In-Vitro Evaluation of Anti-Inflammatory and Anti-Microbial Properties of Ethanolic Extract of Cydonia Oblonga Seeds

49-52Phytochemical, antimicrobial, antioxidant and anti-inflammatory properties of ethanol extract of Cydonia oblonga were studied. The antioxidant and anti-inflammatory efficacy of the extract was assessed through different methods using DPPH and bovine albumin respectively. Total phenolic content (TPC) was estimated using Folin-Cioucalteu reagent. Antimicrobial effect of seeds was studied using disc diffusion method against gram positive and negative bacteria viz; S.aureus, P.aeruginosa and fungi C. albicans. Phyto-chemical analysis showed the presence of alkaloids, phenols, tannins, amino acids, carbohydrate, fats/oils and glycosides. TPC of the seed extract was found to be 37.46±0.10 mg GAE/gm, extract also showed significant antioxidant and anti-inflammatory activity with IC50 value of 299.98µg/ml and 300µg/ml respectively. Anti-microbial results indicated that Cydonia oblonga seeds extract is effective against gram positive bacteria

In-Vitro Evaluation of Anti-Inflammatory and Anti-Microbial Properties of Ethanolic Extract of Cydonia Oblonga Seeds

Phytochemical, antimicrobial, antioxidant and anti-inflammatory properties of ethanol extract of Cydonia oblonga were studied. The antioxidant and anti-inflammatory efficacy of the extract was assessed through different methods using DPPH and bovine albumin respectively. Total phenolic content (TPC) was estimated using Folin-Cioucalteu reagent. Antimicrobial effect of seeds was studied using disc diffusion method against gram positive and negative bacteria viz; S.aureus, P.aeruginosa and fungi C. albicans. Phyto-chemical analysis showed the presence of alkaloids, phenols, tannins, amino acids, carbohydrate, fats/oils and glycosides. TPC of the seed extract was found to be 37.46±0.10 mg GAE/gm, extract also showed significant antioxidant and anti-inflammatory activity with IC50 value of 299.98µg/ml and 300µg/ml respectively. Anti-microbial results indicated that Cydonia oblonga seeds extract is effective against gram positive bacteria

A Comparison of quality of life outcomes following different techniques of mastoid surgery

- Background: Mastoid surgery carried out to treat chronic otitis media (COM) can lead to an improvement in objective and subjective measures post-operatively. This study aims to look at the subjective change in quality of life using the Glasgow Benefit Inventory relative to the type of mastoid surgery undertaken. - Method: A retrospective multi-centre postal questionnaire survey of 157 patients who underwent mastoid surgery from 2008-2012. - Results: 83 questionnaire responses were received from patients having the surgery at 3 different hospitals (a response rate of 53%). 57% of patients had a Glasgow benefit Score of 0 indicating no change in quality of life post-operatively. 35% scored +50 indicating a significant improvement. The only significant difference found was that women fare worse after surgery than men. - Conclusions: The choice of mastoid surgery technique should be determined by clinical need and surgeon preference. There is no improvement in quality of life for most patients

Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget’s disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group’s conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02172-5

Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

<p>Abstract</p> <p>Background</p> <p>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features.</p> <p>Methods</p> <p>In 40 cases of invasive breast cancer, BNIP3 mRNA <it>in situ </it>hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry.</p> <p>Results</p> <p>BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells.</p> <p>Conclusion</p> <p>BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response.</p

Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum-derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N297-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N297-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar-depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe