Conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities: a scoping review.

Introduction: To examine the scope of existing literature on the conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities. Methods: A protocol was developed based on the Joanna Briggs Institute (JBI) scoping review method. MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and EBSCOhost CINAHL, were searched. Results: Eight studies were selected for inclusion; four used quantitative methodology, and four used qualitative methods. Compassion was not defined a priori or a posteriori in any of the included studies. The concept of self-compassion was explicitly defined only for parents of youth with childhood-onset disabilities in three studies a priori. The most reported outcome measure was self-compassion in parents of youth with childhood-onset disabilities. Self-compassion among parents was associated with greater quality of life and resiliency and lower stress, depression, shame and guilt. Discussion: There is limited evidence on the conceptualization, use, and outcomes associated with compassion among youth with childhood-onset disabilities. Self-compassion may be an effective internal coping process among parents of youth with childhood-onset disabilities. Further research is required to understand the meaning of compassion to youth with childhood-onset disabilities, their parents and caregivers. Systematic review registration: https://doi.org/10.17605/OSF.IO/2GRB4.

Association of Inflammatory Markers With Disease Progression and the Severity of COVID-19.

Introduction In December 2019, there was a massive outbreak of viral pneumonia, which had a high case fatality rate. Genetic sequencing of the virus showed similarity with severe acute respiratory syndrome coronavirus (SARS-CoV). It was later named novel coronavirus 2019 while the disease it caused was given the nomenclature of COVID-19. This deadly pneumonia outbreak was declared a pandemic by the World Health Organization (WHO). Aim To derive the strength of the correlation between blood levels of various inflammatory markers with the severity of COVID-19 pneumonia in patients affected with novel coronavirus 2019. Materials and methodology A prospective study was conducted on 300 confirmed cases of COVID-19 infection from August 2020 to July 2021 in SSG Hospital, Vadodara. Diagnosis of patients as confirmed cases of COVID-19 infection was done according to the WHO interim guidance for COVID-19. Their inflammatory markers were done for this study. All COVID-19-positive patients who had given negative consent for enrollment were excluded from the study. Patients were classified based on the severity of acute respiratory distress syndrome (ARDS). Comprehensive medical record information, encompassing biodata, clinical symptoms, comorbidities, and laboratory investigations, was systematically collected. Patients were given the standard treatment protocol as per guidelines. Patients were subjected to detailed investigations comprising complete blood counts and inflammatory markers like C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer. Patients were further investigated by chest X-ray (posteroanterior view) or high-resolution computed tomography of the thorax. Results A total of 300 confirmed cases of COVID-19 infection were included in this study. Most of them were males (52%) with a mean age of 51 years and 48% were females with a mean age of 55 years. The majority of patients (40%) did not have ARDS, 23.3% of patients had mild, 16.7% of patients had moderate, and 20% of patients had severe ARDS. Higher CRP levels, serum ferritin, and serum D-dimer were significantly associated with the severity of COVID-19 infection as compared to those having no symptoms (p < 0.05). Increased levels were associated with severe clinical manifestations of COVID-19. The sensitivity of CRP is 69% and specificity is 100% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of ferritin is 88% and specificity is 81% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of D-dimer is 94% and specificity is 89% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of LDH is 93% and specificity is 84% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. Conclusions Current evidence from our study showed that higher levels of inflammatory markers such as CRP, LDH, D-dimer, and ferritin are associated with the severity of COVID-19 in terms of ARDS and thus could be used as significant prognostic factors of the disease. These indicators might support clinical decisions to identify high fatality cases and poor diagnosis in the initial admission phase.

More than just double discrimination: a scoping review of the experiences and impact of ableism and racism in employment.

PURPOSE: Research has shed light on the employment barriers faced by individuals with disabilities, and by racialized people. The challenges faced by people belonging to both marginalized groups are less well-understood. The purpose of this scoping review was to examine existing research on labour market and workplace experiences of racialized people with disabilities, and to identify how ableism and racism intersect to shape employment experiences and outcomes. METHODS: Seven international databases were searched, covering the period from 2000 to April 2022. Four reviewers independently conducted the screening, and data extraction and analysis were performed on 44 articles that met our inclusion criteria. RESULTS: The findings highlighted rates of workplace ableism and racism (including discrimination allegations and perceived discrimination); types and forms of experiences arising from the intersection of ableism and racism (including unique individual stereotyping and systemic and institutional discrimination); and the role of other demographic variables. The intersection of ableism and racism impacted labour market outcomes, well-being in the workplace, and career/professional advancement. CONCLUSIONS: Our review highlights the need for greater in-depth research focusing explicitly on the intersection of ableism and racism (and of other forms of discrimination), to better understand and address the barriers that racialized people with disabilities face in employment.IMPLICATIONS FOR REHABILITATIONThe experiences of racialized people with disabilities have been under explored, and clinicians and rehabilitation specialists should consider incorporating intersectionality into their practices to better understand and serve these populations.Ableism and racism do not operate in isolation, and clinicians and other professionals need to be aware that racialized people with disabilities may face unique challenges and barriers as a result.Service providers should aim to address gaps and inequities in services faced by racialized people with disabilities which may prevent them from finding and/or maintaining meaningful employment.

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas' tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.

Herpes Simplex Virus Esophagitis in an Immunocompetent Patient.

Esophagitis due to herpes simplex virus (HSV) infection is a rare entity in the immunocompetent population. It is usually seen in immunocompromised hosts, those with human immunodeficiency virus (HIV) infection, malignancies, and patients on immunosuppressive medications. We present a case of a young immunocompetent man with anabolic steroid use who presented with esophagitis symptoms found to be from HSV infection. So far, the use of corticosteroids has been reported as a predisposing factor for HSV esophagitis in immunocompetent hosts in multiple case reports. However, our case suspects that transient immunosuppression with similar medication can cause HSV esophagitis in otherwise immunocompetent hosts.

Crystal structure of Synechococcus phycocyanin: implications of light-harvesting and antioxidant properties.

Phycobiliproteins is a family of chromophore-containing proteins having light-harvesting and antioxidant capacity. The phycocyanin (PC) is a brilliant blue coloured phycobiliprotein, found in rod structure of phycobilisome and has been widely studied for their therapeutic and fluorescent properties. In the present study, the hexameric assembly structure of phycocyanin (Syn-PC) from Synechococcus Sp. R42DM is characterized by X-ray crystallography to understand its light-harvesting and antioxidant properties. The crystal structure of Syn-PC is solved with 2.15 Å resolution and crystallographic R-factors, Rwork/Rfree, 0.16/0.21. The hexamer of Syn-PC is formed by heterodimer of two polypeptide chains, namely, α- and ß-subunits. The structure is analysed at atomic level to reveal the chromophore microenvironment and possible light energy transfer mechanism in Syn-PC. The chromophore arrangement in hexamer, deviation angle and distance between the chromophore contribute to the energy transfer efficiency of protein. The structural attributes responsible for the antioxidant potential of Syn-PC are recognized and annotated on its 3-dimensional structure. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03665-1.

Ableism among children and youth with acquired brain injury and their caregivers: a systematic review.

PURPOSE: Children and youth with acquired brain injury (ABI) experience persistent discrimination and ableism. The purpose of this systematic review was to understand the experiences and impact of ableism among children and youth with ABI. METHOD: Six international databases were systematically searched for articles from 2002-2022. Studies were screened independently by four researchers who performed the data extraction. Study quality was appraised using the Standard quality assessment criteria for evaluating primary research. RESULTS: Of the 2085 studies identified in the search, 15 met the inclusion criteria, which involved 1442 children and youth with brain injuries or caregivers representing them. Studies in the review showed the following key trends: (1) incidence of ableism among children and youth with ABI; (2) experiences of ableism at the individual and institutional levels, (3) impact of ableism (i.e., mental health, social relationships, quality of life) and (4) coping strategies (i.e., resources, supports). CONCLUSIONS: Our findings reveal the alarming incidence of ableism among youth with ABI. Therefore, there is a critical need for more research to explore youth's lived experiences of ableism, especially from their perspectives along with the co-development of solutions to help enhance their social inclusion and well-being.

To Cross the Cervicothoracic Junction? Terminating Posterior Cervical Fusion Constructs Proximal to the Cervicothoracic Junction Does Not Impart Increased Risk of Reoperation in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To evaluate the effect of caudal instrumentation level on revision rates following posterior cervical laminectomy and fusion. METHODS: A retrospective review of a prospectively collected database was performed. Minimum follow-up was one year. Patients were divided into two groups based on the caudal level of their index fusion construct (Group 1-cervical and Group 2- thoracic). Reoperation rates were compared between the two groups, and preoperative demographics and radiographic parameters were compared between patients who required revision and those who did not. Multivariate binomial regression analysis was performed to determine independent risk factors for revision surgery. RESULTS: One hundred thirty-seven (137/204) patients received fusion constructs that terminated at C7 (Group 1), while 67 (67/204) received fusion constructs that terminated at T1 or T2 (Group 2). The revision rate was 8.33% in the combined cohort, 7.3% in Group 1, and 10.4% in Group 2. There was no significant difference in revision rates between the 2 groups (P = .43). Multivariate regression analysis did not identify any independent risk factors for revision surgery. CONCLUSION: This study shows no evidence of increased risk of revision in patients with fusion constructs terminating in the cervical spine when compared to patients with constructs crossing the cervicothoracic junction. These findings support terminating the fusion construct proximal to the cervicothoracic junction when indicated. LEVEL OF EVIDENCE: III.

Crystal structure analysis of phycoerythrin from marine cyanobacterium Halomicronema.

Phycoerythrin (PE) is green light-absorbing pigment-protein that assists in efficient light harvesting in cyanobacteria and red-algae. PE in cyanobacteria stays less studied so far as compared to that in red algae. In this study, PE from marine cyanobacteria Halomicronema sp. R31DM is purified and subjected for its structural characterisation by X-ray crystallography in order to understand its light-harvesting characteristics. The crystal structure is solved to a resolution-limit of 2.21 Å with reasonable R-factors values, 0.16/0.21 (Rwork/ Rfree). PE forms hexamer of hetero-dimers made up of two peptide chains, α- and ß-subunits containing 2 and 3 phycoerythrobilin (PEB) chromophores covalently attached to them, respectively. Geometry of five chromophores is analysed along with their relative position within the PE hexamer. Also, their interactions with the surrounding microenvironment are analysed. The plausible energy transfer pathways in hexamer structure have been predicted based on relative position and geometry of chromophores. This structure enriches the structural information of cyanobacterial PE in order to understand its light-harvesting capacity.Communicated by Ramaswamy H. Sarma.

A Review on Recent Development of Novel Heterocycles as Acetylcholinesterase Inhibitor for the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturallyderived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 µm using Ellman's in vitro AChE assay method and show high BBB permeability in vitro. In addition, the in vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced ß-amyloid (Aß) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer's disease.

Exploring the structural aspects and therapeutic perspectives of cyanobacterial phycobiliproteins.

Phycobiliproteins (PBPs) of cyanobacteria and algae possess unique light harvesting capacity which expand the photosynthetically active region (PAR) and allow them to thrive in extreme niches where higher plants cannot. PBPs of cyanobacteria/algae vary in abundance, types, amino acid composition and in structure as a function of species and the habitat that they grow in. In the present review, the key aspects of structure, stability, and spectral properties of PBPs, and their correlation with ecological niche of cyanobacteria are discussed. Besides their role in light-harvesting, PBPs possess antioxidant, anti-aging, neuroprotective, hepatoprotective and anti-inflammatory properties, which can be used in therapeutics. Recent developments in therapeutic applications of PBPs are reviewed with special focus on 'route of PBPs administration' and 'therapeutic potential of PBP-derived peptide and chromophores'.

In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine derivatives by Mechanochemistry Approach for Targeting Human Neutrophil Elastase against Lung Cancer.

BACKGROUND: Pyrimidine derivative has evinced its biological importance in targeting lung cancer by inhibiting neutrophil elastase. METHODS: All THPM derivatives were synthesized by the grindstone method at ambient temperature followed by molecular docking study for efficient binding interaction of THPM compounds by targeting human neutrophil elastase (HNE) (PDB ID: 5A0A) and In-silico ADMET study using PkCSM. Moreover, all synthesized compounds were characterized by spectroscopy techniques and screened for anti-cancer activity using in vitro HNE assay kit. RESULTS: We reported a one-pot solvent-free mechanochemical approach for synthesizing tetrahydropyrimidine (THPM) derivatives from various aromatic aldehydes, ethyl cyanoacetate, and urea followed by in silico study and evaluation against human neutrophil elastase (HNE) for treatment of lung cancer. We calibrated the best molecules that bound to specific targets more efficiently using a molecular docking approach and provided the desired efficacy. In-silico ADMET studies revealed that all best-scored compounds had drug-like characteristics for potential use as human neutrophil elastase inhibitors (HNE) in lung cancer treatment. Additionally, the in vitro studies revealed that compounds 1, 2, and 8 show potent HNE inhibitory activity for lung cancer treatment. CONCLUSION: In a nutshell, the tetrahydropyrimidine (THPM) scaffold and its derivatives may serve as potential HNE inhibitors for the development of a promising anti-cancer agent.

Recent Update on the Development of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors: A Promising Target for the Treatment of Parkinson's Disease.

Parkinson's disease is a relatively common neurological disorder with incidence increasing with age. Since current medications only relieve the symptoms and do not change the course of the disease, therefore, finding disease-modifying therapies is a critical unmet medical need. However, significant progress in understanding how genetics underpins Parkinson's disease (PD) has opened up new opportunities for understanding disease pathogenesis and identifying possible therapeutic targets. One such target is leucine-rich repeat kinase 2 (LRRK2), an elusive enzyme implicated in both familial and idiopathic PD risk. As a result, both academia and industry have promoted the development of potent and selective inhibitors of LRRK2. In this review, we have summarized recent progress in the discovery and development of LRKK2 inhibitors as well as the bioactivity of several small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or in vivo.

Therapeutic potential of bioactive compounds from Punica granatum extracts against aging and complicity of FOXO orthologue DAF-16 in Caenorhabditis elegans.

Some natural fruits have significant importance in improving health which provides many nutritional supplements essential to maintain proper metabolism with the age. In this study, phytochemical screening of extract (methanolic) of Punica granatum arils, outer and inner peels was confirmed by the respective spot tests. Quantification of phytochemical constituents revealed the plentiful of total phenols in the outer peels in comparison to inner peels and juice whereas total flavonoids and vitamin C are abundant in inner peel and juice, respectively. High-performance liquid chromatography, Gas chromatography along with mass spectrometry and Fourier-transform infrared spectroscopy analysis revealed the presence of compound 9, 17-octadecadienal, (Z) in the outer/inner peels. A compound N-hexadecanoic acid was also observed in the outer peels. Extracts from every section of the fruits were comprehensively evaluated for their antioxidant activity. Contrary to fruit aril juice, the extracts of outer and inner peels exhibited significant and dose-dependent in vitro antioxidant and radical-scavenging potentials. The supplementation of P. granatum extracts (PGEs) significantly enhanced the lifespan of C. elegans. The protective effect of PGEs was also observed against oxidative stress in C. elegans. Additionally, the involvement of FOXO orthologue DAF-16 dependent longevity was obtained with PGEs (outer peel and inner peel) fed TJ356 worms. Overall, the results indicate the vital role of PGEs especially the extracts of outer peels in life-saving mechanisms of C. elegans by virtue of their antioxidant asset and life-prolonging effects via daf-16 dependent Insulin signaling pathway. See also Figure 1(Fig. 1).

Extension of life span and stress tolerance modulated by DAF-16 in Caenorhabditis elegans under the treatment of Moringa oleifera extract.

The present study was focused to isolate the bioactive compounds present in the leaves of Moringa oleifera which contains a high nutritional value. Furthermore, the research was aimed to evaluate the antioxidant, anti-aging, and anti-neurodegenerative properties of M. oleifera using the experimental model Caenorhabditis elegans. The separation of compounds from the crude extract and its identification was carried out through TLC, Column chromatography, UV absorption spectroscopy, and GC-MS. The compounds identified in most abundant fraction of column chromatography were [Phenol-2,4-bis(1,1-dimethylethyl)- phosphite (3:1)] and Tetratetracontane. The result suggests that the leaves extracts and column fraction were able to significantly extend the life span of the N2 wild-type strain of C. elegans. The most potent life span extending effect was displayed by the dichloromethane extract of leaves which was 21.73 ± 0.142 days compared to the control (16.55 ± 0.02 days). It could also extend the health span through improved physiological functions such as pharyngeal pumping, body bending, and reversal frequency with increased age. The treated worms were also exhibited improved resistance to thermal stress, oxidative stress, and reduced intracellular ROS accumulation. Moreover, the leaves extract could elicit neuroprotection as it could delay the paralysis in the transgenic strain of C. elegans 'CL4176' integrated with Aß. Interestingly, The RNAi experiment demonstrated that the extended life span under the treatment of extracts and the compound was daf-16 dependent. In transgenic C. elegans TJ356, the DAF-16 transcription factor was localized in the nucleus under the stress conditions, further supported the involvement of the daf-16 gene in longevity. Overall, the study suggests the potential of M. oleifera as a dietary supplement and alternative medicine to defend against oxidative stress and aging.

Cyanobacterial pigment protein allophycocyanin exhibits longevity and reduces Aß-mediated paralysis in C. elegans: complicity of FOXO and NRF2 ortholog DAF-16 and SKN-1.

The allophycocyanin (APC) protein purified from Phormidium sp. A09DM was investigated for its in vivo antioxidant and anti-aging potential in Caenorhabditis elegans. An increased mean lifespan of APC-treated (100 µg/ml) worms (wild type) were observed from 16 ± 0.2 days (control) to 20 ± 0.1 days (treated). APC-treated worms also showed improved physiological marker of aging such as the rate of pharyngeal pumping and higher rate of survival against oxidative and thermal stress. Furthermore, APC was found to moderate the expression of human amyloid beta (Aß1-42) as well as associated Aß-induced paralysis in the transgenic C. elegans CL4176 upon increase in temperature. Furthermore, RNA interference (RNAi)-mediated studies revealed the dependence of downstream regulator daf-16, independent of stress-induced resistance gene skn-1 in the APC treated C. elegans. In the present study, we tried to demonstrate the anti-aging activity, longevity and protective effects of APC against cellular stress in C. elegans, which can lead to the use of this biomolecule in drug development for age-related disorders.

Carcinoid Tumor: Advances in Treatment Options.

Small bowel neoplasms are rare, accounting for only 3%-6% of all gastrointestinal neoplasms. Carcinoid tumors represent a large portion of these (20%-30%), making them the second most common small bowel malignancy after adenocarcinoma. Gastrointestinal carcinoids constitute 70% of all neuroendocrine tumors, and out of those, 42% originate in the small bowel. They are predominantly seen in older patients around the age of 65 years. From 1973 to 2004, there has been more than a fourfold increase in the incidence of carcinoid tumors. This can be probably due to increased diagnostic accuracy rather than an actual increase in the number of new cases. The workup of a suspicious case of gastrointestinal bleeding consists of esophagogastroduodenoscopy and/or colonoscopy, and other imaging tests including video capsule endoscopy and balloon-assisted endoscopy. Management of the tumors is dependent on the size and location of the lesion. Treatment options include surgery, endoscopic removal of tumors, and various immunotherapy and chemotherapeutic agents.

Comparison of abacavir-specific effector and proliferating functions of CD8 T cells in abacavir-treated HIV-1 patients.

Susceptibility to abacavir hypersensitivity (ABH) in HIV-1-positive patients is strongly linked to the carriage of HLA-B*57:01 and the potential mechanism includes drug-specific activation of cytokine producing CD8 T cells exclusively in individuals carrying HLA-B*57:01. Here, we report a detailed characterization of abacavir-induced functional response of CD8 T cells in HLA-B*57:01pos individuals. Peripheral blood mononuclear cells (PBMNCs) from HLA-B*57:01pos ABHpos and HLA-B*57:01neg ABHneg individuals were stimulated with abacavir. Multicolor flow cytometry was performed to assess the cytokine (IFNγ) production and degranulation (CD107a expression) after 6-18 hr culture and to enumerate proliferating CD4/CD8 T cells by culturing carboxyfluorescein diacetate succinimidyl ester-loaded PBMNCs for 7 days. CD8 T cells from HLA-B*57:01pos ABHpos individuals were multifunctional: proliferating, IFNγ producing, degranulating (CD107apos ), and both degranulating and IFNγ producing (CD107apos IFNγpos ). Degranulating CD8 T cells in general and both degranulating and IFNγ producing CD8 T cells in particular dominated abacavir-specific immune response. All functional responses were partially blocked by addition of HLA-B*57:01-reactive Bw4 mAb, but not by non-HLA-B*57:01-reactive Bw6 mAb. In conclusion, the study demonstrates that abacavir-specific CD8 T-cell-restricted immune response in HLA-B*57:01pos ABHpos HIV-1 patients has multiple effector and proliferating functions, where the primary effector response appears to be the release of cytolytic granules. The findings have implications for immunotherapy of HLA-related drug hypersensitivities.

Phylogenetic and crystallographic analysis of Nostoc phycocyanin having blue-shifted spectral properties.

The distinct sequence feature and spectral blue-shift (~10 nm) of phycocyanin, isolated from Nostoc sp. R76DM (N-PC), were investigated by phylogenetic and crystallographic analyses. Twelve conserved substitutions in N-PC sequence were found distributed unequally among α- and ß-subunit (3 in α- and 9 in ß-subunit). The phylogenetic analysis suggested that molecular evolution of α- and ß-subunit of Nostoc-phycocyanin is faster than evolution of Nostoc-species. The divergence events seem to have occurred more frequently in ß-subunit, compared to α-subunit (relative divergence, 7.38 for α-subunit and 9.66 for ß-subunit). Crystal structure of N-PC was solved at 2.35 Å resolution to reasonable R-factors (Rwork/RFree = 0.199/0.248). Substitutions congregate near interface of two αß-monomer in N-PC trimer and are of compensatory nature. Six of the substitutions in ß-subunit may be involved in maintaining topology of ß-subunit, one in inter-monomer interaction and one in interaction with linker-protein. The ß153Cys-attached chromophore adopts high-energy conformational state resulting due to reduced coplanarity of B- and C-pyrrole rings. Distortion in chromophore conformation can result in blue-shift in N-PC spectral properties. N-PC showed significant in-vitro and in-vivo antioxidant activity comparable with other phycocyanin. Since Nostoc-species constitute a distinct phylogenetic clade, the present structure would provide a better template to build a model for phycocyanins of these species.

Therapeutic potential of cyanobacterial pigment protein phycoerythrin: in silico and in vitro study of BACE1 interaction and in vivo Aß reduction.

Cyanobacteria are an immense source of innovative classes of pharmacologically active compounds exhibiting various biological activities ranging from antioxidants, antibiotics, anticancer, anti-inflammatory to anti-Alzheimer's disease. In the present study, we primarily targeted the inhibition of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) by a naturally occurring cyanobacterial protein phycoerythrin (C-PE). BACE1 cleaves amyloid-ß precursor protein (APP) and leads to accumulation of neurotoxic amyloid beta (Aß) plaques in the brain, as an attribute of Alzheimer's disease (AD). Inhibition of BACE1 was measured in terms of their association and dissociation rate constants, thermodynamics of binding using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The kinetic parameters for enzyme activity were also measured using synthetic decapeptide as a substrate. We further validated the potential of PE by in-vivo histopathological staining of Aß aggregate mutant Caenorhabditis elegans CL4176 by Thioflavin-T. The present studies pave the way for the application of naturally occurring C-PE as a putative therapeutic drug for the AD.