•Omega-3 eCBs are endogenously synthesized from omega-3 fatty acids in the body.•Omega-3 eCBs and their derivatives play a role in different disease states such as pain, inflammation and ...cancer.•Omega-3 eCBs are oxidatively metabolized by eicosanoid synthesizing enzymes - lipoxygenase and cytochrome P450 epoxygenase.•Omega-3 eCBs and their derivatives demonstrate diverse functions and receptor interactions.
Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa, as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). The consumption of omega-3 fatty acids shifts the balance towards a higher proportion of omega-3 eCBs, whose physiological functions warrants further investigation. Herein, we review the discovery of omega-3 fatty acid derived eCBs that are generated from long chain omega-3 PUFAs - docosahexaenoyl ethanolamide (DHA-EA or synaptamide), docosahexanoyl-glycerol (DHG), eicosapentaenoyl ethanolamide (EPA-EA) and eicosapentanoylglycerol (EPG). Furthermore, we outline the lesser known omega-3 eCB-like molecules that arise from the conjugation of omega-3 fatty acids with neurotransmitters serotonin and dopamine - DHA-serotonin (DHA-5HT), DHA-dopamine (DHA-DA), EPA-serotonin (EPA-5HT) and EPA-dopamine (EPA-DA). Additionally, we describe the role of omega-3 eCBs and their derivatives in different disease states, such as pain, inflammation and cancer. Moreover, we detail the formation and potential physiological roles of the oxidative metabolites that arise from the metabolism of omega-3 eCBs by eicosanoid synthesizing enzymes - cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450). In summary, we outline the novel findings regarding a growing class of signaling molecules that can control the physiological and pathophysiological processes in the body.
COVID-19 pandemic has significantly impacted on every aspect of mankind. Education sector is not left behind. Many education organizations around the world are closed now. The whole education system ...specially teaching-learning, knowledge sharing, evaluation methods etc. have been shifted from offline to online platform. Teachers are forced to work from home and they persistently trying to adopt new modes of virtual teaching. The new normal working process is challenging for them in keeping their motivation to work. Lack of physical face to face communication with students, colleagues, the Principals is affecting in teachers' motivation to work. This research study is an explorative case study and the sample was selected by using purposive sampling technique. For this study 9 female teachers of a Kolkata based college, West Bengal were chosen. They were interviewed on telephone to collect data. In-depth interview derived findings are divided into themes and discussed. This study will be beneficial for the higher education authority to concentrate on the role of virtual interpersonal communication in respect of teachers' motivation.
Chlorophyll degradation is the most obvious hallmark of leaf senescence. Phyllobilins, linear tetrapyrroles that are derived from opening of the chlorin macrocycle by the Rieske-type oxygenase ...PHEOPHORBIDE a OXYGENASE (PAO), are the end products of chlorophyll degradation. Phyllobilins carry defined modifications at several peripheral positions within the tetrapyrrole backbone. While most of these modifications are species-specific, hydroxylation at the C32 position is commonly found in all species analyzed to date. We demonstrate that this hydroxylation occurs in senescent chloroplasts of Arabidopsis thaliana. Using bell pepper (Capsicum annuum) chromoplasts, we establish that phyllobilin hydroxylation is catalyzed by a membrane-bound, molecular oxygen-dependent, and ferredoxin-dependent activity. As these features resemble the requirements of PAO, we considered membrane-bound Rieske-type oxygenases as potential candidates. Analysis of mutants of the two Arabidopsis Rieske-type oxygenases (besides PAO) uncovered that phyllobilin hydroxylation depends on TRANSLOCON AT THE INNER CHLOROPLAST ENVELOPE55 (TIC55). Our work demonstrates a catalytic activity for TIC55, which in the past has been considered as a redox sensor of protein import into plastids. Given the wide evolutionary distribution of both PAO and TIC55, we consider that chlorophyll degradation likely coevolved with land plants.
Cytochrome P450 reductase, which delivers electrons from NADPH to microsomal P450s, consists of a single polypeptide that contains both FAD and FMN. The bacterial P450cin utilizes a similar electron ...transport system except the FAD/FMN reductase consists of two separate polypeptides where the FMN protein, cindoxin, shuttles electrons between the FAD-containing cindoxin reductase and P450cin. Here we characterize the kinetics and specificity of electron transfer between cindoxin and P450cin as well as discuss the influence of possible binding surface interactions using homology models.
Lipid composition and macromolecular crowding are key external effectors of protein activity and stability whose role varies between different proteins. Therefore, it is imperative to study their ...effects on individual protein function. CYP2J2 is a membrane‐bound cytochrome P450 in the heart involved in the metabolism of fatty acids and xenobiotics. In order to facilitate this metabolism, cytochrome P450 reductase (CPR), transfers electrons to CYP2J2 from NADPH. Herein, we use nanodiscs to show that lipid composition of the membrane bilayer affects substrate metabolism of the CYP2J2‐CPR nanodisc (ND) system. Differential effects on both NADPH oxidation and substrate metabolism by CYP2J2‐CPR are dependent on the lipid composition. For instance, sphingomyelin containing nanodiscs produced more secondary substrate metabolites than discs of other lipid compositions, implying a possible conformational change leading to processive metabolism. Furthermore, we demonstrate that macromolecular crowding plays a role in the lipid‐solubilized CYP2J2‐CPR system by increasing the Km and decreasing the Vmax, and effect that is size‐dependent. Crowding also affects the CYP2J2‐CPR‐ND system by decreasing both the Km and Vmax for Dextran‐based macromolecular crowding agents, implying an increase in substrate affinity but a lack of metabolism. Finally, protein denaturation studies show that crowding agents destabilize CYP2J2, while the multidomain protein CPR is stabilized. Overall, these studies are the first report on the role of the surrounding lipid environment and macromolecular crowding in modulating enzymatic function of CYP2J2‐CPR membrane protein system.
Postoperative residual curarization (PORC) and the impact of the coadministration of intravenous calcium along with an acetylcholinesterase inhibitor on it are not well addressed. Extensive ...electronic database screening was done until October 7, 2022 after enlisting the protocol of this systematic review in PROSPERO (CRD42021274879). Randomized controlled trials (RCTs) evaluating the impact of intravenous calcium and neostigmine coadministration on neuromuscular recovery were included in this meta-analysis. Our search retrieved four RCTs with a total of 266 patients. The application of calcium shortened the neuromuscular recovery time (SMD = -2.13, 95% confidence interval CI: -2.66 to -1.59,
= 66%) and reduced the risk of PORC at 5 min (odds ratio OR = 0.21, 95% CI: 0.10-0.46,
= 0%), with an improved train-of-four (TOF) ratio at 5 min (mean difference MD = 9.28, 95% CI: 4-14.57,
= 66%). However, neither significant reduction in PORC at 10 min (OR = 0.41, 95% CI: 0.15-1.09,
= 0%) nor a better TOF ratio was associated with coadministration of calcium (MD = 0.40, 95% CI: -1.3-2.11). Coadministration of calcium along with neostigmine during the early period of neuromuscular blockade reversal can be used to enhance neuromuscular recovery.
Background: The rising geriatric population is facing significant health and social problems in the developing world that are impacting the quality of their lives. Objective: The study describes the ...general health status and the socioeconomic characteristics of the elderly people of Pakhribas village development committee (VDC) of Eastern Nepal. Materials and Methods: Descriptive cross-sectional study was carried out targeting the people aged 60 years and above in the sample area using a semi-structured questionnaire and convenient sampling to get the required sample size. A total of 189 elderly people who consented were interviewed in May 2010. Result: The major part of the elderly population was in the age group of 60-69 years. Seventy-two percent were illiterate and 75% were still earning with the majority involved in farming. Nine out of ten were living with their families and still made decisions for the household, Eighty-two percent did not feel lonely and 88.4% did not report any misbehavior by the house members. Regarding health, 69% had some diagnosed health issue with 36% suffering from gastritis and 20.4% from chronic lung disease. Using the ICD 10 criteria, depression was found among 18%. The most prevalent geriatric problem was a dental problem as found in 61% even though 87% claimed to brush their teeth regularly. More than half were suffering from visual difficulty and the proportions suffering from memory and hearing issues were also substantive. Smoking habit was found in 60%, and the relation between smoking and chronic respiratory diseases had a statistical association (P = <0.05). The geriatric cases who were misbehaved with felt depressed or neglected in the family (P = <0.0001). Conclusions: The results of the study show that employment, family support, and pension schemes have a positive impact on the social status of the elderly. Health screening clinics should be established in the community to detect health-related disorders. Elderly populations need health education to emphasize the importance of personal and dental hygiene and to abstain from smoking and alcohol.
This meta-analysis aims to comprehensively assess the efficacy and safety of both patent ductus arteriosus (PDA) stents and surgical aortopulmonary shunt (APS) as the initial palliative measures in ...babies relying on ductal-dependent circulation. This review is essential to compare the outcome of relatively newer catheter-based PDA stent procedure with a surgical APS. By synthesizing existing literature, this review aims to provide insights to inform clinical practice and enhance patient care in this challenging clinical scenario. The methodology involved an extensive search of PubMed and Embase databases using specific keywords and terminology related to mortality, procedural outcomes, and postprocedural complications following PDA stent and APS in cyanotic congenital heart defects (CHD) patients. Six retrospective observational studies met the criteria, with 757 patients included. The analysis showed comparable mortality rates between PDA stents and APS. However, PDA stents were associated with decreased risks of mechanical circulatory support, postprocedural complications, and shorter hospital stays, mechanical ventilation, and intensive care unit stays compared to APS. Notably, patients with pulmonary atresia scheduled for biventricular surgery were more prevalent among those receiving PDA stents. In conclusion, while the risk of mortality is similar between PDA stents and APS, PDA stents offer advantages such as shorter hospital stays and reduced complications. Patient characteristics also vary, with a higher prevalence of intact ventricular septum among those receiving PDA stents.
Cytochrome P450 2D6 (CYP2D6) is primarily expressed in the liver and in the central nervous system. It is known to be highly polymorphic in nature. It metabolizes several endogenous substrates such ...as anandamide (AEA). Concomitantly, it is involved in phase 1 metabolism of several antidepressants, antipsychotics, and other drugs. Research in the field of phytocannabinoids (pCBs) has recently accelerated owing to their legalization and increasing medicinal use for pain and inflammation. The primary component of cannabis is THC, which is well-known for its psychotropic effects. Since CYP2D6 is an important brain and liver P450 and is known to be inhibited by CBD, we investigated the interactions of four important highly prevalent CYP2D6 polymorphisms with selected phytocannabinoids (CBD, THC, CBDV, THCV, CBN, CBG, CBC, β-carophyllene) that are rapidly gaining popularity. We show that there is differential binding of CYP2D6*17 to pCBs as compared to WT CYP2D6. We also perform a more detailed comparison of WT and *17 CYP2D6, which reveals the possible regulation of AEA metabolism by CBD. Furthermore, we use molecular dynamics to delineate the mechanism of this binding, inhibition, and regulation. Taken together, we have found that the interactions of CYP2D6 with pCBs vary by polymorphism and by specific pCB class.
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