Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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Identification of B cell epitopes of Per a 5 allergen using bioinformatic approach

BackgroundImmune epitopes of allergens are pivotal for development of novel diagnostic and therapeutic modalities. Present study aims to identify antigenic determinants of Per a 5, a clinically relevant cross reactive cockroach allergen.MethodsThe three dimensional structure of Per a 5 was modelled using Modeller 9v11 software. A combination of sequence and structure based computational tools were employed for predicting B cell epitopes. Epitopes were synthesized and immunoreactivity was assessed by ELISA using cockroach hypersensitive patient’s sera. Cross-reactivity potential of predicted epitopes was assessed with SDAP and ConSurf and validated by IgE ELISA with fungal and mite hypersensitive patient’s sera.ResultsPer a 5 structure exhibited good quality factor in ERRAT and high stereochemical stability. In silico analysis revealed six B cell epitopes (BC-P1 to P6). BC-P3 demonstrated significant IgE binding followed by BC-P2 and BC-P1 with cockroach hypersensitive patient’s sera. Per a 5 epitopes demonstrate considerable similarity with broad spectrum of allergens from fungal, mites, helminths, fruits and nuts. Analysis of PD values indicate BC-P4 to be well conserved among dust mite and helminth GSTs (8.89, 10.63 and 10.69 with D. pteronyssinus, W. bancrofti and F. hepatica respectively). ConSurf analysis of Per a 5 revealed specific enrichment of evolutionarily similar amino acid residues in BC-P2 (with fungal and mite GSTs) and BC-P4 (with mite and helminth GSTs). Further, IgE binding analysis of epitopes demonstrate BC-P2, BC-P3 and BC-P5 as high IgE binders in fungal hypersensitive sera while BC-P1, BC-P2, BC-P4 and BC-P5 demonstrated significant IgE binding with mite hypersensitive sera.ConclusionsAmong the predicted epitopes, BC-P3 demonstrates maximal IgE binding ability. Computational analysis suggests strong evolutionary conservation and cross reactive potential of BC-P4 with allergens in dust mite and helminths. ELISA highlights predictive potential of analysing evolutionarily conserved residues for uncovering potentially cross reactive antigenic determinants.General significanceImmune epitopes of Per a 5 were identified for aiding molecular diagnosis and potential cross reactivity.     

The bane of coastal marine environment: A fatal case of Vibrio vulnificus associated cellulitis and septicaemia

Vibrio vulnificus is a Gram negative motile bacterium known to cause fatal septicaemia and wound infection. It is commonly associated with the consumption of under-cooked seafood or exposure to marine environment. We report a case of a 55 year old male patient, who was presented with right lower limb cellulitis and septicaemia due to V. vulnificus. V. vulnificus infection in India are rare. However, increasing reports of V. vulnificus from India recommends considering the pathogen while dealing necrotising fasciitis especially in the proximity of marine environment.     

Effect of a multi-disciplinary program on anthropometric and biochemical parameters in obese and overweight elementary school girls: A randomized clinical trial

Background and aimsObesity and overweight in children are associated with an increased risk of several health issues. The present study aimed to assess the effects of a multi-disciplinary program (including nutrition education using a smartphone game, physical activity, and cognitive behavioral therapy [CBT]) on the management of obesity and overweight in elementary school girls.Methods and resultsSixty-two school girls above the 85th percentile of body mass index (BMI) for age were randomly assigned to two groups. During 10 weeks of study, the intervention group received a multi-disciplinary intervention, including nutrition education using a smartphone game, aerobic exercise, and CBT. The control group received usual traditional nutritional education. Biochemical and metabolic factors were assessed, including fasting blood sugar (FBS), lipid profile, serum leptin, and anthropometric measurements. The Dutch Eating Behavior Questionnaire (DEBQ) and metabolic equivalent test (MET) were also conducted. The intervention group showed more promising results in weight loss, waist circumference (WC), hip circumference (HC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and FBS compared to the control group (P < 0.05). In addition, MET and DEBQ scores in all three sections of emotions, stimuli, and restriction were better in the intervention group than in the control group (P < 0.05). However, there was no significant difference between groups regarding the results of serum leptin and waist-to-hip ratio (WHR; p > 0.05).ConclusionsThe results indicated that education through smartphone games could possibly affect performance in real life. In addition, the multi-disciplinary approach to childhood obesity might have better performance in most areas than the single-intervention approach in obesity management.     

HIV transmitting mononuclear phagocytes; integrating the old and new

In tissue, mononuclear phagocytes (MNP) are comprised of Langerhans cells, dendritic cells, macrophages and monocyte-derived cells. They are the first immune cells to encounter HIV during transmission and transmit the virus to CD4 T cells as a consequence of their antigen presenting cell function. To understand the role these cells play in transmission, their phenotypic and functional characterisation is important. With advancements in high parameter single cell technologies, new MNPs subsets are continuously being discovered and their definition and classification is in a state of flux. This has important implications for our knowledge of HIV transmission, which requires a deeper understanding to design effective vaccines and better blocking strategies. Here we review the historical research of the role MNPs play in HIV transmission up to the present day and revaluate these studies in the context of our most recent understandings of the MNP system.     

Biologically Active Adrenomedullin (bio-ADM) is of Potential Value in Identifying Congestion and Selecting Patients for Neurohormonal Blockade in Acute Dyspnea

PurposeThis study was designed to evaluate the role of biologically active adrenomedullin (bio-ADM) in congestion assessment and risk stratification in acute dyspnea.MethodsThis is a sub-analysis of the Lithuanian Echocardiography Study of Dyspnea in Acute Settings. Congestion was assessed by means of clinical (peripheral edema, rales) and sonographic (estimated right atrial pressure) parameters. Ninety-day mortality was chosen for outcome analysis.ResultsThere were 1188 patients included. Bio-ADM concentration was higher in patients with peripheral edema at admission (48.2 [28.2-92.6] vs 35.4 [20.9-59.2] ng/L, P < .001). There was a stepwise increase in bio-ADM concentration with increasing prevalence of rales: 29.8 [18.8-51.1], 38.5 [27.5-67.1], and 51.1 [33.1-103.2] ng/L in patients with no rales, rales covering less than one-half, and greater than or equal to one-half of the pulmonary area, respectively (P < 0.001). Bio-ADM concentration demonstrated gradual elevation in patients with normal, moderately, and severely increased estimated right atrial pressure: 25.1 [17.6-42.4] ng/L, 36.1 [23.1-50.2], and 47.1 [30.7-86.7] ng/L, respectively (P < .05). Patients with bio-ADM concentration >35.5 ng/L were at more than twofold increased risk of dying (P < .001). Survival in those with high bio-ADM was significantly modified by neurohormonal blockade at admission (P < .05), especially if NT-proBNP levels were lower than the median (P = .002 for interaction).ConclusionBio-ADM reflects the presence and the degree of pulmonary, peripheral, and intravascular volume overload and is strongly related to 90-day mortality in acute dyspnea. Patients with high bio-ADM levels demonstrated survival benefit from neurohormonal blockade.