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Heliyon May 2024Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints of the human body and is projected to have a prevalence age-standardized... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints of the human body and is projected to have a prevalence age-standardized rate of 1.5 million new cases worldwide by 2030. Several conventional and non-conventional preventive and therapeutic interventions have been suggested but they have their side effects including nausea, abdominal pain, liver damage, ulcers, heightened blood pressure, coagulation, and bleeding. Interestingly, several food-derived peptides (FDPs) from both plant and animal sources are increasingly gaining a reputation for their potential in the management or therapy of RA with little or no side effects. In this review, the concept of inflammation, its major types (acute and chronic), and RA identified as a chronic type were discussed based on its pathogenesis and pathophysiology. The conventional treatment options for RA were briefly outlined as the backdrop of introducing the FDPs that potentiate therapeutic effects in the management of RA.
PubMed: 38778960
DOI: 10.1016/j.heliyon.2024.e31104 -
Frontiers in Oncology 2022Anti-angiogenesis therapy and immunotherapy are the first-line therapeutic strategies for various tumor treatments in the clinic, bringing significant advantages for... (Review)
Review
Anti-angiogenesis therapy and immunotherapy are the first-line therapeutic strategies for various tumor treatments in the clinic, bringing significant advantages for tumor patients. Recent studies have shown that anti-angiogenic therapy can potentiate immunotherapy, with many clinical trials conducted based on the combination of anti-angiogenic agents and immune checkpoint inhibitors (ICIs). However, currently available clinical dosing strategies and tools are limited, emphasizing the need for more improvements. Although significant progress has been achieved, several big questions remained, such as how to achieve cell-specific targeting in the tumor microenvironment? How to improve drug delivery efficiency in tumors? Can nanotechnology be used to potentiate existing clinical drugs and achieve synergistic sensitization effects? Over the recent few years, nanomedicines have shown unique advantages in antitumor research, including cell-specific targeting, improved delivery potentiation, and photothermal effects. Given that the applications of nanomaterials in tumor immunotherapy have been widely reported, this review provides a comprehensive overview of research advances on nanomaterials in anti-angiogenesis therapy, mainly focusing on the immunosuppressive effects of abnormal tumor vessels in the tumor immune microenvironment, the targets and strategies of anti-angiogenesis nanomedicines, and the potential synergistic effects and molecular mechanisms of anti-angiogenic nanomedicines in combination with immunotherapy, ultimately providing new perspectives on the nanomedicine-based synergy between anti-angiogenic and immunotherapy.
PubMed: 36523993
DOI: 10.3389/fonc.2022.1039378 -
Frontiers in Microbiology 2022Antimicrobial resistance in clinically important microbes has emerged as an unmet challenge in global health. Extensively drug-resistant bacterial pathogens have cropped... (Review)
Review
Antimicrobial resistance in clinically important microbes has emerged as an unmet challenge in global health. Extensively drug-resistant bacterial pathogens have cropped up lately defying the action of even the last resort of antibiotics. This has led to a huge burden in the health sectors and increased morbidity and mortality rate across the world. The dwindling antibiotic discovery pipeline and rampant usage of antibiotics has set the alarming bells necessitating immediate actions to combat this looming threat. Various alternatives to discovery of new antibiotics are gaining attention such as reversing the antibiotic resistance and hence reviving the arsenal of antibiotics in hand. Antibiotic resistance reversal is mainly targeted against the antibiotic resistance mechanisms, which potentiates the effective action of the antibiotic. Such compounds are referred to as resistance breakers or antibiotic adjuvants/potentiators that work in conjunction with antibiotics. Many studies have been conducted for the identification of compounds, which decrease the permeability barrier, expression of efflux pumps and the resistance encoding enzymes. Compounds targeting the stability, inheritance and dissemination of the mobile genetic elements linked with the resistance genes are also potential candidates to curb antibiotic resistance. In pursuit of such compounds various natural sources and synthetic compounds have been harnessed. The activities of a considerable number of compounds seem promising and are currently at various phases of clinical trials. This review recapitulates all the studies pertaining to the use of antibiotic potentiators for the reversal of antibiotic resistance and what the future beholds for their usage in clinical settings.
PubMed: 35847117
DOI: 10.3389/fmicb.2022.887251 -
Frontiers in Cellular Neuroscience 2022Although lithium has long been one of the most widely used pharmacological agents in psychiatry, its mechanisms of action at the cellular and molecular levels remain...
Although lithium has long been one of the most widely used pharmacological agents in psychiatry, its mechanisms of action at the cellular and molecular levels remain poorly understood. One of the targets of Li is the phosphoinositide pathway, but whereas the impact of Li on inositol lipid metabolism is well documented, information on physiological effects at the cellular level is lacking. We examined in two mammalian cell lines the effect of acute Li exposure on the mobilization of internal Ca and phospholipase C (PLC)-dependent membrane conductances. We first corroborated by Western blots and immunofluorescence in HEK293 cells the presence of key signaling elements of a muscarinic PLC pathway (M1AchR, G, PLC-β1, and IPRs). Stimulation with carbachol evoked a dose-dependent mobilization of Ca, as determined with fluorescent indicators. This was due to release from internal stores and proved susceptible to the PLC antagonist U73122. Li exposure reproducibly potentiated the Ca response in a concentration-dependent manner extending to the low millimolar range. To broaden those observations to a neuronal context and probe potential Li modulation of electrical signaling, we next examined the cell line SHsy5y. We replicated the potentiating effects of Li on the mobilization of internal Ca, and, after characterizing the basic properties of the electrical response to cholinergic stimulation, we also demonstrated an equally robust upregulation of muscarinic membrane currents. Finally, by directly stimulating the signaling pathway at different links downstream of the receptor, the site of action of the observed Li effects could be narrowed down to the G protein and its interaction with PLC-β. These observations document a modulation of G/PLC/IP-mediated signaling by acute exposure to lithium, reflected in distinct physiological changes in cellular responses.
PubMed: 35242014
DOI: 10.3389/fncel.2022.838939 -
Science Advances Feb 2024Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly...
Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly understood. Gamma oscillations (30 to 80 hertz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma power. Gamma potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit computational model of CA3 gamma oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma power and completely accounts for gamma potentiation. We reaffirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma potentiation requires PVI-specific signaling via a Gq/PKC pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma activity-dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.
Topics: Animals; Parvalbumins; Hippocampus; Long-Term Potentiation; Signal Transduction; Interneurons; Neuronal Plasticity
PubMed: 38295164
DOI: 10.1126/sciadv.adj7427 -
Radiology and Oncology Mar 2022One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates the entry of...
BACKGROUND
One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice.
MATERIALS AND METHODS
The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.
RESULTS
The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treatment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the highest used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism.
CONCLUSIONS
ECT and sunitinib combined treatment has clinical potential, and further studies are warranted.
Topics: Antineoplastic Agents; Bleomycin; Electrochemotherapy; Humans; Pancreatic Neoplasms; Sunitinib
PubMed: 35344644
DOI: 10.2478/raon-2022-0009 -
Molecules (Basel, Switzerland) Oct 2019Surface disinfection is of utmost importance in the prevention of bacterial infections. This study aims to assess the ability of ten phytochemicals and related...
Surface disinfection is of utmost importance in the prevention of bacterial infections. This study aims to assess the ability of ten phytochemicals and related derivatives as potentiators of two commonly used biocides-cetyltrimethylammonium bromide (CTAB) and lactic acid (LA). LA in combination with cinnamic, hydrocinnamic, α-methylcinnamic, and α-fluorocinnamic acids had a factional inhibitory concentration index (FICI) ≤ 1 for and . Several phytochemicals/derivatives in combination with biocides improved the biocidal efficacy against early sessile bacteria. The most effective combination was LA with allyl cinnamate (2.98 ± 0.76 log CFU.cm reduction) against . The combination with CTAB was successful for most phytochemicals/derivatives with a maximum bactericidal efficacy against sessile when combined with allyl cinnamate (2.20 ± 0.07 log CFU.cm reduction) and for when combined with α-methylcinnamic acid (1.68 ± 0.30 log CFU.cm reduction). This study highlights the potential of phytochemicals and their derivatives to be used in biocide formulations.
Topics: Bacteria; Cetrimonium; Cinnamates; Disinfectants; Hydrophobic and Hydrophilic Interactions; Lactic Acid; Microbial Sensitivity Tests; Phytochemicals
PubMed: 31671687
DOI: 10.3390/molecules24213918 -
International Journal of Molecular... Aug 2022Cell-cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the... (Review)
Review
Cell-cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the mechanism of gap junction channel gating by anesthetics is still poorly understood. In the early nineties, we reported that gating by anesthetics is strongly potentiated by caffeine and theophylline and inhibited by 4-Aminopyridine. Neither Ca channel blockers nor 3-isobutyl-1-methylxanthine (IBMX), forskolin, CPT-cAMP, 8Br-cGMP, adenosine, phorbol ester or H7 had significant effects on gating by anesthetics. In our publication, we concluded that neither cytosolic Ca nor pH were involved, and suggested a direct effect of anesthetics on gap junction channel proteins. However, while a direct effect cannot be excluded, based on the potentiating effect of caffeine and theophylline added to anesthetics and data published over the past three decades, we are now reconsidering our earlier interpretation and propose an alternative hypothesis that uncoupling by heptanol, halothane and isoflurane may actually result from a rise in cytosolic Ca concentration ([Ca]) and consequential activation of calmodulin linked to gap junction proteins.
Topics: Anesthetics; Anesthetics, Inhalation; Caffeine; Calcium; Calmodulin; Cell Communication; Connexins; Gap Junctions; Halothane; Heptanol; Ion Channels; Isoflurane; Theophylline
PubMed: 36012286
DOI: 10.3390/ijms23169017 -
Frontiers in Microbiology 2023
PubMed: 36960280
DOI: 10.3389/fmicb.2023.1173906 -
Plants (Basel, Switzerland) May 2022The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been...
The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.
PubMed: 35684161
DOI: 10.3390/plants11111388