Antimicrobial peptide1

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

We identified low-molecular weight compounds derived from the antimicrobial peptide human neutrophil peptide-1 that bind to Lipid II, an essential precursor of bacterial cell wall biosynthesis. These compounds act as antibacterials on multiple biosynthesis pathways with specificity against gram-positive organisms. Here, we have tested a small subset of our most promising leads against the bacterium Clostridium perfringens and sporozoites of Eimeria tenella, an intracellular protozoan parasite that causes intestinal disease in poultry. We found one compound, 1611-0203 (2-{2,3,5,6-tetrafluoro-4-[2,3,5,6-tetrafluoro-4-(2-hydroxyphenoxy)phenyl]phenoxy}phenol), specifically to inhibit growth of both agents out of all compounds tested. Additionally, compound 1611-0203 inhibits Staphylococcus aureus and Enterococcus spp. Mechanism-of-action studies further reveal that 1611-0203 affects cell wall biosynthesis and inhibits additional biosynthetic pathways. Combined, our results indicate that compounds such as 1611-0203 have therapeutic potential to act as anti-infectives against various organisms simultaneously.

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate's role in host physiology, metabolic, and cardiovascular health.