An Observational Study on Cosmetics Use-related Adverse Effects: Cosmetovigilance Need of the Day.

INTRODUCTION: The pursuit of aesthetic attractiveness and increased awareness have contributed significantly to the growth of the cosmetic industry. However, it is crucial to recognize that even the minimal use of cosmetics may have harmful consequences for both the overall well-being and the broader community, an issue that has yet to be adequately recognized or addressed. OBJECTIVE: This study is aimed at providing insights into the usage pattern of consumer behavior regarding skin care products and to assess the prevalence and determinants of cosmetic-related adverse events among the general populace. MATERIALS AND METHODS: A community-based cross-sectional study was carried out for four months in a satellite city of the National Capital Region (NCR) of India. The data from 435 respondents was collected using a self-administered questionnaire and analyzed using frequencies and percentages. RESULTS: Among 435 participants, 32.9% experienced one or more adverse effects owing to the use of skincare products; the prevalence was higher in females (36.3%). Hair loss, allergies, and dry skin were the most frequently reported adverse effects. The majority of the adverse reactions were reported with soap (21%), followed by shampoo (17%). The gender-wise difference between adverse effects of skin care products was found to be statistically significant. CONCLUSION: To improve the system's efficiency, a comprehensive review of the current regulatory protocols for cosmetics is crucial. Additionally, it is essential to widely disseminate information on Cosmetovigilance and promote the reporting of any adverse effects of cosmetics within the community; this is the demand of the present time.

Facile and Scalable Development of High-Performance Carbon-Free Tin-Based Anodes for Sodium-Ion Batteries.

Tin (Sn)-based anodes for sodium (Na)-ion batteries possess higher Na-storage capacity and better safety aspects compared to hard carbon -based anodes but suffer from poor cyclic stability due to volume expansion/contraction and concomitant loss in mechanical integrity during sodiation/desodiation. To address this, the usage of nanoscaled electrode-active particles and nanoscaled-carbon-based buffers has been explored, but with compromises with the tap density, accrued irreversible surface reactions, overall capacity (for "inactive" carbon), and adoption of non-scalable/complex preparation routes. Against this backdrop, anode-active "layered" bismuth (Bi) has been incorporated with Sn via a facile-cum-scalable mechanical-milling approach, leading to individual electrode-active particles being composed of well-dispersed Sn and Bi phases. The optimized carbon-free Sn-Bi compositions, benefiting from the combined effects of "buffering" action and faster Na transport of Bi, to go with the greater Na-storage capacity and lower operating potential of Sn, exhibit excellent cyclic stability (viz., ∼83-92% capacity retention after 200 cycles at 1C) and rate capability (viz., no capacity drop from C/5 to 2C, with only ∼25% drop at 5C), despite having fairly coarse particles (∼5-10 µm). As proven by operando synchrotron X-ray diffraction and stress measurements, the sequential sodiation/desodiation of the components and, concomitantly, stress build-ups at different potentials provide "buffering" action even for such "active-active" Sn-Bi compositions. Furthermore, the overall stress development upon sodiation of Bi has been found to be significantly lower than that of Sn (by a factor of ∼3.8), which renders Bi promising as a "buffer" material, in general. Dissemination of such complex interplay between electrode-active components during electrochemical cycling also paves the way for the development of high-performance, safe, and scalable "alloying-reaction"-based anode materials for Na-ion batteries and beyond, sans the need for ultrafine/nanoscaled electrode particles or "inactive" nanoscaled-carbon-based "buffer" materials.

Adverse Event Following Immunization (AEFI) in Children: An Analysis of Reporting in VigiAccess.

INTRODUCTION: It is an indubitable fact that vaccination has been instrumental in the eradication and prevention of the deadliest diseases worldwide. Continuous vaccine safety surveillance is helpful to counter the negative perception and thus allay the fear of Adverse Events Following Immunization (AEFI) in the general public. VigiAccess, the WHO global database of reported side effects of medicinal products, can be accessed by the public at large. The objective of this study is to assess the characteristics of AEFIs of the commonly used vaccines in children in VigiAccess. MATERIALS AND METHODS: VigiAccess was thoroughly explored for the categories, number, and types of AEFIs of commonly used vaccines among children that are reported in five continents between 2011 and 2021. RESULTS: After a comprehensive analysis in VigiAccess, 27 kinds of AEFIs were discovered. For the nine vaccines, a total of 1,412,339 AEFIs were found. The most prevalent AEFIs were general disorder and administration site condition (436,199 or 30%). The majority of AEFIs are found in America, with Europe, Oceania, Asia, and Africa following closely behind. Girls of age from 27 days to 23 months had the highest number of AEFIs. The highest number of AEFIs was recorded in the year 2018. CONCLUSION: America has the maximum, whilst Africa has the least AEFI. Few AEFIs were caused by the measles vaccination, while the majority were related to the general disorder and administration site condition. Data synchronization in VigiAccess needs to be enhanced to improve its dependability.

Crystal Structure of a Soluble APOBEC3G Variant Suggests ssDNA to Bind in a Channel that Extends between the Two Domains.

APOBEC3G (A3G) is a single-stranded DNA (ssDNA) cytosine deaminase that can restrict HIV-1 infection by mutating the viral genome. A3G consists of a non-catalytic N-terminal domain (NTD) and a catalytic C-terminal domain (CTD) connected by a short linker. While the CTD catalyzes cytosine deamination, the NTD is believed to provide additional affinity for ssDNA. Structures of both A3G domains have been solved individually; however, a full-length A3G structure has been challenging. Recently, crystal structures of full-length rhesus macaque A3G variants were solved which suggested dimerization mechanisms and RNA binding surfaces, whereas the dimerization appeared to compromise catalytic activity. We determined the crystal structure of a soluble variant of human A3G (sA3G) at 2.5 Å and from these data generated a model structure of wild-type A3G. This model demonstrated that the NTD was rotated 90° relative to the CTD along the major axis of the molecule, an orientation that forms a positively charged channel connected to the CTD catalytic site, consisting of NTD loop-1 and CTD loop-3. Structure-based mutations, in vitro deamination and DNA binding assays, and HIV-1 restriction assays identify R24, located in the NTD loop-1, as essential to a critical interaction with ssDNA. Furthermore, sA3G was shown to bind a deoxy-cytidine dinucleotide near the catalytic Zn2+, yet not in the catalytic position, where the interactions between deoxy-cytidines and CTD loop-1 and loop-7 residues were different from those formed with substrate. These new interactions suggest a mechanism explaining why A3G exhibits a 3' to 5' directional preference in processive deamination.

Unravelling the role of long non-coding RNA - LINC01087 in breast cancer.

Apoptosis is a 'programmed fate' of all cells participating in diverse physiological and pathological conditions. The role of critical regulators and their involvement in this complex multi-stage process of apoptosis weaved around non-coding RNAs (ncRNAs) is poorly deciphered in breast carcinoma (BC). Aberrant expression patterns of the ncRNAs and their interacting partners, either ncRNAs or coding RNAs or proteins at any point along these pathways, may lead to the malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Longest non-coding type of ncRNAs (lncRNAs) have been considered as critical factors for the development and progression of breast cancer. The aim of our study was to identify set of novel lncRNAs interacting with microRNAs (miRNAs) or proteins that were significantly dysregulated in breast cancer using RNA-Sequencing (RNA-Seq) technique in different samples acting as oncogenic drivers contributing to cancerous phenotype involved in post-transcriptional processing of RNAs. Four lncRNAs; LINC01087, lnc-CLSTN2-1:1, lnc-c7orf65-3:3 and LINC01559:2 were selected for further analysis. Gene expression analysis of over-expressed LINC01087 in vitro reduced both cell viability and apoptosis. We integrated miRNA and mRNA (hsa-miR-548 and AKT1) expression profiles with curated regulations with lncRNA (LINC01087) which has not been previously associated with any breast cancer type, using different computational tools. The network (lncRNA→ miRNA→ mRNA) is promising for the identification of carcinoma associated genes and apoptosis signaling path highlighting the potential roles of LINC01087, hsa-miR548n, AKT1 gene which may play crucial role in proliferation.

Phytoconstituents of an ethanolic pod extract of Prosopis cineraria triggers the inhibition of HMG-CoA reductase and the regression of atherosclerotic plaque in hypercholesterolemic rabbits.

BACKGROUND: The HMG-CoA reductase is key enzyme of cholesterol biosynthesis which potentially contributes in management of hypercholesterolemia. The present study was designed to assess the inhibitory effect of phytoconstituents of an ethanolic extract of Prosopis cineraria pods on HMG - CoA reductase and regression potential of atherosclerotic plaque. METHODS: Healthy, adult male, albino rabbits in which hypercholesterolemia was induced by supplying the high fat diet and a supplement of cholesterol powder with coconut oil (500 mg/5 ml/Day/kg body weight) for 15 days, were used as a disease model. Phytochemical analysis of an ethanolic extract Prosopis cineraria pods was conducted using LCMS, GCMS and FTIR analysis. Further, in-vitro, in-vivo and in-silico assessments were performed. RESULTS: The in-vitro assessment of HMG -CoA reductase activity indicated a 67.1 and 97.3% inhibition by the extract and a standard drug (Pravastatin), respectively. Additionally, an in-silico evaluation was made using appropriate docking software and results also indicated as significant interactions of the identified compounds with the target enzyme. Treatment of rabbits with the ethanolic extract of P. cineraria pod resulted in significant (P ≤ 0.001) reductions in total cholesterol, LDL cholesterol, VLDL cholesterol, and triglyceride. Accordingly, reductions were occurred in atherosclerotic plaque, intima and media of aortal wall along with lumen volume of the aorta significantly increased (P ≤ 0.001). CONCLUSION: It can be illustrating that the ethanolic extract of Prosopis cineraria pod contains potent bioactive phytocompounds might be inhibit HMG - CoA reductase and have regression potential of atherosclerotic plaque.

Mechanism for APOBEC3G catalytic exclusion of RNA and non-substrate DNA.

The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of substrate ssDNA from non-substrate. Using 2'-deoxy-2'-fluorine substituted cytidines, we show that a 2'-endo sugar conformation of the target deoxycytidine is favored for substrate binding and deamination. Trajectories of the MD simulation indicate that a ribose 2'-hydroxyl group destabilizes the π-π stacking of the target cytosine and H257, resulting in dislocation of the target cytosine base from the catalytic position. Interestingly, APOBEC3A, which can deaminate ribocytidines, retains the ribocytidine in the catalytic position throughout the MD simulation. Our results indicate that A3Gctd catalytic selectivity against RNA is dictated by both the sugar conformation and 2'-hydroxyl group.

Unraveling long non-coding RNAs through analysis of high-throughput RNA-sequencing data.

Extensive genome-wide transcriptome study mediated by high throughput sequencing technique has revolutionized the study of genetics and epigenetic at unprecedented resolution. The research has revealed that besides protein-coding RNAs, large proportions of mammalian transcriptome includes a heap of regulatory non protein-coding RNAs, the number encoded within human genome is enigmatic. Many taboos developed in the past categorized these non-coding RNAs as ''dark matter" and "junks". Breaking the myth, RNA-seq-- a recently developed experimental technique is widely being used for studying non-coding RNAs which has acquired the limelight due to their physiological and pathological significance. The longest member of the ncRNA family-- long non-coding RNAs, acts as stable and functional part of a genome, guiding towards the important clues about the varied biological events like cellular-, structural- processes governing the complexity of an organism. Here, we review the most recent and influential computational approach developed to identify and quantify the long non-coding RNAs serving as an assistant for the users to choose appropriate tools for their specific research.

Integrated analysis of dysregulated lncRNA expression in breast cancer cell identified by RNA-seq study.

Among all the sequencing techniques, RNA sequencing (RNA-seq) has galloped with pace adopting the profiling of transcriptomic data in almost every biological analytics area like gene regulation study, development biology and clinical research. Recently the discovery of differentially expressed genes across different conditions has outshone the barrier of genetic & epigenetic regulations. The present work identified and analyzed differentially expressed novel long non-coding RNAs (lncRNAs) for breast cancer. A complex computational pipeline was adopted for the study which includes analysis of 18498 differentially expressed genes with 4114 up-regulated and 3475 down-regulated transcripts. The overexpression of lnc-MTAP (CDKN2B-AS1), lnc-PCP4 (DSCAM-S1), and lnc-FAM (H19) in breast cells suggests that these lncRNAs may have significant role to play in breast cancer. These results validated the relevance of the dysregulation pattern in cancer cells due to the presence of lncRNAs. The study further opens a new scope for experimental analysis to confirm the aberrant expression pattern of these lncRNAs which may act as potential bio-markers for the diagnosis and early detection of breast cancer.

Biophysical characterisation of calumenin as a charged F508del-CFTR folding modulator.

The cystic fibrosis transmembrane regulator (CFTR) is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflammation of human airways observed in cystic fibrosis (CF) patients. The process by which CFTR folds and matures under the influence of various chaperones in the secretory pathway remains incompletely understood. Recently, calumenin, a secretory protein, belonging to the CREC family of low affinity calcium binding proteins has been identified as a putative CFTR chaperone whose biophysical properties and functions remain uncharacterized. We compared hydropathy, instability, charge, unfoldability, disorder and aggregation propensity of calumenin and other CREC family members with CFTR associated chaperones and calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically disordered proteins (IDPs). We observed that calumenin, along with other CREC proteins, was significantly more charged and less folded compared to CFTR associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were found to be less hydrophobic and aggregation prone. Phylogenetic analysis revealed a close link between calumenin and other CREC proteins indicating how evolution might have shaped their similar biophysical properties. Experimentally, calumenin was observed to significantly reduce F508del-CFTR aggregation in a manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy based imaging analysis also revealed altered trafficking of calumenin in bronchial cells expressing F508del-CFTR, indicating its direct role in the pathophysiology of CF. In conclusion, calumenin is characterized as a charged protein exhibiting close similarity with IDPs and is hypothesized to regulate F508del-CFTR folding by electrostatic effects. This work provides useful insights for designing optimized synthetic structural correctors of CFTR mutant proteins in the future.

Trafficking of bdelloid rotifer late embryogenesis abundant proteins.

The bdelloid rotifer Adineta ricciae is an asexual microinvertebrate that can survive desiccation by entering an ametabolic state known as anhydrobiosis. Two late embryogenesis abundant (LEA) proteins, ArLEA1A and ArLEA1B, have been hypothesized to contribute to desiccation tolerance in these organisms, since in vitro assays suggest that ArLEA1A and ArLEA1B stabilize desiccation-sensitive proteins and membranes, respectively. To examine their functions in vivo, it is important to analyse the cellular distribution of the bdelloid LEA proteins. Bioinformatics predicted their translocation into the endoplasmic reticulum (ER) via an N-terminal ER translocation signal and persistence in the same compartment via a variant C-terminal retention signal sequence ATEL. We assessed the localization of LEA proteins in bdelloids and in a mammalian cell model. The function of the N-terminal sequence of ArLEA1A and ArLEA1B in mediating ER translocation was verified, but our data showed that, unlike classical ER-retention signals, ATEL allows progression from the ER to the Golgi and limited secretion of the proteins into the extracellular medium. These results suggest that the N-terminal ER translocation signal and C-terminal ATEL sequence act together to regulate the distribution of rotifer LEA proteins within intracellular vesicular compartments, as well as the extracellular space. We speculate that this mechanism allows a small number of LEA proteins to offer protection to a large number of desiccation-sensitive molecules and structures both inside and outside cells in the bdelloid rotifer.

Intrinsically disordered proteins as molecular shields.

The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins. We show here that this activity, termed molecular shield function, is distinct from that of a classical molecular chaperone, such as HSP70 - while HSP70 reduces aggregation of citrate synthase (CS) on heating, two LEA proteins, a nematode group 3 protein, AavLEA1, and a plant group 1 protein, Em, do not; conversely, the LEA proteins reduce CS aggregation on desiccation, while HSP70 lacks this ability. There are also differences in interaction with client proteins - HSP70 can be co-immunoprecipitated with a polyglutamine-containing client, consistent with tight complex formation, whereas the LEA proteins can not, although a loose interaction is observed by Förster resonance energy transfer. In a further exploration of molecular shield function, we demonstrate that synthetic polysaccharides, like LEA proteins, are able to reduce desiccation-induced aggregation of a water-soluble proteome, consistent with a steric interference model of anti-aggregation activity. If molecular shields operate by reducing intermolecular cohesion rates, they should not protect against intramolecular protein damage. This was tested using the monomeric red fluorescent protein, mCherry, which does not undergo aggregation on drying, but the absorbance and emission spectra of its intrinsic fluorophore are dramatically reduced, indicative of intramolecular conformational changes. As expected, these changes are not prevented by AavLEA1, except for a slight protection at high molar ratios, and an AavLEA1-mCherry fusion protein is damaged to the same extent as mCherry alone. A recent hypothesis proposed that proteomes from desiccation-tolerant species contain a higher degree of disorder than intolerant examples, and that this might provide greater intrinsic stability, but a bioinformatics survey does not support this, since there are no significant differences in the degree of disorder between desiccation tolerant and intolerant species. It seems clear therefore that molecular shield function is largely an intermolecular activity implemented by specialist IDPs, distinct from molecular chaperones, but with a role in proteostasis.

Messenger RNA and microRNA profiling during early mouse EB formation.

Embryonic stem (ES) cells can be induced to differentiate into embryoid bodies (EBs) in a synchronised manner when plated at a fixed density in hanging drops. This differentiation procedure mimics post-implantation development in mouse embryos and also serves as the starting point of protocols used in differentiation of stem cells into various lineages. Currently, little is known about the potential influence of microRNAs (miRNAs) on mRNA expression patterns during EB formation. We have measured mRNA and miRNA expression in developing EBs plated in hanging drops until day 3, when discrete structural changes occur involving their differentiation into three germ layers. We observe significant alterations in mRNA and miRNA expression profiles during this early developmental time frame, in particular of genes involved in germ layer formation, stem cell pluripotency and nervous system development. Computational target prediction using Pictar, TargetScan and miRBase Targets reveals an enrichment of binding sites corresponding to differentially and highly expressed miRNAs in stem cell pluripotency genes and a neuroectodermal marker, Nes. We also find that members of let-7 family are significantly down-regulated at day 3 and the corresponding up-regulated genes are enriched in let-7 seed sequences. These results depict how miRNA expression changes may affect the expression of mRNAs involved in EB formation on a genome-wide scale. Understanding the regulatory effects of miRNAs during EB formation may enable more efficient derivation of different cell types in culture.

Anticonvulsant activity of bacopa monniera in rodents / Anticonvulsivante atividade de bacopa monniera em roedores

Bacopa monnieri (L), belonging to the Scrophulariaceae family and commonly known as Brahmi, is well known in India for its CNS activity but its neuropharmacological effect has not yet been explored. In the present study, the antiepileptic effects of the plant were investigated. The ethanolic extract of Bacopa monniera was tested for anticonvulsant activity in albino rats, using different convulsive models. The ethanolic extract of leaves produced significant anticonvulsant activity for all the different models studied. The present study shows a probable mechanism of action similar to that of benzodiazepines (GABA agonist). Thus, these results emphasize the need to diversify by using alternative therapeutic approaches pertaining to herbal medicine, where a single easily available plant may provide solutions to several therapeutic challenges, as observed in the anticonvulsant action of ethanolic extract of B. monniera.

Bacopa monniera, da família Scrophulariaceae, e comumente denominada Brahmi, é bem conhecida na Índia por sua atividade no Sistema Nervoso Central, mas seu efeito neurofarmacológico não foi, ainda, explorado. No presente estudo, investigaram-se os efeitos antiepilépticos da planta. O extrato etanólico da Bacopa monniera foi testado quanto à atividade anticonvulsivante em ratos albinos, utilizando-se diferentes modelos de convulsão. O extrato etanólico das folhas produziu atividade anticonvulsivante significativa para todos os diferentes modelos estudados. O presente estudo mostra provável mecanismo de ação semelhante ao dos benzodiazepínicos (agonista do GABA). Assim sendo, esses resultados enfatizam a necessidade de diversificar, utilizando-se abordagens terapêuticas alternativas da medicina natural, em que uma planta facilmente disponível pode fornecer soluções para vários desafios terapêuticos, como o observado na ação anticonvulsivante do extrato etanólico de Bacopa monniera.