Drosophila as a Model to Study the Mechanism of Nociception

Nociception refers to the process of encoding and processing noxious stimuli, which allow animals to detect and avoid potentially harmful stimuli. Several types of stimuli can trigger nociceptive sensory transduction, including thermal, noxious chemicals, and harsh mechanical stimulation that depend on the corresponding nociceptors. In view of the high evolutionary conservation of the mechanisms that govern nociception from Drosophila melanogaster to mammals, investigation in the fruit fly Drosophila help us understand how the sensory nervous system works and what happen in nociception. Here, we present an overview of currently identified conserved genetics of nociception, the nociceptive sensory neurons responsible for detecting noxious stimuli, and various assays for evaluating different nociception. Finally, we cover development of anti-pain drug using fly model. These comparisons illustrate the value of using Drosophila as model for uncovering nociception mechanisms, which are essential for identifying new treatment goals and developing novel analgesics that are applicable to human health

Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design

Background: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. Study design: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. Discussion: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. Trial registration: Registered on clinicaltrial.gov (NCT04561739)

Key Odorants Regulate Food Attraction in Drosophila melanogaster

In insects, the search for food is highly dependent on olfactory sensory input. Here, we investigated whether a single key odorant within an odor blend or the complexity of the odor blend influences the attraction of Drosophila melanogaster to a food source. A key odorant is defined as an odorant that elicits a difference in the behavioral response when two similar complex odor blends are offered. To validate that the observed behavioral responses were elicited by olfactory stimuli, we used olfactory co-receptor Orco mutants. We show that within a food odor blend, ethanol functions as a key odorant. In addition to ethanol other odorants might serve as key odorants at specific concentrations. However, not all odorants are key odorants. The intensity of the odor background influences the attractiveness of the key odorants. Increased complexity is only more attractive in a concentration-dependent range for single compounds in a blend. Orco is necessary to discriminate between two similarly attractive odorants when offered as single odorants and in food odor blends, supporting the importance of single odorant recognition in odor blends. These data strongly indicate that flies use more than one strategy to navigate to a food odor source, depending on the availability of key odorants in the odor blend and the alternative odor offered

The Nrf2-Keap1 pathway is activated by steroid hormone signaling to govern neuronal remodeling

10.1016/j.celrep.2021.109466Cell Reports36510946

Serotonin transporter dependent modulation of food-seeking behavior

The olfactory pathway integrates the odor information required to generate correct behavioral responses. To address how changes of serotonin signaling in two contralaterally projecting, serotonin-immunoreactive deutocerebral neurons impacts key odorant attraction in Drosophila melanogaster, we selectively alter serotonin signaling using the serotonin transporter with mutated serotonin binding sites in these neurons and analyzed the consequence on odorant-guided food seeking. The expression of the mutated serotonin transporter selectively changed the odorant attraction in an odorant-specific manner. The shift in attraction was not influenced by more up-stream serotonergic mechanisms mediating behavioral inhibition. The expression of the mutated serotonin transporter in CSD neurons did not influence other behaviors associated with food seeking such as olfactory learning and memory or food consumption. We provide evidence that the change in the attraction by serotonin transporter function might be achieved by increased serotonin signaling and by different serotonin receptors. The 5-HT1B receptor positively regulated the attraction to low and negatively regulated the attraction to high concentrations of acetic acid. In contrast, 5-HT1A and 5-HT2A receptors negatively regulated the attraction in projection neurons to high acetic acid concentrations. These results provide insights into how serotonin signaling in two serotonergic neurons selectively regulates the behavioral response to key odorants during food seeking

Nutrient removal from high ammonium swine wastewater in upflow microaerobic biofilm reactor suffered high hydraulic load

To understand the ability of an upflow microaerobic biofilm reactor (UMBR) to remove nutrient from manure-free swine wastewater rich in NH with a COD/TN ratio less than 1.00, effect of hydraulic loading rate (HLR) on the microaerobic process was evaluated with a constant reflux ratio of 25 at 25 °C. The results showed that changes in HLR had a remarkable effect on the performance of the UMBR in nutrient removal from the wastewater. With the favorable HLR 3.0 m/(m·d) (Hydraulic Retention Time (HRT) 8 h), average removal of COD, NH and TN in the microaerobic process reached 59.3%, 87.7% and 84.7%, respectively, though the COD/TN ratio was as low as 0.84. With an over HLR of 4.0 m/(m·d) (HRT decreased to 6 h), bad performance of the UMBR was observed with an average removal of COD, NH and TN as low as 45.0%, 59.0% and 57.5%, respectively. Since the HLR was decreased to 2.4 m/(m·d) (HRT 10 h), the microaerobic process regained the efficiency in nutrient removal with a removal of COD, NH and TN averaged 59.0%, 95.3% and 87.8%, respectively. The microaerobic condition allowed anammox bacteria, ammonia-oxidizing bacteria and archaea, nitrite-oxidizing bacteria and denitrifiers to all thrive in the UMBR, resulting in the efficient synchronous removal of organic carbon and nitrogen. As the dominant approach to nitrogen removal, anaerobic ammonium oxidation (anammox) pathway contributing to the TN removal in the microaerobic process exceeded 59.5% at HLR 3.0 m/(m·d). The results demonstrated that the UMBR can remove nitrogen and carbon from swine wastewater, with a suitable HLR

Cannabinoids modulate food preference and consumption in Drosophila melanogaster

10.1038/s41598-021-84180-2Scientific Reports111470

Anti-PD-1 Antibody Administration following Hip Fracture Surgery Reverses Immune Dysfunction and Decreases Susceptibility to Infection

The aim of this investigation was to assess expression of programmed death-1 (PD-1) and inflammatory status after hip fracture surgery in aged mice and to evaluate the effect of anti-PD-1 antibody intervention. Male C57BL/6 mice aged 22-28 months underwent hip fracture and femoral intramedullary pinning or a sham procedure. Expression of PD-1 was measured on CD4+ and CD8+ T cells. Additionally, the effects of anti-PD-1 antibody on lymphocyte apoptosis, cytokine production, bacterial clearance, and survival were determined. Expression of PD-1 on T cells was upregulated in mice after hip fracture and surgery compared to sham controls. Administration of anti-PD-1 antibody prevented T lymphocyte apoptosis, increased IFN-γ production in splenocytes, and decreased systemic inflammation. Antibody blockade of PD-1 significantly decreased susceptibility to bacteria and improved survival rates of aged mice after hip fracture and surgery followed by the induction of Pseudomonas aeruginosa pneumonia. This study showed that hip fracture and surgical trauma cause significant increases in PD-1 expression in aged mice. Antibody blockade of PD-1 partially reverses T cell apoptosis, decreases the systemic inflammatory response and susceptibility to bacteria, and reduces mortality