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Topic Review
Targeting Gut in Obesity: Signals from Inner Surface
Obesity is caused by prolonged energy surplus. Current anti-obesity medications are mostly centralized around the energy input part of the energy balance equation by increasing satiety and reducing appetite. Our gastrointestinal tract is a key organ for regulation of food intake and supplies a tremendous number of circulating signals that modulate the activity of appetite-regulating areas of the brain by either direct interaction or through the vagus nerve. Intestinally derived messengers are manifold and include absorbed nutrients, microbial metabolites, gut hormones and other enterokines, collectively comprising a fine-tuned signalling system to the brain. After a meal, nutrients directly interact with appetite-inhibiting areas of the brain and induce satiety. However, overall feeding behaviour also depends on secretion of gut hormones produced by highly specialized and sensitive enteroendocrine cells. Moreover, circulating microbial metabolites and their interactions with enteroendocrine cells further contribute to the regulation of feeding patterns. Current therapies exploiting the appetite-regulating properties of the gut are based on chemically modified versions of the gut hormone, glucagon-like peptide-1 (GLP-1) or on inhibitors of the primary GLP-1 inactivating enzyme, dipeptidyl peptidase-4 (DPP-4). The effectiveness of these approaches shows that that the gut is a promising target for therapeutic interventions to achieve significant weigh loss. 
  • 549
  • 24 Jan 2022
Topic Review
The Medicinal Properties for FDA-Approved Oximes
Organophosphate (OP) poisoning continues to be a major threat to humans. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are β-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens.
  • 1.0K
  • 21 Jan 2022
Topic Review
PTP1B Inhibitors
Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in type 2 diabetes mellitus (T2DM), as its overexpression may induce insulin resistance.
  • 432
  • 21 Jan 2022
Topic Review
Tumor Necrosis Factor and Lymphotoxin
The tumor necrosis factor (TNF) ligand family includes 19 ligands, which each contain a C-terminal TNF homology domain (THD). Each ligand binds to one or multiple TNF receptors (TNFR), containing extracellular cysteine-rich domains (CRD) for ligand binding. Tumor necrosis factor (TNF or TNF-α) and lymphotoxin (LT) are the first two cytokines that have been characterized as TNF superfamily members. They have a homologous amino acid sequence and were both discovered based on their anti-tumor effects. Moreover, both ligands bind to TNF receptor type 1 and type 2 (TNFR1 and TNFR2) and mediate similar cell signaling transduction.
  • 642
  • 19 Jan 2022
Topic Review
Microbiota
The human gut microflora comprises over 1000 species and more than 7000 strains, representing 1013–1014 bacterial cells, which is ten times more numerous than other cells. Healthy gut microbiota is mainly composed of the phyla Firmicutes and Bacteroidetes, representing around 90% of the human gut flora, followed by Actinobacteria, Verrucomicrobia, and Proteobacteria.
  • 985
  • 18 Jan 2022
Topic Review
Plectranthus neochilus Schltr
Plectranthus neochilus Schltr. (Lamiaceae) is a plant recently introduced in Cuba. Worldwide, it is an ethnomedicinal alternative for its use against microbial infections, but the Cuban population use the extracts to treat sleep disorders. To address this apparent incongruity, four collections (from different seasonal conditions in the year) of Cuban P. neochilus cultivars were analyzed in terms of their pharmacognostic characteristics. 
  • 1.2K
  • 18 Jan 2022
Topic Review
FAAH, MAGL, and DAGL in Obesity Treatment
The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis and may affect hunger, caloric intake, and nutrient absorption. Obesity has been associated with higher levels of the endogenous cannabinoid transmitters (endocannabinoids). Therefore, the ECS is an important target in obesity treatment. Modulating the enzymes that synthesize and degrade endocannabinoids, namely fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and diacylglycerol lipase (DAGL), may be a promising strategy to treat obesity.
  • 424
  • 18 Jan 2022
Topic Review
Metabolic Disorders
Metabolic syndrome (MS) is a cluster of different metabolic disorders, obesity, hypertriglyceridemia, dyslipidemia, hyperglycemia, insulin resistance, and hypertension, that lead to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases (CVDs) [1]. In Western countries, the increased prevalence of CVDs and atherosclerosis, which actually accounted for approximately 50% of all CVD-related deaths, is further sustained by a sedentary lifestyle and high-calorie food intake [3]. It has been estimated that, in 2016, more than 1.9 billion adults (>18 of age) were overweight and 650 million were obese. A diet rich in fat and sugar and a lack of exercise leads to the accumulation of visceral fat, the development of liver steatosis, and the onset of MS risk factors. Since the prevalence of all these metabolic dysfunctions increased worldwide in the last years, it is essential to find new strategies for preventing or treating obesity, dyslipidemia, and insulin resistance [3], e.g. nutritional intervention and functional foods.
  • 945
  • 16 Jan 2022
Topic Review
Clotting Dysfunction in Sepsis
Sepsis is regarded as one of the main causes of death among the critically ill. Pathogen infection results in a host-mediated pro-inflammatory response to fight infection; as part of this response, significant endogenous reactive oxygen (ROS) and nitrogen species (RNS) production occurs, instigated by a variety of sources, including activated inflammatory cells, such as neutrophils, platelets, and cells from the vascular endothelium. Inflammation can become an inappropriate self-sustaining and expansive process, resulting in sepsis. Patients with sepsis often exhibit loss of aspects for normal vascular homeostatic control, resulting in abnormal coagulation events and development of disseminated intravascular coagulation. Diagnosis and treatment of sepsis remains a significant challenge for health care providers globally. Targeting the drivers of excessive oxidative/nitrosative stress using antioxidant treatments might be a therapeutic option.
  • 324
  • 14 Jan 2022
Topic Review
Interactions of Analgesics with Cisplatin
Cisplatin (CDDP), one of the most eminent cancer chemotherapeutic agents, has been successfully used to treat more than half of all known cancers worldwide. Despite its effectiveness, CDDP might cause severe toxic adverse effects on multiple body organs during cancer chemotherapy, including the kidneys, heart, liver, gastrointestinal tract, and auditory system, as well as peripheral nerves causing severely painful neuropathy. The latter, among other pains patients feel during chemotherapy, is an indication for the use of analgesics during treatment with CDDP. Different types of analgesics, such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS), and narcotic analgesics, could be used according to the severity of pain. Administered analgesics might modulate CDDP’s efficacy as an anticancer drug. NSAIDS, on one hand, might have cytotoxic effects on their own and few of them can potentiate CDDP’s anticancer effects via inhibiting the CDDP-induced cyclooxygenase (COX) enzyme, or through COX-independent mechanisms. On the other hand, some narcotic analgesics might ameliorate CDDP’s anti-neoplastic effects, causing chemotherapy to fail. Concerning safety, some analgesics share the same adverse effects on normal tissues as CDDP, augmenting its potentially hazardous effects on organ impairment.
  • 278
  • 14 Jan 2022
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