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Topic Review
Molecular Mechanisms of Colistin Resistance in Acinetobacter baumannii
Colistin, as a positively charged peptide, exerts its antibacterial effect via electrostatic interactions with negatively charged lipid A, a component of lipopolysaccharide (LPS). Accordingly, two main mechanisms of colistin resistance have been described in Acinetobacter baumannii (A. baumannii): the complete loss or modifications of the target LPS, leading to abolishing or reducing its negative charge. The complete loss of LPS results from inactivation of the first three genes of the lipid A biosynthetic pathway (lpxA, lpxC, and lpxD genes), whereas the modification of LPS occurs through the addition of phosphoethanolamine (PEtN) moieties to lipid A by the pmrCAB operon-encoded enzymes. Although 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification of LPS has been described as a more common and effective colistin resistance mechanism compared to PEtN LPS modification in diverse Gram-negative pathogens (Salmonella enterica, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa), it was absent in A. baumannii. In addition to chromosome-mediated mechanisms, plasmid-mediated colistin resistance encoded by mcr genes has been recognized as a major driver of rapid dissemination by horizontal gene transfer among pathogenic Gram-negative bacteria, including A. baumannii.
  • 1.4K
  • 21 Mar 2023
Topic Review
Antimicrobial Peptides and Antibiotics
Antimicrobial peptides constitute one of the most promising alternatives to antibiotics since they could be used to treat bacterial infections, especially those caused by multidrug-resistant pathogens. Many antimicrobial peptides, with various activity spectra and mechanisms of actions, have been described. 
  • 1.4K
  • 23 Sep 2021
Topic Review
ADAM 17 and Epithelial-to-Mesenchymal Transition
For decades, metalloproteinase 17 (ADAM17) has been the goal of wide investigation. Since its discovery as the tumour necrosis factor-α convertase, it has been studied as the main drug target, especially in the context of inflammatory conditions and tumour. In fact, evidence is mounting to support a key role of ADAM17 in the induction of the proliferation, migration and progression of tumour cells and the trigger of the pro-fibrotic process during chronic inflammatory conditions; this occurs, probably, through the activation of epithelial-to-mesenchymal transition (EMT). EMT is a central morphologic conversion that occurs in adults during wound healing, tumour progression and organ fibrosis. EMT is characterised by the disassembly of cell–cell contacts, remodelling of the actin cytoskeleton and separation of cells, and generates fibroblast-like cells that express mesenchymal markers and have migratory properties. This transition is characterised by loss of epithelial proteins such as E-cadherin and the acquisition of new mesenchymal markers, including vimentin and a-smooth muscle actin.
  • 1.4K
  • 03 Aug 2021
Topic Review
Nox4
The NADPH oxidase Nox4 is a hydrogen peroxide (H2O2)-producing enzyme, with the highest expression in the kidney. As the kidney is involved in volume and blood pressure control through sodium handling, we set out to determine the impact of a low sodium diet on these parameters in WT and Nox4-/- mice. Nox4 expression in the murine kidney was restricted to the proximal tubule. Nevertheless, low-sodium-induced weight loss and sodium sparing function was similar in WT and Nox4-/- mice, disputing an important function of renal Nox4 in sodium handling. In contrast, a low sodium diet resulted in a reduction in systolic blood pressure in Nox4-/- as compared to WT mice. This was associated with a selectively lower pressure to heart-rate ratio, as well as heart to body weight ratio. In general, a low sodium diet leads to activation of sympathetic tone and the renin angiotensin system, which subsequently increases peripheral resistance. Our observations suggest that the control by this system is attenuated in Nox4-/- mice, resulting in lower blood pressure in response to low sodium.
  • 1.4K
  • 24 Aug 2021
Topic Review
Hypoxia (Medical)
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during hypoventilation training or strenuous physical exercise. Hypoxia differs from hypoxemia and anoxemia in that hypoxia refers to a state in which oxygen supply is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or zero arterial oxygen supply. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia. Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness leading to potentially fatal complications: high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, e.g. while diving underwater especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. Mild, non-damaging intermittent hypoxia is used intentionally during altitude training to develop an athletic performance adaptation at both the systemic and cellular level. In acute or silent hypoxia, a person's oxygen level in blood cells and tissue can drop without any initial warning, even though the individual's chest x-ray shows diffuse pneumonia with an oxygen level below normal. Doctors report cases of silent hypoxia with COVID-19 patients who did not experience shortness of breath or coughing until their oxygen levels had plummeted to such a degree that the patients risked acute respiratory distress (ARDS) and organ failure. In a The New York Times opinion piece (April 20, 2020), emergency room doctor Richard Levitan reports: "A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage—seemingly incompatible with life—but they were using their cellphones as we put them on monitors." Hypoxia is a common complication of preterm birth in newborn infants. Because the lungs develop late in pregnancy, premature infants frequently possess underdeveloped lungs. To improve lung function, doctors frequently place infants at risk of hypoxia inside incubators (also known as humidicribs) that provide warmth, humidity, and oxygen. More serious cases are treated with CPAP. The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza in recognition of their discovery of cellular mechanisms to sense and adapt to different oxygen concentrations, establishing a basis for how oxygen levels affect physiological function.
  • 1.4K
  • 01 Dec 2022
Topic Review
Rare Genetic Syndromes and Oral Anomalies
Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district.
  • 1.4K
  • 10 Jan 2022
Topic Review
Gut–Lung Axis Communication in COVID-19
The ecosystem of the human gastrointestinal tract, named gut microbiota, represents the most thoroughly mapped ecosystem. Perturbations on bacterial populations cause dysbiosis, a condition correlated to a wide range of autoimmune, neurological, metabolic, cardiovascular, and respiratory diseases. The lungs have their flora, which are directly related to the gut flora via bidirectional communication allowing the transport of microbial metabolites and toxins produced by intestinal bacteria through the circulation and lymphatic system. This mutual microbial cross-talk communication called the gut–lung axis modulates the immune and inflammatory response to infections. COVID-19 causes dysbiosis, altered intestinal permeability, and bacterial translocation. Dysbiosis, through the gut–lung axis, promotes hyper-inflammation, exacerbates lung damage, and worsens clinical outcomes.
  • 1.4K
  • 08 Sep 2022
Topic Review
Heat Therapy
Heat therapy, also called thermotherapy, is the use of heat in therapy, such as for pain relief and health. It can take the form of a hot cloth, hot water bottle, ultrasound, heating pad, hydrocollator packs, whirlpool baths, cordless FIR heat therapy wraps, and others. It can be beneficial to those with arthritis and stiff muscles and injuries to the deep tissue of the skin. Heat may be an effective self-care treatment for conditions like rheumatoid arthritis. Heat therapy is most commonly used for rehabilitation purposes. The therapeutic effects of heat include increasing the extensibility of collagen tissues; decreasing joint stiffness; reducing pain; relieving muscle spasms; reducing inflammation, edema, and aids in the post acute phase of healing; and increasing blood flow. The increased blood flow to the affected area provides proteins, nutrients, and oxygen for better healing.
  • 1.4K
  • 31 Oct 2022
Topic Review
Taurine in Mitochondria Health
Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was first approved as the treatment among heart failure patients in Japan. Accumulating studies have shown that taurine supplementation also protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders.
  • 1.4K
  • 17 Aug 2021
Topic Review
Angiogenic Switch
Regular physical activity in cyclic sports can influence the so-called “angiogenic switch”, which is considered as an imbalance between proangiogenic and anti-angiogenic molecules. Disruption of the synthesis of angiogenic molecules can be caused by local changes in tissues under the influence of excessive physical exertion and its consequences, such as chronic oxidative stress and associated hypoxia, metabolic acidosis, sports injuries, etc. 
  • 1.4K
  • 22 Jul 2021
Topic Review
CD123
The interleukin-3 receptor alpha chain (IL-3R), more commonly referred to as CD123, is widely overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin lymphoma and particularly, blastic plasmacytoid dendritic neoplasm (BPDCN). Importantly, CD123 is expressed at both the level of leukemic stem cells (LSCs) and more differentiated leukemic blasts, which makes CD123 an attractive therapeutic target. Various agents have been developed as drugs able to target CD123 on malignant leukemic cells and on the normal counterpart. Tagraxofusp (SL401, Stemline Therapeutics), a recombinant protein composed of a truncated diphtheria toxin payload fused to IL-3, was approved for use in patients with BPDCN in December of 2018 and showed some clinical activity in AML. Different monoclonal antibodies directed against CD123 are under evaluation as antileukemic drugs, showing promising results either for the treatment of AML minimal residual disease or of relapsing/refractory AML or BPDCN. 
  • 1.4K
  • 13 Sep 2021
Topic Review
Chest Drainage Management
Chest drains are used to preserve respiratory function and haemodynamic stability. One can also utilize a flutter valve, but these do not enable application of negative pressure. The generation of an active sub-atmospheric pressure or vacuum builds the basis of chest drain management. A vacuum is defined as “space with zero pressure” generating a difference in pressure between the pleural space and the atmosphere creates sub-atmospheric pressure in the pleural space, which is used to generate a vacuum in the chest drains.
  • 1.4K
  • 28 Oct 2022
Topic Review
Estrogen Sulfotransferase
Estrogen sulfotransferase (SULT1E1) is a phase II enzyme that sulfates estrogens to inactivate them and regulate their homeostasis. This enzyme is also involved in the sulfation of thyroid hormones and several marketed medicines. Though the profound action of SULT1E1 in molecular/pathological biology has been extensively studied, its genetic variants and functional studies have been comparatively rarely studied. 
  • 1.4K
  • 06 Jul 2021
Topic Review
Liver Diseases and Nutritional Status
Liver fibrosis is the consequence of different inflammatory processes occurring in any chronic liver disease. Its progression determines the development of cirrhosis and portal hypertension. The natural history of cirrhosis is characterized by a compensated phase, with or without portal hypertension, and a decompensated phase characterized by the appearance of major complications, such as ascites, portal hypertensive bleeding, encephalopathy, and jaundice. Malnutrition is frequent in patients with liver cirrhosis, which progresses in parallel with the worsening of the disease. Its etiology is multifactorial, given the great impact of liver disease on multiple processes related to nutrition.
  • 1.4K
  • 27 May 2021
Topic Review
The Effects of Collagen Treatment in Clinical Studies
Collagen is a good treatment candidate for OA among the different therapeutic options due to its safety and clinical evidence. Two different approaches for collagen include collagen hydrolysates and native collagen and both types of collagen nutraceuticals are effective in reducing OA pain, in animal models and human clinical trials. Native collagen, which may be poorly absorbed, could work through a mechanism of oral induction, and hydrolyzed collagen can reach the target site where collagen synthesis is needed.
  • 1.4K
  • 17 Nov 2021
Topic Review
Mechanical Heart Valve Patients with Intracranial Hemorrhage
The management of an intracranial hemorrhage in patients receiving anticoagulant therapy presents a significant challenge for medical professionals. Anticoagulant treatment is intended to prevent blood clotting, but it can worsen active brain bleeds. Despite this risk, avoiding the prothrombotic state caused by mechanical heart valves remains crucial. 
  • 1.4K
  • 17 May 2023
Topic Review
LEAP Motion Technology and Psychology
Technological advancement is constantly evolving, and it is also developing in the mental health field. Various applications, often based on virtual reality, have been implemented to carry out psychological assessments and interventions, using innovative human–machine interaction systems. In this context, the LEAP Motion sensing technology has raised interest, since it allows for more natural interactions with digital contents, via an optical tracking of hand and finger movements. 
  • 1.4K
  • 14 Sep 2021
Topic Review
Herbal Biomedicines for Dermatological Disorders
Herbal extracts and isolated plant compounds play an increasing role in the treatment of skin disorders and wounds. Several new herbal drugs, medicinal products and cosmetic products for the treatment of various skin conditions have been developed in recent years. 
  • 1.4K
  • 01 Jul 2021
Topic Review
Pathophysiology of Chronic Constipation
Constipation is one of the major gastrointestinal disorders diagnosed in clinical practice in Western countries. Almost 20% of population suffer from this disorder, which means constipation is a substantial utilization of healthcare. Pathophysiology of constipation is complex and multifactorial, where aspects like disturbance in colonic transit, genetic predisposition, lifestyle habits, psychological distress, and many others need to be taken into consideration.
  • 1.4K
  • 25 Apr 2021
Topic Review
CD147
Microenvironment plays a crucial role in tumor development and progression. Cancer cells modulate the tumor microenvironment, which also contribute to resistance to therapy. Identifying biomarkers involved in tumorigenesis and cancer progression represents a great challenge for cancer diagnosis and therapeutic strategy development. CD147 is a glycoprotein involved in the regulation of the tumor microenvironment and cancer progression by several mechanisms—in particular, by the control of glycolysis and also by its well-known ability to induce proteinases leading to matrix degradation, tumor cell invasion, metastasis and angiogenesis. 
  • 1.4K
  • 12 Aug 2021
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