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Topic Review
Paclitaxel
Paclitaxel is an anticancer drug, extracted from the bark of the Pacific yew tree Taxus brevifolia. It was first approved in 1992 by the US Food and Drug Administration (FDA) for the treatment of advanced ovarian cancer and since then, it has been used in several cancers such as breast cancer, endometrial cancer, non-small-cell lung cancer, bladder cancer, cervical carcinoma, and AIDS-related Kaposi sarcoma.
  • 981
  • 28 Feb 2022
Topic Review
Proteopathy
In medicine, proteopathy (/proʊtiːˈɒpəθiː/; from proteo- [pref. protein]; -pathy [suff. disease]; proteopathies pl.; proteopathic adj) refers to a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function) or they can lose their normal function. The proteopathies (also known as proteinopathies, protein conformational disorders, or protein misfolding diseases) include such diseases as Creutzfeldt–Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term proteopathy was first proposed in 2000 by Lary Walker and Harry LeVine. The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose. In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross-polarized light after staining with the dye Congo red, as well as a fibrillar ultrastructure when viewed with an electron microscope. However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign.
  • 981
  • 24 Nov 2022
Topic Review
Acute Kidney Injury (AKI)
Acute kidney injury (AKI) is characterized by an acute loss of renal function. In clinical practice, AKI is defined by an elevation of creatinine plasma concentration above ≥0.3 mg/dL in the first 48 h, an urine volume below 0.5 mL/kg/h for 6 h, or an 1.5 fold increase in serum creatinine as compared with the baseline values.
  • 980
  • 01 Feb 2021
Topic Review
Microbiota-Mitochondria Inter-Talk
The rising prevalence of obesity and type 2 diabetes (T2D) is a growing concern worldwide. New discoveries in the field of metagenomics and clinical research have revealed that the gut microbiota plays a key role in these metabolic disorders. The mechanisms regulating microbiota composition are multifactorial and include resistance to stress, presence of pathogens, diet, cultural habits and general health conditions. Recent evidence has shed light on the influence of microbiota quality and diversity on mitochondrial functions. Of note, the gut microbiota has been shown to regulate crucial transcription factors, coactivators, as well as enzymes implicated in mitochondrial biogenesis and metabolism. Moreover, microbiota metabolites seem to interfere with mitochondrial oxidative/nitrosative stress and autophagosome formation, thus regulating the activation of the inflammasome and the production of inflammatory cytokines, key players in chronic metabolic disorders. This review focuses on the association between intestinal microbiota and mitochondrial function and examines the mechanisms that may be the key to their use as potential therapeutic strategies in obesity and T2D management.
  • 979
  • 21 Oct 2020
Topic Review
Obesity and Mood Disorders
Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this study, we focused on the potential roles of DNA methylation on mood disorders and obesity development.
  • 978
  • 05 Jan 2021
Topic Review
Diabetes Mellitus and COVID-19
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a global pandemic. The hyperglycemia in patients with diabetes mellitus (DM) substantially compromises their innate immune system. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) receptors to enter the affected cell. Uncontrolled hyperglycemia-induced glycosylation of ACE2 and the S protein of SARS-CoV-2 could facilitate the binding of S protein to ACE2, enabling viral entry. Downregulation of ACE2 activity secondary to SARS-CoV-2 infection, with consequent accumulation of angiotensin II and metabolites, eventually leads to poor outcomes. The altered binding of ACE2 with SARS-CoV-2 and the compromised innate immunity of patients with DM increase their susceptibility to COVID-19; COVID-19 induces pancreatic β-cell injury and poor glycemic control, which further compromises the immune response and aggravates hyperglycemia and COVID-19 progression, forming a vicious cycle. Sequential cleavage of viral S protein by furin and transmembrane serine protease 2 (TMPRSS2) triggers viral entry to release the viral genome into the target cell. Hence, TMPRSS2 and furin are possible drug targets. As type 1 DM exhibits a Th1-driven autoimmune process, the relatively lower mortality of COVID-19 in type 1 DM compared to type 2 DM might be attributed to an imbalance between Th1 and Th2 immunity. The anti-inflammatory effects of dipeptidyl peptidase-4 inhibitor may benefit patients with DM and COVID-19. The potential protective effects of sodium–glucose cotransporter-2 inhibitor (SGLT2i), including reduction in lactate level, prevention of lowering of cytosolic pH and reduction in pro-inflammatory cytokine levels may justify the provision of SGLT2i to patients with DM and mild or asymptomatic COVID-19. For patients with DM and COVID-19 who require hospitalization, insulin-based treatment is recommended with cessation of metformin and SGLT2i. Further evidence from randomized or case–control clinical trials is necessary to elucidate the effectiveness and pitfalls of different types of medication for DM.
  • 975
  • 22 Dec 2020
Topic Review
Thoracic Aortic Aneurysms
Thoracic aortic aneurysms (TAA) are permanent and localized dilations of the aorta that predispose patients to a life-threatening risk of aortic dissection or rupture. The identification of pathogenic variants that cause hereditary forms of TAA has delineated fundamental molecular processes required to maintain aortic homeostasis. Vascular smooth muscle cells (VSMCs) elaborate and remodel the extracellular matrix (ECM) in response to mechanical and biochemical cues from their environment. Causal variants for hereditary forms of aneurysm compromise the function of gene products involved in the transmission or interpretation of these signals, initiating processes that eventually lead to degeneration and mechanical failure of the vessel. These include mutations that interfere with transduction of stimuli from the matrix to the actin–myosin cytoskeleton through integrins, and those that impair signaling pathways activated by transforming growth factor-β (TGF-β).
  • 975
  • 16 Feb 2021
Topic Review
Melanoma Single-Cell Biology
Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8+ T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.
  • 971
  • 25 Feb 2021
Topic Review
GABAB Receptor
The γ-aminobutyric acid (GABA) type B receptor (GABAB-R) belongs to class C of the G-protein coupled receptors (GPCRs). Together with the GABAA receptor, the receptor mediates the neurotransmission of GABA, the main inhibitory neurotransmitter in the central nervous system (CNS).
  • 971
  • 01 Dec 2021
Topic Review
Enteric Fever Progression
In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This entry attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species.
  • 971
  • 23 Feb 2021
Topic Review
Mucoadhesive Chitosan Nanoparticles
Chitosan is a polysaccharide polymer produced by alkaline deacetylation of chitin. It has a positive charge that may interact with negatively charged mucosal surfaces.
  • 968
  • 18 Mar 2021
Topic Review
Serology in SARS-CoV-2 Infection
SARS-CoV-2/Coronavirus 2019 (COVID-19) is responsible for the pandemic, which started in December 2019. In addition to the typical respiratory symptoms, this virus also causes other severe complications, including neurological ones. In diagnostics, serological and polymerase chain reaction tests are useful not only in detecting past infections but can also predict the response to vaccination. It is now believed that an immune mechanism rather than direct viral neuroinvasion is responsible for neurological symptoms. For this reason, it is important to assess the presence of antibodies not only in the serum but also in the cerebrospinal fluid (CSF), especially in the case of neuro-COVID. A particular group of patients are people with multiple sclerosis (MS) whose disease-modifying drugs weaken the immune system and lead to an unpredictable serological response to SARS-CoV-2 infection. Based on available data, the article summarizes the current serological information concerning COVID-19 in CSF in patients with severe neurological complications and in those with MS. 
  • 968
  • 06 Feb 2022
Topic Review
Zebrafish Models for Skeletal Muscle Senescence
Aging and sarcopenic changes in skeletal muscles not only reduce locomotor activities in elderly people but also increase the chance of trauma, such as bone fractures, and the incidence of other diseases, such as metabolic syndrome, due to reduced physical activity.
  • 968
  • 22 Dec 2022
Topic Review
Mind-Body Interventions for Psoriasis
Psoriasis is a chronic inflammatory disorder involving but not limited to the skin, with decisive immunological and genetic elements, upon which environmental factors may act. Conventional therapies include topical, systemic, and biologic agents. However, some of these therapies may trigger adverse effects of varying severity, at times may not be effective, or simply involve too high costs. For this reason, many patients resort to complementary and alternative medicine (CAM) to treat this pathology, with acupuncture, cupping, psychotherapy, and climatotherapy to name the most common procedures. In the following paragraphs, the CAM methods used for psoriasis are evaluated with respect to their efficacy, as shown in the English literature.
  • 963
  • 07 May 2021
Topic Review
ACL Repair
The anterior cruciate ligament ( ACL) is able to heal and subsequently restabilize the knee. 
  • 961
  • 14 Apr 2021
Topic Review
Probiotics and Vacccines
It has been recognized that microbiota plays a key role in shaping immune system maturation and activity. Since probiotic administration influences the microbiota composition and acts as a biological response modifier, the efficacy of an adjuvant for boosting vaccine-specific immunity is investigated.
  • 961
  • 10 Aug 2021
Topic Review
Acute Biphenotypic Leukaemia
Acute biphenotypic leukaemia is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage". The direct reasons leading to BAL are still not clear. BAL can be de novo or secondary to previous cytotoxic therapy. Many factors, such viruses, hereditary factors, and radiation, might have a relationship with BAL. BAL is hard to treat. Usually the chemotherapy is chosen according to the morphology of the blast (ALL or AML). A blood-forming stem-cell transplantation is highly recommended. About 5% of acute leukaemia cases are BAL. BAL can occur in all ages of people but occurs more in adults than in children.
  • 961
  • 11 Nov 2022
Topic Review
Long-term Complications of Standing
The long-term complications of standing are the conditions that may arise after prolonged time in a standing or upright position including standing, walking or running. Many of the complications come from prolonged standing (more the 60% of a work day) that is repeated several times a week. There are many different jobs that require prolonged standing. These included: "retail staff, Baristas, bartenders, assembly line workers, security staff, engineers, catering staff, library assistants, hair stylists and laboratory technicians." Cornell university has calculated that "Standing requires ~20% more energy than sitting".
  • 960
  • 14 Oct 2022
Topic Review
Universal Influenza Vaccine Human Trials
On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look forward, there are currently three vaccines in phase III clinical trials which could provide significant improvement over seasonal influenza vaccines. This systematic review of universal influenza vaccine clinical trials during the 2010–2019 decade provides an update on the progress towards an improved influenza vaccine.
  • 958
  • 12 May 2021
Topic Review
Vaccine Court
The Office of Special Masters of the U.S. Court of Federal Claims, popularly known as "vaccine court", administers a no-fault system for litigating vaccine injury claims. These claims against vaccine manufacturers cannot normally be filed in state or federal civil courts, but instead must be heard in the U.S. Court of Federal Claims, sitting without a jury. The National Vaccine Injury Compensation Program (VICP or NVICP) was established by the 1986 National Childhood Vaccine Injury Act (NCVIA), passed by the United States Congress in response to a threat to the vaccine supply due to a 1980s scare over the DPT vaccine. Despite the belief of most public health officials that claims of side effects were unfounded, large jury awards had been given to some plaintiffs, most DPT vaccine makers had ceased production, and officials feared the loss of herd immunity. No evidence has been found to support a link between autism spectrum disorders and vaccines, and the scientific consensus is that routine childhood vaccines have no link to the development of autism. Despite this, some parents of children with autism spectrum disorders have attributed the disorders' onset to vaccines, and more than 5,300 parents have filed petitions at the vaccine court. The vaccine court dismissed the suits and ruled that the MMR vaccine does not cause autism.
  • 958
  • 30 Nov 2022
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