Efficacy of encapsulated biogenic silver nanoparticles and its disease resistance against Vibrio harveyi through oral administration in Macrobrachium rosenbergii.

Biological synthesis of silver nanoparticles (AgNPs) by Cheatomorpha antennia and its in vitro and in vivo antibacterial activity against Vibrio harveyi in Macrobrachium rosenbergii was demonstrated in the study. In vitro growth curve analysis, cell viability and bacterial inhibitory assays were performed to test the efficacy of synthesised AgNPs against bacteria. Sodium caseinate was used as an encapsulating agent to deliver the antibacterial drugs and the commercial process of microencapsulation comprises the antibacterial bioelements for oral administration to improve the disease resistance of AgNPs against V. harveyi due to the eco-friendly for non-toxic behaviour of nanoparticle and their treatment. Characterisation of antibacterial silver was performed by UV spectroscopy, X-ray diffraction, Fourier Transform Infrared spectroscopy and Scanning Electron Microscopy. The peak at 420 nm showed the presence of nanoparticles in the solution and the crystal nature of the particle was identified by the XRD. FTIR characterised the functional harveyi biomolecules and further SEM confirmed the size of the nanoparticles around 24 ± 2.4 nm. Experimental pathogenicity of V. harveyi showed 100% mortality at the 120th hour. Treatment of encapsulated AgNPs was administered orally for the relative percentage of survival which acquired almost 90% of survival till 30 days of exposure. In conclusion, the microencapsulation of AgNPs in the biopolymer matrices promotes the health, growth responses, immunity and disease resistance of encapsulated AgNPs with an improved relative percentage of survival.

Alpha-Synuclein Aggregation in Parkinson's Disease.

Parkinson's disease (PD), a neurodegenerative disorder characterized by distinct aging-independent loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region urging toward neuronal loss. Over the decade, various key findings from clinical perspective to molecular pathogenesis have aided in understanding the genetics with assorted genes related with PD. Subsequently, several pathways have been incriminated in the pathogenesis of PD, involving mitochondrial dysfunction, protein aggregation, and misfolding. On the other hand, the sporadic form of PD cases is found with no genetic linkage, which still remain an unanswered question? The exertion in ascertaining vulnerability factors in PD considering the genetic factors are to be further dissevered in the forthcoming decades with advancement in research studies. One of the major proponents behind the prognosis of PD is the pathogenic transmutation of aberrant alpha-synuclein protein into amyloid fibrillar structures, which actuates neurodegeneration. Alpha-synuclein, transcribed by SNCA gene is a neuroprotein found predominantly in brain. It is implicated in the modulation of synaptic vesicle transport and eventual release of neurotransmitters. Due to genetic mutations and other elusive factors, the alpha-synuclein misfolds into its amyloid form. Therefore, this review aims in briefing the molecular understanding of the alpha-synuclein associated with PD.

Seminal exosomes - An important biological marker for various disorders and syndrome in human reproduction.

BACKGROUND: Exosomes are nano-sized membrane vesicles, secreted by different types of cells into the body's biological fluids. They are found in abundance in semen as compared to other fluids. Exosomes contain a cargo of lipid molecules, proteins, phospholipids, cholesterol, mRNAs, and miRNAs. Each molecule of seminal exosomes (SE) has a potential role in male reproduction for childbirth. Many potential candidates are available within the seminal exosomes that can be used as diagnostic markers for various diseases or syndromes associated with male reproduction. Also these seminal exospmes play a major role in female reproductive tract for effective fertilization. AIM: The aim of this review is to focus on the advancement of human seminal exosomal research and its various properties. METHODS: We used many databases like Scopus, Google scholar, NCBI-NLM and other sources to filter the articles of interest published in exosomes. We used phrases like "Exosomes in human semen", "Composition of exosomes in human semen" and other relevant words to filter the best articles. RESULTS: Seminal exosomes play a major role in sperm functions like cell-to-cell communication, motility of the sperm cells, maintaining survival capacity for the sperm in the female reproductive tract and spermatogenesis. Also, seminal exosomes are used as a carrier for many regulatory elements using small RNA molecules. miRNAs of the seminal exosomes can be used as a diagnostic marker for prostate cancer instead of prostate specific antigen (PSA). Epididymosomes can be used as a biomarker for reproductive diseases and male infertility. CONCLUSION: Seminal exosomes could be used as biological markers for various reproductive disorders, male infertility diagnosis, and it can be used in anti-retroviral research for the identification of novel therapeutics for HIV-1 infection and transmission.

A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin.

The crystallins are a family of monomeric proteins present in the mammalian lens and mutations in these proteins cause various forms of cataracts. The aim of our current study is to emphasize the structural characterization of aggregation propensity of mutation R58H on γD crystallin using molecular dynamics (MD) approach. MD result revealed that difference in the sequence level display a wide variation in the backbone atomic position, and thus exhibits rigid conformational dynamics. Changes in the flexibility of residues favoured to increase the number of intra-molecular hydrogen bonds in mutant R58H. Moreover, notable changes in the hydrogen bonding interaction resulted to cause the misfolding of mutant R58H by introducing α-helix. Principal component analysis (PCA) result suggested that mutant R58H showed unusual conformational dynamics along the two principal components when compared to the wild-type (WT)-γD crystallin. In a nutshell, the increased surface hydrophobicity could be the cause of self-aggregation of mutant R58H leading to aculeiform cataract.

Assessment of Hematological Parameters in Pulmonary Tuberculosis Patients.

The aim of the study was the assessment of hematological parameters in pulmonary tuberculosis patients. Forty patients diagnosed with tuberculosis were recruited from the Institute of Thoracic Medicine on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters and were compared with age and sex matched healthy volunteers (n = 40). Hematological parameters and CRP in tuberculosis patients were determined. The mean values for serum hemoglobin level, RBC count and platelet count in PTB was found to be less (p < 0.001). Erythrocyte sedimentation rate (ESR), plasma C-reactive protein, WBC count in PTB subjects was increased (p < 0.001 for ESR & CRP, p < 0.05 for WBCs) and all were statistically significant. This study demonstrated that serum hemoglobin level, RBC count and platelet count was decreased in tuberculosis patients whereas ESR, CRP and WBC count was increased when compared with healthy controls.

Serum PCT and its Relation to Body Weight Gain in Pulmonary Tuberculosis.

The present study was aimed at assessing alterations in serum PCT in terms of its relation to body weight gain in pulmonary tuberculosis (PTB) patients undergoing treatment. Among patients (25-75 years) diagnosed with pulmonary tuberculosis, those that were new smear positive, showed sputum conversion at the end of 2 months and were declared clinically cured at the end of 6 months, were included in the study (n = 40). Serum procalcitonin was determined by BRAHMS PCT-Q kit. Patients were divided into two study groups-Group 1 (n = 21; serum PCT > 2 ng/ml at diagnosis), Group 2 (n = 19; serum PCT > 10 ng/ml at diagnosis). Body weights of all patients were obtained at three different time points, PTB-0 (at diagnosis), PTB-2 (after 2 months of intensive treatment) and PTB-6 (after 6 months of treatment). In both groups, mean body weights at PTB-2 and PTB-6 were significantly higher than those at PTB-0 and at PTB-6 were significantly higher than those at PTB-2. However, percentage body weight gain following 2 months of intensive treatment was higher in group 1 (4.05 % gain, p < 0.01) than in group 2 (2.75 % body weight gain, p < 0.05). Thus, the percentage gain in group 1 was tending more towards the desirable minimum gain of 5 % during intensive phase. Increase in serum PCT levels in pulmonary tuberculosis is inversely associated with body weight gain during treatment. Thus, PCT could play a role in regulation of body weight gain in anorectic conditions like tuberculosis.

Assessment of serum calcium and phosphorus in pulmonary tuberculosis patients before, during and after chemotherapy.

Our study was aimed to assess the levels of serum calcium and phosphorus in pulmonary tuberculosis patients. Blood samples were collected from 40 patients with pulmonary tuberculosis before treatment (PTB-0), at the end of 2 months of intensive phase of treatment (PTB-2) and after 6 months of treatment (PTB-6). Age and weight matched normal healthy volunteers (n = 37) served as normal controls. Serum was analyzed for calcium and phosphorus. Serum calcium significantly decreased to hypocalcemic levels and serum phosphorus significantly decreased but was within normophosphatemic limits in pulmonary tuberculosis. Chemotherapy for tuberculosis managed to raise serum levels of both the ions, with hypocalcemia still persisting in majority of patients during treatment but getting resolved in a significant percentage of patients at the end of 6 months of treatment. Results indicate the need for calcium and phosphorus supplements in tuberculosis patients during chemotherapy. This study also warrants the need for regular monitoring of serum calcium and phosphorus in patients undergoing anti-tuberculosis treatment.

Molecular dynamics simulations and principal component analysis on human laforin mutation W32G and W32G/K87A.

Mutations in human laforin lead to an autosomal neurodegenerative disorder Lafora disease. In N-terminal carbohydrate binding domain of laforin, two mutations W32G and K87A are reported as highly disease causing laforin mutants. Experimental studies reported that mutations are responsible for the abolishment of glycogen binding which is a critical function of laforin. Our current computational study focused on the role of conformational changes in human laforin structure due to existing single mutation W32G and prepared double mutation W32G/K87A related to loss of glycogen binding. We performed 10 ns molecular dynamics (MD) simulation studies in the Gromacs package for both mutations and analyzed the trajectories. From the results, the global properties like root mean square deviation, root mean square fluctuation, radius of gyration, solvent accessible surface area and hydrogen bonds showed structural changes in atomic level observed in W32G and W32G/K87A laforin mutants. The conformational change induced by mutants influenced the loss of the overall stability of the native laforin. Moreover, the change in overall motion of protein was analyzed by principal component analysis and results showed protein clusters expanded more than native and also change in direction in case of double mutant in conformational space. Overall, our report provides theoretical information on loss of structure-function relationship due to flexible nature of laforin mutants. In conclusion, comparative MD simulation studies support the experimental data on W32G and W32G/K87A related to the lafora disease mechanism on glycogen binding.

Exploring the structural insights on human laforin mutation K87A in Lafora disease--a molecular dynamics study.

Lafora disease (LD) is an autosomal recessive, progressive form of myoclonus epilepsy which affects worldwide. LD occurs mainly in countries like southern Europe, northern Africa, South India, and in the Middle East. LD occurs with its onset mainly in teenagers and leads to decline and death within 2 to 10 years. The genes EPM2A and EPM2B are commonly involved in 90 % of LD cases. EPM2A codes for protein laforin which contains an amino terminal carbohydrate binding module (CBM) belonging to the CBM20 family and a carboxy terminal dual specificity phosphatase domain. Mutations in laforin are found to abolish glycogen binding and have been reported in wet lab methods. In order to investigate on structural insights on laforin mutation K81A, we performed molecular dynamics (MD) simulation studies for native and mutant protein. MD simulation results showed loss of stability due to mutation K87A which confirmed the structural reason for conformational changes observed in laforin. The conformational change of mutant laforin was confirmed by analysis using root mean square deviation, root mean square fluctuation, solvent accessibility surface area, radius of gyration, hydrogen bond, and principle component analysis. Our results identified that the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional CBM domain, have more impact in abolishing glycogen binding that favors LD.

Structural insights on Mycobacterium tuberculosis thiazole synthase--a molecular dynamics/docking approach.

Tuberculosis (TB), an epidemic disease, affects the world with death rate of two million people every year. The bacterium Mycobacterium tuberculosis was found to be a more potent and disease-prolonged bacterium among the world due to multi-drug resistance. Emergence of new drug targets is needed to overcome the bacterial resistance that leads to control epidemic tuberculosis. The pathway thiamine biosynthesis was targeting M. tuberculosis due to its role in intracellular growth of the bacterium. The screening of enzymes involved in thiamin biosynthesis showed novel target thiazole synthase (ThiG) involved in catalysis of rearrangement of 1-deoxy-D-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. We carried out homology modeling for ThiG to understand the structure-function relationship, and the model was refined with MD simulations. The results showed that the model predicted with (α + ß)8-fold of synthase family proteins. Molecular docking of ThiG model with substrate DXP showed binding mode and key residues ARG46, ASN69, THR41, and LYS96 involved in the catalysis. First-line anti-tuberculosis drugs were docked with ThiG to identify the inhibition. The report showed the anti-tuberculosis drugs interact well with ThiG which may lead to block thiamin biosynthesis pathway.