Nonpharmacological methods of pain relief such as acupressure are becoming increasingly popular worldwide. Practitioners often claim that such methods are highly effective and less invasive than analgesic drugs, but available empirical evidence is largely inconclusive. This study aimed to test the hypothesis that, postacupressure intervention, the amount of pain experienced by sampled leukemia patients, who received acupressure in addition to standard care, will reduce substantially compared to patients who received only routine treatment. This controlled trial was undertaken with hospitalized leukemia patients between February and June 2015. Our primary sample consisted of 100 participants who were randomly allocated to 2 groups. One (intervention) group underwent 12 acupressure sessions in addition to standard treatment while the control group received no intervention apart from being given the standard treatment for leukemia. The visual analogue scale was used to measure the levels of pain experienced. No significant differences were found between the 2 groups across 12 interventions. However, each group reported significantly different pain level changes before and after each intervention, suggested that the acupressure method was effective in reducing pain in the short term. Nurses are able to apply this complementary therapy alongside other procedures to manage these patients' pain. It is recommended that further studies be conducted to better understand the specific conditions under which acupressure can provide effective pain relief.
Previous empirical studies have shown that both spiritual well-being (SWB) and death anxiety (DA) significantly affect the mental health of patients with acute diseases. In this regard, our paper contributes to the extant literature by scrutinizing the conditional relationship between SWB and DA as well as the various mechanisms underpinning such a relationship in patients with acute myocardial infraction (AMI). A descriptive, correlational methodology was utilized. Our main sample consisted of 300 patients with acute myocardial infraction who were hospitalized in a specialized medical institution in Iran throughout a two-month period (i.e. August-October 2015). Patients completed Spiritual Well-Being Scale (SWBS) and Templer's Death Anxiety Scale (TDAS). Even though our study showed that the relationship between SWB and DA in patients with AMI is non-significant, we found that (1) single patients with higher SWB have lower DA, (2) single patients with higher SWB as well as social support have significantly lower DA, and (3) for single men/men without social support, there is a negative relationship between SWB and DA. The relationship between SWB and DA is influenced by factors such as sex, marital status and social support. In addition, the specific nature of this relationship (i.e. strength and sign) is dependent upon the sociodemographic characteristics of patients as well as other contextual influences. Result revealed that although relationship between SWB and DA is non-significant, this is influenced by factors such as sex and social support. In addition, the specific nature of this relationship (i.e. strength and sign) is dependent upon the sociodemographic characteristics of patients as well as other contextual influences.
Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.
Hypoxia-inducible factors (HIFs) are transcription factors that regulate erythropoietin (EPO) synthesis and red blood cell (RBC) production. Prolyl-4-hydroxylase domain (PHD) enzymes are key regulators of HIF's stability and activity. Inhibiting PHD enzymes can enhance HIF-mediated responses and have therapeutic potential for diseases such as anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation. In this study, we searched for novel PHD inhibitors from four databases of natural products and synthetic compounds: AfroDb Natural Products, AnalytiCon Discovery Natural Product (NP), HIM-Herbal Ingredients In-Vivo Metabolism, and Herbal Ingredients' Targets, with a total number of 13,597 compounds. We screened the candidate compounds by molecular docking and validated them by molecular dynamics simulations and free energy calculations. We identified four target hits (ZINC36378940, ZINC2005305, ZINC31164438, and ZINC67910437) that showed stronger binding affinity to PHD2 compared to the positive control, Vadadustat (AKB-6548), with docking scores of - 13.34 kcal/mol, - 12.76 kcal/mol, - 11.96 kcal/mol, - 11.41 kcal/mol, and - 9.04 kcal/mol, respectively. The target ligands chelated the active site iron and interacted with key residues (Arg 383, Tyr329, Tyr303) of PHD2, in a similar manner as Vadadustat. Moreover, the dynamic stability-based assessment revealed that they also exhibited stable dynamics and compact trajectories. Then the total binding free energy was calculated for each complex which revealed that the control has a TBE of - 31.26 ± 0.30 kcal/mol, ZINC36378940 reported a TBE of - 38.65 ± 0.51 kcal/mol, for the ZINC31164438 the TBE was - 26.16 ± 0.30 kcal/mol while the ZINC2005305 complex reported electrostatic energy of - 32.75 ± 0.58 kcal/mol. This shows that ZINC36378940 is the best hit than the other and therefore further investigation should be performed for the clinical usage. Our results suggest that these target hits are promising candidates that reserve further in vitro and in vivo validations as potential PHD inhibitors for the treatment of renal anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation.