SOLID LIPID NANOPARTICLE: FABRICATED THROUGH NANOPRECIPITATION AND THEIR PHYSICOCHEMICAL CHARACTERIZATION

Objective: Aim of the present study was to formulate solid lipid nanoparticles (SLNs) and to determine their physicochemical parameters when stored at cold temperature in aqueous solution (D-SLNs) prior to biological application.Methods: SLNs were formulated though nanoprecipitation technique which comprised of stearic acid (lipid), poloxamer 188 and lecithin (surfactant). Physicochemical parameters were estimated though particle size analysis, polydispersity index, surface morphology analysis (Scanning electron microscopy and Transmission electron microscopy) and cytotoxicity studies followed by live-dead staining through acridine orange and ethidium bromide.Results: SLNs with spherical morphology were successfully fabricated as revealed though SEM and TEM investigations. Fabricated SLNs had the mean particle size ranging from 188 nm (SLNs) to 327 nm (D-SLNs). Zeta potential was found to be±14mV to±6mV and polydispersity index was 0.297±0.18 for SLNs without incubation and 0.538±0.07 for SLNs after incubation. No cytotoxicity was observed for SLNs.Conclusion: SEM and TEM investigations showed morphological variation in SLNs and D-SLNs. Dissimilarity in mean particle size, zeta potential and polydispersity index indicates the increase in size and aggregation of nanoparticles. No cytotoxic effects of SLNs were observed in normal cells, suggesting storage of nanoformulation in the aqueous state has no effect in context to cytotoxicity. Hence we conclude that prolonged storage of formulation at cold temperature causes the deterioration of polymeric formulation

Rehabilitation Exercise Repetition Segmentation and Counting using Skeletal Body Joints

Physical exercise is an essential component of rehabilitation programs that improve quality of life and reduce mortality and re-hospitalization rates. In AI-driven virtual rehabilitation programs, patients complete their exercises independently at home, while AI algorithms analyze the exercise data to provide feedback to patients and report their progress to clinicians. To analyze exercise data, the first step is to segment it into consecutive repetitions. There has been a significant amount of research performed on segmenting and counting the repetitive activities of healthy individuals using raw video data, which raises concerns regarding privacy and is computationally intensive. Previous research on patients' rehabilitation exercise segmentation relied on data collected by multiple wearable sensors, which are difficult to use at home by rehabilitation patients. Compared to healthy individuals, segmenting and counting exercise repetitions in patients is more challenging because of the irregular repetition duration and the variation between repetitions. This paper presents a novel approach for segmenting and counting the repetitions of rehabilitation exercises performed by patients, based on their skeletal body joints. Skeletal body joints can be acquired through depth cameras or computer vision techniques applied to RGB videos of patients. Various sequential neural networks are designed to analyze the sequences of skeletal body joints and perform repetition segmentation and counting. Extensive experiments on three publicly available rehabilitation exercise datasets, KIMORE, UI-PRMD, and IntelliRehabDS, demonstrate the superiority of the proposed method compared to previous methods. The proposed method enables accurate exercise analysis while preserving privacy, facilitating the effective delivery of virtual rehabilitation programs.Comment: 8 pages, 1 figure, 2 table

Dementia with Lewy Bodies: Genomics, Transcriptomics, and Its Future with Data Science

Dementia with Lewy bodies (DLB) is a significant public health issue. It is the second most common neurodegenerative dementia and presents with severe neuropsychiatric symptoms. Genomic and transcriptomic analyses have provided some insight into disease pathology. Variants within SNCA, GBA, APOE, SNCB, and MAPT have been shown to be associated with DLB in repeated genomic studies. Transcriptomic analysis, conducted predominantly on candidate genes, has identified signatures of synuclein aggregation, protein degradation, amyloid deposition, neuroinflammation, mitochondrial dysfunction, and the upregulation of heat-shock proteins in DLB. Yet, the understanding of DLB molecular pathology is incomplete. This precipitates the current clinical position whereby there are no available disease-modifying treatments or blood-based diagnostic biomarkers. Data science methods have the potential to improve disease understanding, optimising therapeutic intervention and drug development, to reduce disease burden. Genomic prediction will facilitate the early identification of cases and the timely application of future disease-modifying treatments. Transcript-level analyses across the entire transcriptome and machine learning analysis of multi-omic data will uncover novel signatures that may provide clues to DLB pathology and improve drug development. This review will discuss the current genomic and transcriptomic understanding of DLB, highlight gaps in the literature, and describe data science methods that may advance the field

Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress

The objective of this investigation was to evaluate the influence of micro- and nanoplastic particles composed of polyethylene terephthalate (PET), a significant contributor to plastic pollution, on human brain vascular pericytes. Specifically, we delved into their impact on mitochondrial functionality, oxidative stress, and the expression of genes associated with oxidative stress and ferroptosis. Our findings demonstrate that the exposure of a monoculture of human brain vascular pericytes to PET particles in vitro at a concentration of 50 ppm for a duration of 6 days did not elicit oxidative stress. Notably, we observed an augmentation in various aspects of mitochondrial respiration, including extracellular acidification, proton pump leakage, maximal respiration, spare respiratory capacity, and ATP production in pericytes subjected to PET particles. Furthermore, there were no statistically significant alterations in mitochondrial DNA copy number, or the expression of genes linked to oxidative stress and ferroptosis. These outcomes suggest that, at a concentration of 50 parts per million (ppm) and for 6 days exposure, PET particles do not induce oxidative stress in human brain vascular pericytes. Instead, they seem to incite a potential mitochondrial hormesis, also named mitohormesis, response, which seemingly enhances mitochondrial function. Further investigations are warranted to explore the stages of mitohormesis and the potential consequences of plastics on the integrity of the blood-brain barrier and intercellular interactions. This research contributes to our comprehension of the potential repercussions of nanoplastic pollution on human health and underscores the imperative need for ongoing examinations into the exposure to plastic particles

In Vivo Delivery of Tinospora cordifolia Root Extract Preventing Radiation-Induced Dystrophies in Mice Ovaries

Unconscious and unplanned radiation exposures are a severe threat to gonads particularly ovaries. The present study aims at finding radioprotective effect of Tinospora cordifolia (Willd.) Miers root extract (TCRE) in ovaries. Swiss albino mice were divided into four groups: Group 1 served as “normal” and is administered double distilled water and Group 2 is given TCRE with optimum dosage selected as 75 mg/mice. Group 3 serving the purpose of “irradiated control” were exposed to 2.5 Gy gamma radiation. Group 4 (experimental) were administered optimum dosage of TCRE with prior exposure to 2.5 Gy gamma radiation. Follicle cell counts were scored at autopsy intervals of 24 hrs, 3 days, 7 days, 15 days, and 30 days after gamma irradiation. To understand the mechanism of radioprotection, lipid peroxidation (LPO) and glutathione (GSH) levels were also measured in all groups. TCRE supplementation rendered significant protection to ovaries by restoring follicle counts; it also reduced LPO levels and increased GSH levels in ovaries. It implies that TCRE administration protects ovaries against radiation exposure

iPS Cells—The Triumphs and Tribulations

The year 2006 will be remembered monumentally in science, particularly in the stem cell biology field, for the first instance of generation of induced pluripotent stem cells (iPSCs) from mouse embryonic/adult fibroblasts being reported by Takahashi and Yamanaka. A year later, human iPSCs (hiPSCs) were generated from adult human skin fibroblasts by using quartet of genes, Oct4, Sox2, Klf4, and c-Myc. This revolutionary technology won Yamanaka Nobel Prize in Physiology and Medicine in 2012. Like human embryonic stem cells (hESCs), iPSCs are pluripotent and have the capability for self-renewal. Moreover, complications of immune rejection for therapeutic applications would be greatly eliminated by generating iPSCs from individual patients. This has enabled their use for drug screening/discovery and disease modelling in vitro; and for immunotherapy and regenerative cellular therapies in vivo, paving paths for new therapeutics. Although this breakthrough technology has a huge potential, generation of these unusual cells is still slow, ineffectual, fraught with pitfalls, and unsafe for human use. In this review, I describe how iPSCs are being triumphantly used to lay foundation for a fully functional discipline of regenerative dentistry and medicine, alongside discussing the challenges of translating therapies into clinics. I also discuss their future implications in regenerative dentistry field

Strike-Slip Faulting in the Eastern Himalaya and Indo-Burman Plate Boundary Systems

EGU General Assembly in Vienna, Austria, 7–12 April 2019Northeast India is sandwiched between the seismically active plate boundaries of the Eastern Himalaya to the north and the Indo-Burman subduction zone to the east. This plate boundary system is different from the central Nepal Himalaya, due to oblique convergence across two orthogonal plate boundaries, resulting in a zone of distributed deformation both within and away from the plate boundary. Previous studies of spatial distribution and source mechanism of earthquakes have shown that the N20E convergence between India and Tibet is partitioned into N-S underthrusting and E-W subduction of the Indian plate beneath the Himalaya and Burma micro-plate, respectively. However, south-west of the plate boundaries, the middle-to-lower crust deforms by strike-slip faulting in the Kopilli Fault Zone (KFZ); upper-to-mid crustal strike-slip faulting along the western Brahmaputra Valley; and lower crustal strike-slip faulting beneath the Bengal Basin. Strike-slip faulting in the KFZ also extends northwards beneath the Eastern Himalaya and southeastward beneath the Naga fold-thrust belt. In order to understand the role of these strike-slip faults in accommodating the GPS derived convergence across northeast India, we study the source mechanism of recent earthquakes using teleseismic (for earthquakes with Mw>5) and local (4.0<Mw<5) waveform inversion. Our results of earthquake source parameters, directivity effects, and source mechanisms reveal dextral strike-slip faults in the KFZ and the western Brahmaputra Valley. We conjecture that the strike-slip faults in the Bengal Basin are reactivated passive continental margin rift faults with left-lateral motion. We will combine our results with previous studies of well-constrained source mechanisms and GPS velocity field to unravel the kinematics of active deformation across northeast India

Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review