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.

Integrating Nanotechnological Advancements of Disease-Modifying Anti-Rheumatic Drugs into Rheumatoid Arthritis Management.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

An insight into the structure-activity relationship studies of anticancer medicinal attributes of 7-azaindole derivatives: a review.

In the current portfolio, there is a lot of interest in the 7-azaindole building block for drug discovery. The creation of synthetic, sophisticated methods for the modification of 7-azaindoles is a promising area of research. This review covers the structure-activity relationship of 7-azaindole analogs, which have been shown to be effective anticancer agents in the literature of the past two decades. Positions 1, 3 and 5 of the 7-azaindole ring are the most active sites. Disubstitution is used for the synthesis of a new analog of the 7-azaindole moiety. All positions are used to create novel molecules that are effective anticancer agents. The alkyl, aryl carboxamide group and heterocyclic ring are the most successful types of substitution.

Understanding the Therapeutic Approaches for Neuroprotection.

The term "neurodegenerative disorders" refers to a group of illnesses in which deterioration of nerve structure and function is a prominent feature. Cognitive capacities such as memory and decision-making deteriorate as a result of neuronal damage. The primary difficulty that remains is safeguarding neurons since they do not proliferate or regenerate spontaneously and are therefore not substituted by the body after they have been damaged. Millions of individuals throughout the world suffer from neurodegenerative diseases. Various pathways lead to neurodegeneration, including endoplasmic reticulum stress, calcium ion overload, mitochondrial dysfunction, reactive oxygen species generation, and apoptosis. Although different treatments and therapies are available for neuroprotection after a brain injury or damage, the obstacles are inextricably connected. Several studies have revealed the pathogenic effects of hypothermia, different breathed gases, stem cell treatments, mitochondrial transplantation, multi-pharmacological therapy, and other therapies that have improved neurological recovery and survival outcomes after brain damage. The present review highlights the use of therapeutic approaches that can be targeted to develop and understand significant therapies for treating neurodegenerative diseases.

A new class of teraryl-based AIEgen for highly selective imaging of intracellular lipid droplets and its detection in advanced-stage human cervical cancer tissues.

Lipid droplets (LDs) have drawn much attention in recent years. They serve as the energy reservoir of cells and also play an important role in numerous physiological processes. Furthermore, LDs are found to be associated with several pathological conditions, including cancer and diabetes mellitus. Herein, we report a new class of teraryl-based donor-acceptor-appended aggregation-induced emission luminogen (AIEgen), 6a, for selective staining of intracellular LDs in in vitro live 3T3-L1 preadipocytes and the HeLa cancer cell line. In addition, AIEgen 6a was found to be capable of staining and quantifying the LD accumulation in the tissue sections of advanced-stage human cervical cancer patients. Unlike commercial LD staining dyes Nile Red, BODIPY and LipidTOX, AIEgen 6a showed a high Stokes shift (195 nm), a good fluorescence lifetime decay of 12.7 ns, and LD staining persisting for nearly two weeks.

Exploring the molecular pathways and therapeutic implications of angiogenesis in neuropathic pain.

Recently, much attention has been paid to chronic neuro-inflammatory condition underlying neuropathic pain. It is generally linked with thermal hyperalgesia and tactile allodynia. It results due to injury or infection in the nervous system. The neuropathic pain spectrum covers a variety of pathophysiological states, mostly involved are ischemic injury viral infections associated neuropathies, chemotherapy-induced peripheral neuropathies, autoimmune disorders, traumatic origin, hereditary neuropathies, inflammatory disorders, and channelopathies. In CNS, angiogenesis is evident in inflammation of neurons and pain in bone cancer. The role of chemokines and cytokines is dualistic; their aggressive secretion produces detrimental effects, leading to neuropathic pain. However, whether the angiogenesis contributes and exists in neuropathic pain remains doubtful. In the present review, we elucidated summary of diverse mechanisms of neuropathic pain associated with angiogenesis. Moreover, an overview of multiple targets that have provided insights on the VEGF signaling, signaling through Tie-1 and Tie-2 receptor, erythropoietin pathway promoting axonal growth are also discussed. Because angiogenesis as a result of these signaling, results in inflammation, we focused on the mechanisms of neuropathic pain. These factors are mainly responsible for the activation of post-traumatic regeneration of the PNS and CNS. Furthermore, we also reviewed synthetic and herbal treatments targeting angiogenesis in neuropathic pain.

Mitochondrial Dysfunction: A Cellular and Molecular Hub in Pathology of Metabolic Diseases and Infection.

Mitochondria are semiautonomous doubly membraned intracellular components of cells. The organelle comprises of an external membrane, followed by coiled structures within the membrane called cristae, which are further surrounded by the matrix spaces followed by the space between the external and internal membrane of the organelle. A typical eukaryotic cell contains thousands of mitochondria within it, which make up 25% of the cytoplasm present in the cell. The organelle acts as a common point for the metabolism of glucose, lipids, and glutamine. Mitochondria chiefly regulate oxidative phosphorylation-mediated aerobic respiration and the TCA cycle and generate energy in the form of ATP to fulfil the cellular energy needs. The organelle possesses a unique supercoiled doubly stranded mitochondrial DNA (mtDNA) which encodes several proteins, including rRNA and tRNA crucial for the transport of electrons, oxidative phosphorylation, and initiating genetic repair processors. Defects in the components of mitochondria act as the principal factor for several chronic cellular diseases. The dysfunction of mitochondria can cause a malfunction in the TCA cycle and cause the leakage of the electron respiratory chain, leading to an increase in reactive oxygen species and the signaling of aberrant oncogenic and tumor suppressor proteins, which further alter the pathways involved in metabolism, disrupt redox balance, and induce endurance towards apoptosis and several treatments which play a major role in developing several chronic metabolic conditions. The current review presents the knowledge on the aspects of mitochondrial dysfunction and its role in cancer, diabetes mellitus, infections, and obesity.

Postulating the possible cellular signalling mechanisms of antibody drug conjugates in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world. Although the basic pathology of the disease is elucidated, it is difficult to restore or prevent the worsening of neurodegeneration and its symptoms. Antibody and small molecule-based approaches have been studied and are in study individually, but a combined approach like conjugation has not been performed to date. The conjugation between antibodies and drugs which are already used for Alzheimer's treatment or developed specifically for this purpose may have better efficacy and dual action in mitigating Alzheimer's disease. A probable mechanism for antibody-drug conjugates in Alzheimer's disease is discussed in the present review.

Phytochemicals targeting nitric oxide signaling in neurodegenerative diseases.

Neurodegenerative diseases are a set of diseases in which slow and progressive neuronal loss occurs. Nitric oxide (NO) as a neurotransmitter performs key roles in the stimulation and blockade of various inflammatory processes. Although physiological NO is necessary for protection against a variety of pathogens, reactive oxygen species-mediated oxidative stress induces inflammatory cascades and apoptosis. Activation of glial cells particularly astrocytes and microglia induce overproduction of NO, resulting in neuroinflammation and neurodegenerative disorders. Hence, inhibiting the overproduction of NO is a beneficial therapeutic approach for numerous neuroinflammatory conditions. Several compounds have been explored for the management of neurodegenerative disorders, but they have minor symptomatic benefits and several adverse effects. Phytochemicals have currently gained more consideration owing to their ability to reduce the overproduction of NO in neurodegenerative disorders. Furthermore, phytochemicals are generally considered to be safe and beneficial. The mechanisms of NO generation and their implications in neurodegenerative disorders are explored in this review article, as well as several newly discovered phytochemicals that might have NO inhibitory activity. The current review could aid in the discovery of new anti-neuroinflammatory drugs that can suppress NO generation, particularly during neuroinflammatory and neurodegenerative conditions.

Transfer learning for image classification using VGG19: Caltech-101 image data set.

Image classification is getting more attention in the area of computer vision. During the past few years, a lot of research has been done on image classification using classical machine learning and deep learning techniques. Presently, deep learning-based techniques have given stupendous results. The performance of a classification system depends on the quality of features extracted from an image. The better is the quality of extracted features, the more the accuracy will be. Although, numerous deep learning-based methods have shown enormous performance in image classification, still due to various challenges deep learning methods are not able to extract all the important information from the image. This results in a reduction in overall classification accuracy. The goal of the present research is to improve the image classification performance by combining the deep features extracted using popular deep convolutional neural network, VGG19, and various handcrafted feature extraction methods, i.e., SIFT, SURF, ORB, and Shi-Tomasi corner detector algorithm. Further, the extracted features from these methods are classified using various machine learning classification methods, i.e., Gaussian Naïve Bayes, Decision Tree, Random Forest, and eXtreme Gradient Boosting (XGBClassifier) classifier. The experiment is carried out on a benchmark dataset Caltech-101. The experimental results indicate that Random Forest using the combined features give 93.73% accuracy and outperforms other classifiers and methods proposed by other authors. The paper concludes that a single feature extractor whether shallow or deep is not enough to achieve satisfactory results. So, a combined approach using deep learning features and traditional handcrafted features is better for image classification.

COVID-19: Social distancing monitoring using faster-RCNN and YOLOv3 algorithms.

As of March 31, 2021, the Coronavirus COVID-19 was affecting 219 countries and territories worldwide, with approximately 129,574,017 confirmed cases and 2,830,220 death cases. Social isolation is the most reliable way to deal with this pandemic situation. Motivated by this notion, this paper proposes a deep learning-based technique for automating the task of monitoring social distancing using surveillance cameras. To separate humans from the background, the proposed system employs object detection models based on F-RCNN (Faster Region-based Convolutional Neural Networks) and YOLO (You Only Look Once) algorithms. In the COVID-19 environment, these models track the percentage of people who violate social distancing norms on a daily basis. The authors compared the performance of both models in experimental work using the MS COCO dataset. Many tests were carried out, and we discovered that YOLOv3 demonstrated efficient performance with balanced FPS (frames per second).

Focusing the pivotal role of nanotechnology in Huntington's disease: an insight into the recent advancements.

Neurodegeneration is the loss of neuronal capacity and structure over time which causes neurodegenerative disorders like Alzheimer, amyotrophic lateral sclerosis, Parkinson, and Huntington's disease (HD). This review is primarily concerned with HD, which was fully described by George Huntington in 1872. In developed countries, HD has become another common single-gene neurological disorder. Because of its autosomal dominant inheritance, the sickness affects both individuals and their families. Huntington disease has been recognized as a disorder that affects the complete body and brain in which the mutant huntingtin polyglutamine (polyQ) sequence is extensively increased and gets correlated to CAG trinucleotide which codes for glutamine (Q). These proteins have characteristics that produce apoptosis and dysfunction. HD is a lethal condition which needs an immediate diagnosis and treatment, and therefore, nanoparticle has come into sight out as opportunistic strategies for treatment of HD. Nanostructures have great potential to cross the blood brain barrier and also prevent breakdown of active molecule and reduces the drug toxicity. This review explains the distinguishing symptoms, genetics, and stages during the development of Huntington's disease, and also provides an overview of HD with an emphasis on its epidemiology, pathogenesis, and management. This review focuses on the latest studies on nanotechnology-related technologies, i.e., magnetic nanoparticle, solid lipid nanoparticle, and polymeric nanoparticle for Huntington's disease treatment. The pioneering patents and in-progress clinical trials related to Huntington's disease has also been summarized in this review.

Role of matrix metalloproteinase in wound healing.

Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a vital role in the restoration of damaged skin. Through mediating various cellular events such as angiogenesis and vasodilation, MMPs are very crucial for the mechanism of wound healing. These enzymes are endopeptidases that are reliant on zinc which are concealed through the extracellular matrix (ECM). MMPs have different targets in different phases of wound healing through which they are capable of promoting timely healing in the body. This review discusses all the possible role of MMPs and their inhibitors that are involved during every step of the wound healing process. This review highlights the latest advances in the respective field about the regulation and mediation of MMPs in human skin and how these studies can be applied to other branches of medical sciences as well. Published papers were searched via MEDLINE, PubMed and MDPI from the available peer reviewed journals. Research done in the past suggests that active MMPs are involved in the healing progression of the wounds or they have a positive effect towards healing of wounds. Present studies in the relative field will further enhance the knowledge about enzymes working along with their inhibitors. These studies will help in a way to resolve some of the parameters that are necessary for modulating them either positively or negatively.

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.

Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies.

Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis.

Decrypting the potential role of α-lipoic acid in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases with motor disturbances, cognitive decline, and behavioral impairment. It is characterized by the extracellular aggregation of amyloid-ß plaques and the intracellular accumulation of tau protein. AD patients show a cognitive decline, which has been associated with oxidative stress, as well as mitochondrial dysfunction. Alpha-lipoic acid (α-LA), a natural antioxidant present in food and used as a dietary supplement, has been considered a promising agent for the prevention or treatment of neurodegenerative disorders. Despite multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects, to date only a few studies have examined its effects in humans. Studies performed in animal models of memory loss associated with aging and AD have shown that α-LA improves memory in a variety of behavioral paradigms. Furthermore, molecular mechanisms underlying α-LA effects have also been investigated. Accordingly, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies. In addition, it has been shown that α-LA reverses age-associated loss of neurotransmitters and their receptors. The review article aimed at summarizing and discussing the main studies investigating the neuroprotective effects of α-LA on cognition as well as its molecular effects, to improve the understanding of the therapeutic potential of α-LA in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with α-LA.

Exploring Sonic Hedgehog Cell Signaling in Neurogenesis: Its Potential Role in Depressive Behavior.

Depression is the most prevalent form of neuropsychiatric disorder affecting all age groups globally. As per the estimation of the World Health Organization (WHO), depression will develop into the foremost reason for disability globally by the year 2030. The primary neurobiological mechanism implicated in depression remains ambiguous; however, dysregulation of molecular and signaling transductions results in depressive disorders. Several theories have been developed to explain the pathogenesis of depression, however, none of them completely explained all aspects of depressive-pathogenesis. In the current review, we aimed to explore the role of the sonic hedgehog (Shh) signaling pathway in the development of the depressive disorder and its potential as the therapeutic target. Shh signaling has a crucial function in neurogenesis and neural tube patterning during the development of the central nervous system (CNS). Shh signaling performs a basic function in embryogenesis and hippocampal neurogenesis. Moreover, antidepressants are also known to enhance neurogenesis in the hippocampus, which further suggests the potential of Shh signaling. Furthermore, there is decreased expression of a glioma-associated oncogene (Gli1) and Smoothened (Smo) in depression. Moreover, antidepressants also regulate brain-derived neurotrophic factor (BDNF) and wingless protein (Wnt) signaling, therefore, Shh may be implicated in the pathogenesis of the depressive disorder. Deregulation of Shh signaling in CNS results in neurological disorders such as depression.

Face mask detection using YOLOv3 and faster R-CNN models: COVID-19 environment.

There are many solutions to prevent the spread of the COVID-19 virus and one of the most effective solutions is wearing a face mask. Almost everyone is wearing face masks at all times in public places during the coronavirus pandemic. This encourages us to explore face mask detection technology to monitor people wearing masks in public places. Most recent and advanced face mask detection approaches are designed using deep learning. In this article, two state-of-the-art object detection models, namely, YOLOv3 and faster R-CNN are used to achieve this task. The authors have trained both the models on a dataset that consists of images of people of two categories that are with and without face masks. This work proposes a technique that will draw bounding boxes (red or green) around the faces of people, based on whether a person is wearing a mask or not, and keeps the record of the ratio of people wearing face masks on the daily basis. The authors have also compared the performance of both the models i.e., their precision rate and inference time.

Focus on Multi-targeted Role of Curcumin: a Boon in Therapeutic Paradigm.

Curcumin is a polyphenolic compound that exhibited good anticancer potential against different types of cancers through its multi-targeted effect like the termination of cell proliferation, inflammation, angiogenesis, and metastasis, thereby acting as antiproliferative and cytotoxic in nature. The present review surveys the various drug combination tried with curcumin or its synthetic analogues and also the mechanism by which curcumin potentiates the effect of almost every drug. In addition, this article also focuses on aromatherapy which is gaining much popularity in cancer patients. After thoroughly studying several articles on combination therapy of curcumin through authenticated book chapters, websites, research, and review articles available at PubMed, ScienceDirect, etc., it has been observed that multi-targeted curcumin possess enormous anticancer potential and, with whatever drug it is given in combination, has always resulted in enhanced effect with reduced dose as well as side effects. It is also capable enough in overcoming the problem of chemoresistance. Besides this, aromatherapy also proved its potency in reducing cancer-related side effects. Combining all the factors together, we can conclude that combination therapy of drugs with curcumin should be explored extensively. In addition, aromatherapy can be used as an adjuvant or supplementary therapy to reduce the cancer complications in patients.

Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics.

The role of mitochondria in the apoptosis signaling cell death pathway is regulated by extrinsic and intrinsic pathway, encompassing multiple components like the Bcl-2 family of proteins, death receptors, caspases, Smac/DIABLO, IAPs, Omi/HtrA2 and cytochrome c. These entities serve as effective molecular targets for numerous drugs targeting mitochondrial apoptotic pathways, mainly emphasizing oncology therapeutics. Defective apoptosis is an acquired hallmark of cancer cells, which promotes the establishment of apoptosis-targeting anti-cancer drugs in cancer treatment. The review provides an overview of the Bcl-2 inhibiting, IAPs antagonizing, caspase inhibiting and BH3 mimicking actions, mediated by anti-cancer drugs, rendering beneficial outcomes in different forms of cancer. The authors elaborate on the significance of synthetic and natural agents, targeting the mitochondrial apoptotic pathway, in ameliorating tumor cell growth in the body, and the specificity and effectiveness of these agents, motivating the researchers to explore mitochondrial apoptosis targeting of anti-tumor drugs of both herbal and synthetic origin. Thus, the review aims to predict this dynamic approach in oncology, simultaneously highlighting the challenges and future prospects, providing an opportunity to the experts to "go over with a fine tooth comb" in understanding this "programmed cell death pathway", and establishing reliability and accuracy of this therapeutic paradigm in the upcoming future.