal matrix composites. Full article

The combination of paclitaxel (PTX) with other chemotherapy drugs (e.g., gemcitabine, GEM) or genetic drugs (e.g., siRNA) has been shown to enhance therapeutic efficacy against tumors, reduce individual drug dosages, and prevent drug resistance associated with single-drug treatments. However, the varying solubility of chemotherapy drugs and genetic drugs presents a challenge in co-delivering these agents. In this study, nanoparticles loaded with PTX were prepared using the biodegradable polymer material poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). These nanoparticles were surface-modified with target proteins (Affibody molecules) and RALA cationic peptides to create core-shell structured microspheres with targeted and cationic functionalization. A three-drug co-delivery system (PTX@PHBHHx-ARP/siRNA_GEM) were developed by electrostatically adsorbing siRNA chains containing GEM onto the microsphere surface. The encapsulation efficiency of PTX in the nanodrug was found to be 81.02%, with a drug loading of 5.09%. The chemogene adsorption capacity of siRNA_GEM was determined to be 97.3%. Morphological and size characterization of the nanodrug revealed that PTX@PHBHHx-ARP/siRNA_GEM is a rough-surfaced microsphere with a particle size of approximately 150 nm. This nanodrug exhibited targeting capabilities toward BT474 cells with HER2 overexpression while showing limited targeting ability toward MCF-7 cells with low HER2 expression. Results from the MTT assay demonstrated that PTX@PHBHHx-ARP/siRNA_GEM exhibits high cytotoxicity and excellent combination therapy efficacy compared to physically mixed PTX/GEM/siRNA. Additionally, Western blot analysis confirmed that siRNA-mediated reduction of Bcl-2 expression significantly enhanced cell apoptosis mediated by PTX or GEM in tumor cells, thereby increasing cell sensitivity to PTX and GEM. This study presents a novel targeted nanosystem for the co-delivery of chemotherapy drugs and genetic drugs. Full article

The synergetic strategy has created tremendous advantages in drug-resistance bacterial infection treatment, whereas challenges related to novel compound discovery and identifying drug-binding targets still remain. The mechanisms of antimicrobial resistance involving β-lactamase catalysis and the degradation of β-lactam antibiotics are being revealed, with relevant therapies promising to improve the efficacy of existing major classes of antibiotics in the foreseeable future. In this study, it is demonstrated that nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, efficiently potentiated the activities of β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by suppressing β-lactamase performance and improving the bacterial biofilm susceptibility to antibiotics. Nordalbergin was found to destabilize the cell membrane and promote its permeabilization. Moreover, nordalbergin efficiently improved the therapeutic efficacy of amoxicillin against MRSA pneumonia in mice, as supported by the lower bacterial load, attenuated pathological damage, and decreased inflammation level. These results demonstrate that nordalbergin might be a promising synergist of amoxicillin against MRSA infections. This study provided a new approach for developing potentiators for β-lactam antibiotics against MRSA infections. Full article

Small interfering RNA (siRNA) has significant potential as a treatment for cancer by targeting specific genes or molecular pathways involved in cancer development and progression. The addition of siRNA to other therapeutic strategies, like photodynamic therapy (PDT), can enhance the anticancer effects, providing synergistic benefits. Nevertheless, the effective delivery of siRNA into target cells remains an obstacle in cancer therapy. Herein, supramolecular nanoparticles were fabricated via the co-assembly of natural histone and hyaluronic acid for the co-delivery of HMGB1-siRNA and the photosensitizer chlorin e6 (Ce6) into the MCF-7 cell. The produced siRNA-Ce6 nanoparticles (siRNA-Ce6 NPs) have a spherical morphology and exhibit uniform distribution. In vitro experiments demonstrate that the siRNA-Ce6 NPs display good biocompatibility, enhanced cellular uptake, and improved cytotoxicity. These outcomes indicate that the nanoparticles constructed by the co-assembly of histone and hyaluronic acid hold enormous promise as a means of siRNA and photosensitizer co-delivery towards synergetic therapy. Full article

Nanomaterials, with unique physical, chemical, and biocompatible properties, have attracted significant attention as an emerging active platform in cancer diagnosis and treatment. Amongst them, metal–organic framework (MOF) nanostructures are particularly promising as a nanomedicine due to their exceptional surface functionalities, adsorption properties, and organo-inorganic hybrid characteristics. Furthermore, when bioactive substances are integrated into the structure of MOFs, these materials can be used as anti-tumor agents with superior performance compared to traditional nanomaterials. In this review, we highlight the most recent advances in MOFs-based materials for tumor therapy, including their application in cancer treatment and the underlying mechanisms. Full article

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation. Full article

In the treatment of various cancers, photodynamic therapy (PDT) has been extensively studied as an effective therapeutic modality. As a potential alternative to conventional chemotherapy, PDT has been limited due to the low Reactive Oxygen Species (ROS) yield of photosensitisers. Herein, a nanoplatform containing mesoporous Fe₃O₄@TiO₂ microspheres was developed for near-infrared (NIR)-light-enhanced chemodynamical therapy (CDT) and PDT. Titanium dioxide (TiO₂) has been shown to be a very effective PDT agent; however, the hypoxic tumour microenvironment partly affects its in vivo PDT efficacy. A peroxidase-like enzyme, Fe₃O₄, catalyses the decomposition of H₂O₂ in the cytoplasm to produce O₂, helping overcome tumour hypoxia and increase ROS production in response to PDT. Moreover, Fe²⁺ in Fe₃O₄ could catalyse H₂O₂ decomposition to produce cytotoxic hydroxyl radicals within tumour cells, which would result in tumour CDT. The photonic hyperthermia of Fe₃O₄@TiO₂ could not only directly damage the tumour but also improve the efficiency of CDT from Fe₃O₄. Cancer-killing effectiveness has been maximised by successfully loading the chemotherapeutic drug DOX, which can be released efficiently using NIR excitation and slight acidification. Moreover, the nanoplatform has high saturation magnetisation (20 emu/g), making it suitable for magnetic targeting. The in vitro results show that the Fe₃O₄@TiO₂/DOX nanoplatforms exhibited good biocompatibility as well as synergetic effects against tumours in combination with CDT/PDT/PTT/chemotherapy. Full article

Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases. Full article

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5–10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues. Full article