2D-QSAR, molecular docking and MD simulation based virtual screening of the herbal molecules against Alzheimer's disorder: an approach to predict CNS activity.

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimer's Disorder (AD). Numerous reports in the literature predict and demonstrate in-vitro, and in-silico anticholinergic activity of herbal molecules, however, majority of them failed to find clinical application. To address these issues, we developed a 2D-QSAR model that could efficiently predict the AChE inhibitory activity of herbal molecules along with predicting their potential to cross the blood-brain-barrier (BBB) to exert their beneficial effects during AD. Virtual screening of the herbal molecules was performed and amentoflavone, asiaticoside, astaxanthin, bahouside, biapigenin, glycyrrhizin, hyperforin, hypericin, and tocopherol were predicted as the most promising herbal molecules for inhibiting AChE. Results were validated through molecular docking, atomistic molecular dynamics simulations and Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) studies against human AChE (PDB ID: 4EY7). To determine whether or not these molecules can cross BBB to inhibit AChE within the central nervous system (CNS) for being beneficial for the management of AD, we determined a CNS Multi-parameter Optimization (MPO) score, which was found in the range of 1 to 3.76. Overall, the best results were observed for amentoflavone and our results demonstrated a PIC50 value of 7.377 nM, molecular docking score of -11.5 kcal/mol, and CNS MPO score of 3.76. In conclusion, we successfully developed a reliable and efficient 2D-QSAR model and predicted amentoflavone to be the most promising molecule that could inhibit human AChE enzyme within the CNS and could prove beneficial for the management of AD.Communicated by Ramaswamy H. Sarma.

Feasibility of group telerehabilitation for individuals with chronic acquired brain injury: integrating clinical care and research.

BACKGROUND: Acquired brain injury (ABI) is a leading cause of lifelong disability, but access to treatment in the chronic stages has significant barriers. Group-based, remotely delivered neurorehabilitation reduces costs, travel barriers, and infection risk; however, its feasibility for patients with ABI is not well-established. OBJECTIVES: To investigate the feasibility of remotely group-based cognitive and mood therapies for persons with chronic ABI. METHODS: Three hundred and eighty-eight adults with chronic ABI participated in group tele-neurorehabilitation modules comprising Cognitive Behavioral Therapy, Goal Management Training®, Relaxation and Mindfulness Skills Training, and/or a novel Concussion Education & Symptom Management program. Assessments comprised quantitative metrics, surveys, as well as qualitative semi-structured interviews in a subset of participants. RESULTS: High retention, adherence, and satisfaction were observed. Facilitators of treatment included accessibility, cost-effectiveness, and convenience. Adoption of technology was high, but other people's technological interruptions were a barrier. Self-reported benefits specific to group-based format included improved mood, stress management, coping, interpersonal relationships, cognitive functioning, and present-mindedness. CONCLUSIONS: The present study examined chronic ABI patients' perceptions of telerehabilitation. Patients found remotely delivered, group-based mood, and cognitive interventions feasible with easy technology adoption. Group format was considered a benefit. Recommendations are provided to inform design of remotely delivered ABI programs.

Group-based mood and cognitive telerehabilitation is feasible for persons with chronic acquired brain injury, with high reported satisfaction.Screening for technical proficiency and providing ongoing technical support improves therapy adherence and retention.Integration of clinical care and research is feasible for delivering remote therapies to persons with brain injury.

Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit Spike Protein of SARS-CoV-2 Binding to ACE2 Receptor: In Silico Approach.

COVID-19, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and neutrapilin-1 receptors. Since Chloroquine has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and artemisinin for its interaction with spike proteins (6VXX, 6VYB) and its variant 7NXA, respectively. Molecular docking study of phytocompounds and SARS-CoV-2 spike protein was performed by using AutoDock/Vina software. Molecular dynamics (MD) simulation was performed for 50ns. Among all the phytocompounds, molecular docking studies revealed lowest binding energy of artemisinin with 6VXX and 6VYB, with Etotal -10.5 KJ mol-1 and -10.3 KJ mol-1 respectively. Emodin showed the best binding affinity with 6VYB with Etotal -8.8 KJ mol-1and SARS-CoV-2 B.1.351 variant (7NXA) with binding energy of -6.4KJ mol-1. Emodin showed best interactions with TMPRSS 2 and ACE2 with Etotal of -7.1 and -7.3 KJ mol-1 respectively, whereas artemisinin interacts with TMPRSS 2 and ACE2 with Etotal of -6.9 and -7.4 KJ mol-1 respectively. All the phytocompounds were non-toxic and non-carcinogenic. MD simulation showed that artemisinin has more stable interaction with 6VYB as compared to 6VXX, and hence proposed as potential phytochemical to prevent SARS-CoV-2 interaction with ACE-2 receptor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40495-021-00259-4.

The efficacy of anti-inflammatory treatment interventions on depression in individuals with major depressive disorder and high levels of inflammation: A systematic review of randomized clinical trials.

BACKGROUND: Studies evaluating the efficacy of anti-inflammatory treatment strategies for major depressive disorder (MDD) commonly include participants who do not demonstrate elevated concentrations of baseline inflammatory mediators, or simply fail to assess baseline inflammation. This may result in an underestimation of the efficacy of such treatment strategies. SAMPLING AND METHODS: This systematic review included randomized controlled trials related to the use of anti-inflammatory treatment strategies in individuals who demonstrate elevated concentrations of inflammatory mediators, identified by searching OVID MEDLINE, OVID EMBASE, and OVID PsychINFO. RESULTS: Fifty-one randomized controlled trials were identified via a title and abstract screen, of which 43 were excluded following full-text screening. Of the 8 included trials (n = 437), 5 utilized anti-inflammatory pharmaceuticals, 2 utilized omega-3 fatty acids, and 1 utilized exercise and meditation. Among these studies, only the trial related to exercise and meditation demonstrated both an elevation in baseline inflammation, and a significant reduction in inflammation following intervention. Issues related to insufficient interventions and/or lack of reporting of inflammatory mediators at one or more time-points were common. CONCLUSION: Among the growing number of studies which examine the potential antidepressant benefit of anti-inflammatory treatment strategies, few have studied populations which demonstrate elevated baseline concentrations. Further, studies commonly fail to induce significant changes in inflammation following intervention. Together, this may explain the low efficacy frequently reported with such interventions. Future studies which utilize both stronger interventions (sufficient to reduce levels of inflammation), and participants with elevated baseline concentrations, may produce a more substantial influence on symptoms of (MDD).

Branched Chain Amino Acids (BCAAs) and Traumatic Brain Injury: A Systematic Review.

BACKGROUND: Despite the prevalence of traumatic brain injury (TBI), pharmaceutical treatment options for brain injury remain limited. However, nutritional intervention (such as with branched chain amino acids [BCAAs]) has emerged as a promising treatment option for TBI. OBJECTIVES: (1) To determine whether TBI patients have lower levels of endogenous BCAAs postinjury; and (2) to evaluate whether post-TBI BCAA supplementation improves clinical outcome. DESIGN: A systematic review of primary research articles examining the relationship between BCAAs and TBI recovery indexed in Ovid/MEDLINE, EMBASE, and PsycINFO. RESULTS: Of the 11 studies identified, 3 examined the effects of TBI on endogenous BCAA levels and consistently reported that BCAA concentrations were depressed postinjury. The remaining 8 studies examined the effects of BCAA supplementation on TBI outcome in animals (n = 3) and humans (n = 5). The animal studies (in mild-to-moderate TBI) showed that BCAAs improved post-TBI outcome. Similar results were found in human trials (conducted primarily in patients with severe TBI), with 4 of the 5 studies reporting improved outcome with BCAA supplementation. CONCLUSION: Although our review demonstrates an overall positive association between BCAAs and TBI outcome, the evidence of the efficacy of supplementation has been limited to severe TBI. To date, there is insufficient evidence to determine the benefits of BCAAs in mild TBI. Given the high frequency of mild TBI and the promise of BCAAs as an intervention in severe TBI, future research should examine the effects of BCAAs in milder brain injury.

A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion.

BACKGROUND: Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. OBJECTIVE: Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). METHODS: A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. RESULTS: The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post-TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. CONCLUSION: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.

Blood conservation in neurosurgery: erythropoietin and autologous donation.

BACKGROUND: Neurosurgery may involve significant blood loss and frequently requires allogeneic red blood cell (RBC) transfusion. Preoperative recombinant erythropoietin (EPO) may be used to improve erythroid status and recovery, and used either alone or in combination with preoperative autologous donation (PAD) it may reduce exposure to allogeneic RBC. We wished to study the use of EPO with and without PAD and the risk of RBC transfusion in neurosurgery. METHODS: Using a retrospective case-control design, 57 patients who received EPO preoperatively were matched 2:1 for age, sex, year of surgery, and International Classification of Diseases code most responsible for surgery (three were excluded because of stringent matching criteria, leaving 54 cases and 108 comparison subjects). Thirty-two cases participated in PAD. Medical and anesthetic records as well as laboratory investigations were reviewed and extracted. RESULTS: Allogeneic RBC exposure was identical for EPO cases and comparison subjects (18.5%). Concomitant PAD and EPO did not reduce allogeneic RBC exposure (21.9%), and resulted in a greater number of RBC units transfused. Last recorded hemoglobin levels suggested that autologous RBCs were not more liberally used. Patients who engaged in PAD and EPO suffered from iatrogenic anemia. A significant proportion (58.6%) of the autologous RBCs was ultimately not used and discarded. CONCLUSION: Further research is needed to determine the efficacy of EPO in neurological surgery. PAD does not appear to reduce the risk of allogeneic RBC transfusion, despite concomitant EPO. Indeed, PAD resulted in iatrogenic anemia and increased transfusion requirements. The cost-effectiveness of blood conservation efforts in neurosurgery deserves additional research.