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Topic Review
Matrix Metalloproteinases
Matrix metalloproteinases (MMPs) are zinc-dependent proteases that have been extensively studied in the context of extracellular matrix (ECM) breakdown and remodelling.
  • 667
  • 18 Mar 2021
Topic Review
Mechanism of Adjuvanticity
Vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of one or more adjuvants represents the key to enhance the response of the immune signal to the antigen, thus accelerating and increasing the duration and the potency of the protective effect. Their use is of particular importance for vulnerable populations, such as the elderly or immunocompromised people.
  • 462
  • 01 Jun 2023
Topic Review
Mechanism of Antibiotics Resistance
Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and discharging antibiotics out of cells through an efflux pump, etc. Bacteria are found to constantly evolve new resistance mechanisms to antibiotics, including target protective protein, changes in cell morphology, and so on, endowing them with multiple defense systems against antibiotics, leading to the emergence of multi-drug resistant (MDR) bacteria and the unavailability of drugs in clinics. 
  • 1.0K
  • 28 Sep 2022
Topic Review
Mechanisms of anticoagulant drugs
Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis. In case of older anticoagulant drugs like heparin and warfarin, dose adjustment is required owing to narrow therapeutic ranges. The established monitoring methods for heparin and warfarin are activated partial thromboplastin time (APTT)/anti-Xa assay and prothrombin time – international normalized ratio (PT-INR), respectively. Since 2008, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), have been widely prescribed to prevent and treat several thromboembolic diseases. Although the use of DOACs without routine monitoring and frequent dose adjustment has been shown to be safe and effective, there may be clinical circumstances in specific patients when measurement of the anticoagulant effects of DOACs is required. Recently, anticoagulation therapy has received attention when treating patients with coronavirus disease 2019 (COVID-19).
  • 8.8K
  • 23 Feb 2023
Topic Review
Mechanisms of CYP450 Inhibition
In an ageing society, polypharmacy has become a major public health and economic issue. Overuse of medications, especially in patients with chronic diseases, carries major health risks. One common consequence of polypharmacy is the increased emergence of adverse drug events, mainly from drug–drug interactions. The majority of currently available drugs are metabolized by CYP450 enzymes. Interactions due to shared CYP450-mediated metabolic pathways for two or more drugs are frequent, especially through reversible or irreversible CYP450 inhibition. The magnitude of these interactions depends on several factors, including varying affinity and concentration of substrates, time delay between the administration of the drugs, and mechanisms of CYP450 inhibition. Various types of CYP450 inhibition (competitive, non-competitive, mechanism-based) have been observed clinically, and interactions of these types require a distinct clinical management strategy.
  • 1.5K
  • 17 May 2021
Topic Review
Mechanisms of Light-Triggered Drug Release from Liposomes
Light-triggered mechanisms that can be exploited to release encapsulated drugs from liposomes are photoisomerization, photocleavage (photo-oxidation), surface plasmon resonance absorption (photothermal activation), photochemical hydrophobicity change (photochemical activation), and photo-crosslinking and de-crosslinking.
  • 305
  • 18 Feb 2024
Topic Review
Mechanisms of Neurorespiratory Toxicity Induced by Fentanyl Analogs
In 2020, fentanyl and its analogs contributed to ~65% of drug-attributed fatalities in the USA, with a threatening increasing trend during the last ten years. These synthetic opioids used as potent analgesics in human and veterinary medicine have been diverted to recreational aims, illegally produced and sold. Like all opioids, central nervous system depression resulting from overdose or misuse of fentanyl analogs is characterized clinically by the onset of consciousness impairment, pinpoint miosis and bradypnea. However, contrasting with what observed with most opioids, thoracic rigidity may occur rapidly with fentanyl analogs, contributing to increasing the risk of death in the absence of immediate life support. Various mechanisms have been proposed to explain this particularity associated with fentanyl analogs, including the activation of noradrenergic and glutamatergic coerulospinal neurons and dopaminergic basal ganglia neurons. Due to the high affinities to the mu-opioid receptor, the need for more elevated naloxone doses than usually required in morphine overdose to reverse the neurorespiratory depression induced by fentanyl analogs has been questioned. 
  • 326
  • 03 May 2023
Topic Review
Mechanisms of Resistance to Gemcitabine
Gemcitabine is still the standard-of-care chemotherapeutic drug for pancreatic ductal adenocarcinoma (PDAC). However, the response rate is quite low. There are multiple mechanisms and participants in gemcitabine resistance.
  • 855
  • 01 Jun 2022
Topic Review
Mechanistically Coupled PK (MCPK) Model of Dabrafenib Metabolism
Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and consequential relapse. A clinical drug-dose determination study shows increased pERK levels upon daily administration of more than 300 mg dabrafenib. To clarify whether such elevated drug concentrations could be reached by long-term drug accumulation, the pharmacokinetics (MCPK) of dabrafenib and its metabolites were mechanistically coupled. The MCPK model is qualitatively based on in vitro and quantitatively on clinical data to describe occupancy-dependent CYP3A4 enzyme induction, accumulation, and drug–drug interaction mechanisms. The prediction suggests an eight-fold increase in the steady-state concentration of potent desmethyl-dabrafenib and its inactive precursor carboxy-dabrafenib within four weeks upon 150 mg b.d. dabrafenib. While it is generally assumed that a higher dose is not critical, it was found experimentally that a high physiological dabrafenib concentration fails to induce cell death in embedded 451LU melanoma spheroids.
  • 383
  • 29 Jan 2022
Topic Review
Medical and Non-Medical USA Opioid Crisis
Drug overdose deaths in the USA rose from 16,849 in 1999 to nearly 110,000—of which an estimated 75,000 involved opioids—in 2022. On a yearly basis, the opioid casualty rate is higher than the combined number of victims of firearm violence and car accidents. The COVID-19 epidemic might have helped to worsen the addiction crisis in the USA by stimulating drug use among adolescents and diverting national attention to yet another public health crisis. So far, the failure to effectively respond to the opioid crisis is due to the gap between narcotic product regulation, regulation of marketing practices and the rise of a corporate-dominated health care system. 
  • 122
  • 12 Nov 2023
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