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Topic Review
Ibrexafungerp (formerly SCY-078 or MK-3118)
Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug-drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.
  • 1.5K
  • 19 Mar 2021
Topic Review
Oral Health and Gastro-intestinal Diseases
Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. The salivary microbiota can affect the development of the intestinal microbiota, as saliva flows through the gastrointestinal tract, allowing the bacteria present in it to easily reach the intestine. The DNA of bacteria belonging to the salivary microbiota is detectable in the gut even in low concentrations.
  • 1.5K
  • 01 Jun 2021
Topic Review
Epicardial Thoracoscopic Ablation
In this study we evaluated atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. This was a prospective, multicenter, observational study to recruit patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation. About 27 patients, responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to non responders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037-1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126-2.738), p < 0.05), BNP (HR 1.945 (1.895-1.999), p < 0.05), and SERCA (HR 1.763 (1.167-2.663), p < 0.05) were predictive of AF recurrence. Therefore, our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Thus, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.
  • 1.5K
  • 28 Oct 2020
Topic Review
Babesia spp. Identification
Babesiosis is considered one of the main vector-borne diseases caused by intraerythrocytic parasites, just behind malaria disease whose etiological agent is transmitted by mosquitoes.
  • 1.5K
  • 24 Feb 2021
Topic Review
Invasion of Embryo’s Nutritional
Historically, invasion of placental trophoblasts was thought to be extremely specific, only invading into the connective tissues of the maternal uterus finally reaching and transforming the uterine spiral arteries. Only recently, identification of new routes of trophoblast invasion into different structures of the maternal uterus has been achieved. Thorough morphological analysis has resulted in the identification of trophoblasts invading into glands, veins and lymph vessels of the uterine wall. These new routes pave the way for a re-evaluation of trophoblast invasion during normal placental development. Of course, such new routes of trophoblast invasion may well be altered, especially in pregnancy pathologies such as intra-uterine growth restriction, preeclampsia, early and recurrent pregnancy loss, stillbirth and spontaneous abortion. Maybe one or more of these pregnancy pathologies show alterations in different pathways of trophoblast invasion and thus, etiologies may need to be redefined and new therapies may be developed.
  • 1.5K
  • 30 Oct 2020
Topic Review
Interferon Lambda
Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. Type III IFN elicit fewer inflammatory responses than the Type I IFN and are gaining interest as antiviral treatments.
  • 1.5K
  • 08 Feb 2021
Topic Review
Mitochondrial DNA and COVID-19
The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. It should be noted the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. 
  • 1.5K
  • 18 Sep 2021
Topic Review
Protofibrils in Alzheimer’s Disease
Worldwide, Alzheimer's disease (AD) is the most common age-related neurodegenerative disease and is characterized by unique pathological hallmarks in the brain, including plaques composed of amyloid β-protein (Aβ) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that Aβ is responsible for the pathogenesis of AD (i.e., the amyloid hypothesis). Indeed, Aβ molecules tend to aggregate, forming oligomers, protofibrils, and mature fibrils. However, while these Aβ species form amyloid plaques of the type implicated in AD neurodegeneration, recent clinical trials designed to reduce the production of Aβ and/or the plaque burden have not demonstrated clinical efficacy. In addition, recent studies using synthetic Aβ peptides, cell culture models, Arctic transgenic mice, and human samples of AD brain tissues have suggested that the pre-fibrillar forms of Aβ, particularly Aβ protofibrils, may be the most critical species, compared with extracellular fibrillar forms. We recently reported that protofibrils of Aβ1-42 disturbed membrane integrity by inducing reactive oxygen species generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and synaptic toxicity. Therefore, the therapeutic reduction of protofibrils may prevent the progression of AD by ameliorating neuronal damage and cognitive dysfunction through multiple mechanisms.
  • 1.5K
  • 21 Apr 2021
Topic Review
Age-Related Hearing Loss
Age-related hearing impairment, also referred to as presbycusis, is the most common sensory impairment seen in the elderly. As our cochlea, the peripheral organ of hearing, ages, we tend to experience a decline in hearing and are at greater risk of cochlear sensory-neural cell degeneration and exacerbated age-related hearing impairments (e.g., gradual hearing loss, deterioration in speech comprehension, difficulty in the localization sound sources, and ringing sensations in the ears). Here, we outline recent research into major causal factors of age-related hearing loss including both extrinsic (e.g. noise and ototoxic medication), and intrinsic factors (e.g. genetic predisposition, epigenetic factors and aging).
  • 1.5K
  • 23 Oct 2020
Topic Review
Chronic Arthritis
Chronic arthritis is not a singular disorder; it is stands for multifaceted autoimmune and inflammatory disabling conditions causing joint pain or joint deformity. Chronic arthritis in children is diagnosed when all three of the following criteria are met. First, the age of onset is younger than 16 years. Second, arthritis includes swelling or effusion, or presence of two or more of the following: a) limitation of range of motion; b) tenderness or pain on motion; c) increased heat in one or more joints; and third, the duration of disease is 6 weeks or longer. Juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) are two major groups with chronic joint pain and inflammation, extra-articular manifestations, and high risk of comorbidities, which can cause physical and ocular disability, as well as create great socio-economic pressure worldwide. The pathogenesis of arthritis manifested in childhood and adulthood is multifactorial, unclear, and overly complex, in which immunity plays an important role. Although there are more and more biological agents with different mechanisms of action for the treatment of arthritis, the results are not as expected, because there are partial responses or non-responsive patients to these compounds, high therapeutic costs, side effects, and so on; therefore, we must turn our attention to other therapeutic modalities. Updating knowledge on molecular and cellular mechanisms in the comparative pathogenesis of chronic arthritis in both children and adults is necessary in the early and correct approach to treatment. Photobiomodulation (PBM) represents a good option, offering cost-effective advantages over drug therapy, with a quicker, more positive response to treatment and no side effects. The successful management of PBM in arthritis is based on the clinician’s ability to evaluate correctly the inflammatory status of the patient, to seek the optimal solution, to choose the best technology with the best physical parameters, and to select the mode of action to target very precisely the immune system and the signaling pathways at the molecular level with the exact amount of quantum light energy in order to obtain the desired immune modulation and the remission of the disease. Light is a very powerful tool in medicine because it can simultaneously target many cascades of immune system activation in comparison with drugs, so PBM can perform very delicate tasks inside our cells to modulate cellular dysfunctions, helping to initiate self-organization phenomena and finally, healing the disease.
  • 1.5K
  • 21 Sep 2020
Topic Review
Parkinson’s Disease Chronic Pain Treatment
Neurological disorders, including Parkinson’s disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson’s patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients.
  • 1.5K
  • 07 Dec 2020
Topic Review
Mitochondrial Permeability Transition Pores
Substantial evidence has revealed that mitochondrial permeability transition pores (mPTPs) are associated with signaling pathway of cardioprotective models and seem to be an end-effector of cardioprotection. Experimental streptozotocin-induced diabetes mellitus (D) was shown to provide sufficient protection to the myocardium via compensatory mechanisms enabling mitochondria to produce energy under pathological conditions during the acute phase. The hypothesized involvement of mPTPs in these processes prompted us to use liquid chromatography and mass spectrometry-based proteomic analysis to investigate the effects of the acute-phase D condition on the structural and regulatory components of this multienzyme complex and the changes caused by compensation events. We detected ADT1, ATP5H, ATPA, and ATPB as the most abundant mPTP proteins. The between-group differences in protein abundance of the mPTP complex as a whole were significantly upregulated in the D group when compared with the control (C) group (p = 0.0106), but fold changes in individual protein expression levels were not significantly altered except for ATP5H, ATP5J, and KCRS. However, none of them passed the criterion of a 1.5-fold change in differential expression for biologically meaningful change. Visualization of the (dis-)similarity between the C and D groups and pairwise correlations revealed different patterns of protein interactions under the C and D conditions which may be linked to endogenous protective processes, of which beneficial effects on myocardial function were previously confirmed. Our results point to the involvement of mPTP proteins in the endogenous protective processes leading to the preservation of myocardial function under pathological conditions. Proteomic studies with respect to the correlation of mPTP proteins were shown to be one of the most promising options for the advancement of mPTP regulation mechanisms. Subtle changes in mPTP protein expressions, as well as mutual relationships between proteins, may be sufficient to contribute to preserving mitochondrial energy metabolism under the increased energy load represented by experimental D.
  • 1.4K
  • 29 Oct 2020
Topic Review
Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from SMN1 gene mutations or deletions. However, patients always harbor various copies of SMN2, an almost identical but functionally deficient copy of the gene. A genotype–phenotype correlation suggests that SMN2 is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of SMN1 and SMN2 genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing.
  • 1.4K
  • 30 Oct 2020
Topic Review
Flaviviruses
Flaviviruses are arthropod-borne RNA viruses that have been used extensively to study host antiviral responses. Often selected just to represent standard single-stranded positive-sense RNA viruses in early studies, the Flavivirus genus over time has taught us how truly unique it is in its remarkable ability to target not just the RNA sensory pathways but also the cytosolic DNA sensing system for its successful replication inside the host cell. This review summarizes the main developments on the unexpected antagonistic strategies utilized by different flaviviruses, with RNA genomes, against the host cyclic GAMP synthase (cGAS)/stimulator of interferon genes (STING) cytosolic DNA sensing pathway in mammalian systems. On the basis of the recent advancements on this topic, we hypothesize that the mechanisms of viral sensing and innate immunity are much more fluid than what we had anticipated, and both viral and host factors will continue to be found as important factors contributing to the host innate immune system in the future.
  • 1.4K
  • 03 Dec 2020
Topic Review
Parkinson’s Disease
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of the population over 60 years of age. Clinically, PD is characterized mainly by the presence of motor symptoms, but a wide range of non-motor symptoms not only accompany the disease, but many of them even prevent the occurrence of motor symptoms. Despite many efforts, current medicine fails, not only in the treatment of PD, but in the early diagnosis of the disease. Current treatment is mainly based on symptomatic treatment or treatment with levodopa (L-DOPA) but does not focus on the pathogenesis of the disease itself. The presence of non-motor symptoms such as gastrointestinal dysfunction, which occurs up to 20 years before the onset of motor symptoms themselves, provides a sufficiently wide window of early diagnosis and thus potential early therapy for these patients. α-synuclein (α-Syn) is one of the candidates for a biomarker of PD. Mutations in its gene are associated with the familial form of PD as well as conformational changes in the protein and with its ability to oligomerize and fibrillate and form Lewy bodies (LB) and Lewy neurites (LN). It is LB and LN that are considered to be one of the most important pathological features of the disease, where α-Syn is the major component of these pathological structures. Its direct association with the pathogenesis of the disease together with the fact that in addition to brain structures, α-Syn is present in body fluids as well as in peripheral tissues such as gastrointestinal (GIT) tissues even enhances its potential use in early diagnosis of the disease. The diagnosis of the disease is also complicated by the similarity of clinical, cognitive, and neuropathological features of PD with other neurodegenerative diseases. In this context, various α-Syn strains have been identified based on the ability of α-Syn to form several types of fibrillar structures (strains) with different conformational, biological, and biochemical properties. And it is these differences that may be key to the correct early diagnosis of PD.
  • 1.4K
  • 16 Sep 2023
Topic Review
IPF
In idiopathic pulmonary fibrosis (IPF), several factors may have a negative impact on the nutritional status, including an increased respiratory muscles load, release of inflammation mediators, the coexistence of hypoxemia, and physical inactivity. Nutritional abnormalities also have an impact on IPF clinical outcomes. Given the relevance of nutritional status in IPF patients, we sought to focus on some critical issues, highlighting what is known and what should be further learned about these issues. We revised scientific literature published between 1995 and August 2019 by searching on Medline/PubMed and EMBASE databases including observational and interventional studies. We conducted a narrative review on nutritional assessment in IPF, underlining the importance of nutritional evaluation not only in the diagnostic process, but also during follow-up. We also highlighted the need to keep a high level of attention on cardiovascular comorbidities. We also focused on current clinical treatment in IPF with Nintedanib and Pirfenidone and management of gastrointestinal adverse events, such as diarrhea, induced by these antifibrotic drugs. Finally, we concentrated on the importance of pulmonary rehabilitation program, including nutritional assessment, education and behavioral change, and psychological support among its essential components. More attention should be devoted to the assessment of the undernutrition and overnutrition, as well as of muscle strength and physical performance in IPF patients, taking also into account that an adequate clinical management of gastrointestinal complications makes IPF drug treatments more feasible. 
  • 1.4K
  • 30 Oct 2020
Topic Review
Colorectal Cancer
Colorectal cancer (CRC) is the third leading cause of cancer death in the world. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.
  • 1.4K
  • 09 Apr 2021
Topic Review
Cripto-1 in Tumor Progression
Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients. 
  • 1.4K
  • 06 Sep 2021
Topic Review
Hypereosinophilia and Hypereosinophilic Syndromes
Hypereosinophilia (HE) is a heterogeneous condition with a persistent elevated eosinophil count of >350/mm3, which is reported in various (inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. HE may be associated with tissue or organ damage and, in this case, the disorder is classified as hypereosinophilic syndrome (HES).
  • 1.4K
  • 15 Jun 2021
Topic Review
Photobiomodulation in Dermatology
Photobiomodulation (PBM), formerly known as low-level laser light therapy (LLLT), is a safe phototherapy technique that uses wavelengths of the visible light spectrum which includes red light (RL, 620–700 nm) and near-infrared (NIR, 700–1440 nm). This treatment modality has been used in dermatology, both in clinical settings and at home. PBM involves the use of various light sources, including low-level lasers (LLL) and light-emitting diodes (LED), to deliver therapeutic light. Reviews on the matter have already been conducted.
  • 1.4K
  • 06 Nov 2024
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