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result(s) for
"Shrivastava, Neeraj"
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Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system
by
Shrivastava, Neeraj
,
Jain, Sudhir Kumar
,
Hari, Sharath Kumar
in
Biomedical and Life Sciences
,
Biomedicine
,
Pharmaceutical Sciences/Technology
2023
Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood–brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as “smart drug carriers,” allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.
Graphical abstract
Journal Article
Breast tumor detection and classification based on density
2020
Breast cancer is the most widely disease in women and is considered one of the biggest causes of death in women. Early detection, classification, and diagnosis of this cancer are essential to reduce the death cases. The efficiency of the diagnosis of breast cancer depends on the accuracy of the segmentation of the tumor and its classification. Before the segmentation of mammogram images, it is necessary to extract the Region of Interest (ROI) because it can assume a significant job in the efficiency of tumor detection. In this study, the method of automatic extraction of ROI from the mammogram image is presented. After that, the preprocessing of both mammogram and MR images has been done which removes the noise and enhances the contrast of the images. On the processed images, segmentation of tumors from mammograms as well as Magnetic Resonance Imaging (MRI) breast images has been performed using automatic seed point extraction and threshold calculation in Seeded Region Growing (SRG). After the successful detection of breast tumor area, classification of the tumor as benign or malignant has been done. The test was performed on three publicly available data sets; RIDER breast MR Images, Mammographic Image Analysis Society (MIAS), and Digital Database for Screening Mammography (DDSM). The test showed that classification accuracy is better than previously accessible cutting edge techniques, which is 91.4%. The proposed method not only detects the shape and size of the tumor from both mammograms and MR Images but also efficiently classifies the tumor as benign or malignant.
Journal Article
High level of persister frequency in clinical staphylococcal isolates
by
Pandey, Shanti
,
Shrivastava, Neeraj
,
Singh, Anjana
in
Anti-Bacterial Agents - pharmacology
,
Anti-Bacterial Agents - therapeutic use
,
Antibiotic tolerance
2022
Background
Staphylococcus aureus
is a notorious human pathogen that causes often lethal systemic conditions that are mostly medical device associated biofilm infections. Similarly, coagulase negative staphylococci are emerging as leading pathogen for nosocomial infections owing to their ability to form biofilm on implanted medical equipment. Chronic in nature, these infections are difficult to treat. Such recalcitrance of these infections is caused mainly due to the presence of persister cells, which exhibit transient yet extreme tolerance to antibiotics. Despite tremendous clinical significance, there is lack of studies on persister cells formation among clinical bacterial isolates. Considering the importance of factors influencing persister formation, in this study, we evaluate the association of antibiotic tolerance with biofilm production, antibiotic stress, growth phase, specimen type, and dependency on staphylococcal species. Biofilm formation was detected among 375 clinical staphylococcal isolates by quantitative tissue culture plate method (TCP) and
icaAD
genes by genotypic method. The antibiotic susceptibility was determined by Kirby Bauer disc diffusion method while minimum inhibitory concentration values were obtained by agar dilution method. Persister cells were measured in the susceptible staphylococcal isolates in the presence of clinically relevant antibiotics.
Results
In the study, 161 (43%)
S. aureus
and 214 (57%) coagulase negative staphylococci (CNS) were isolated from different clinical samples. TCP method detected biofilm production in 84 (52.2%)
S. aureus
and 90 (42.1%) CNS isolates. The genotypic method detected
icaAD
genes in 86 (22.9%) isolates. Majority (> 90%) of both the biofilm producers and non-producers were sensitive to chloramphenicol and tetracycline but were resistant to penicillin. Interestingly, all isolates were sensitive to vancomycin irrespective of biofilm production. While high persister frequency was observed among all staphylococci isolates in the stationary growth phase, the persister frequency in exponential growth phase was statistically high among isolates possessing
icaAD
genes compared to
icaAD
negative isolates.
Conclusion
The research findings provide strong evidence that the clinical staphylococcal isolates exhibit extreme antibiotic tolerance suggesting their causal link with treatment failures. Understanding the factors influencing the formation and maintenance of persister cells are of utmost important aspect to design therapeutics and control recalcitrant bacterial infections.
Journal Article
Evaluation of methods to detect in vitro biofilm formation by staphylococcal clinical isolates
2018
Objective
Staphylococcus genus comprising both
Staphylococcus aureus
and coagulase negative staphylococci (CoNS) are widely distributed in nature and can infect diversity of hosts. Indeed, staphylococci are the major pathogens causing biofilm associated infections caused by contaminated hospital indwelling devices. These infections are persistent in nature being highly refractory to various stresses including antibiotics. Implementation of efficient diagnostic techniques for the biofilm production would help minimize the disease burden. Thus, early detection of pathogenic strains producing biofilms warrant the utmost importance in diagnostic laboratories especially in resource limited settings.
Result
Among 375 isolates collected from different clinical specimens, 214 (57%) were identified as coagulase negative staphylococci and 161 (43%)
S. aureus.
Detection of
In
-
vitro
biofilm formation in these isolates were carried out by three commonly used phenotypic assays and a genotypic assay. While evaluating the results, tissue-culture method with supplemented glucose and sucrose showed the best correlation with the results of genotypic assay.
Journal Article
NHCDRA: a non-uniform hierarchical clustering with dynamic route adjustment for mobile sink based heterogeneous wireless sensor networks
by
Shrivastava, Neeraj
,
Jain, Shushant Kumar
,
Verma, Rahul Kumar
in
Cluster analysis
,
Clustering
,
Communications Engineering
2021
In wireless sensor networks (WSNs), various routing protocols have been proposed based on clustering to achieve energy efficiency. The performance of such routing protocols can further be improved by deploying heterogeneous sensor nodes since responsibilities can be divided among different sensor nodes according to their heterogeneity. In this paper, we propose a novel non-uniform hierarchical clustering with dynamic route adjustment scheme, termed as NHCDRA, for heterogeneous WSNs considering two mobile sinks moving around the periphery of the sensor field. NHCDRA divides the sensor field into several non-uniform sized hierarchical clusters. The size of boundary clusters (near to the sink’s mobility path) is kept relatively large to accommodate more number of sensor nodes so that the responsibilities of cluster heads can be rotated efficiently to distribute the load. Furthermore, a set of dynamic route adjustment rules are defined to manage the routing paths as a consequence of mobility of the sinks. These rules reduce the overhead of route adjustment as well as ensure data delivery to the sink in minimal number of hops. Simulation results show that NHCDRA significantly reduces the data delivery delay and improves network lifetime when compared with state-of-the-art.
Journal Article
Phenotypic and genotypic characterization of biofilm producing clinical coagulase negative staphylococci from Nepal and their antibiotic susceptibility pattern
by
Pandey, Shanti
,
Shrivastava, Neeraj
,
Singh, Anjana
in
Antibacterial agents
,
Antibiotic susceptibility
,
Antibiotics
2021
Background
Coagulase-negative staphylococci (CNS) survive as commensals of skin, anterior nares and external canals of human and were regarded as non-infectious pathogens. However, they are emerging as a major cause of nosocomial infectious due to their ability to form biofilms and high resistance to several classes of antibiotics. This study examines the biofilm forming abilities of 214 clinical CNS isolates using phenotypic and genotypic methods, and determines their antibiotic susceptibility patterns.
Methods
A total of 214 clinical isolates collected from different clinical samples were identified as CNS and their antibiotic susceptibility determined by CLSI guidelines. The biofilm forming ability of all isolates was determined by three phenotypic methods; Congo red agar (CRA) method, tube adherence method (TM) and tissue culture plate (TCP) method and by genotypic method for the detection of
icaAD
genes.
Results
Among all the isolates,
S. epidermidis
(57.5%) was found the most frequently, followed by
S. saprophyticus
(18.7%)
, S. haemolyticus
(11.2%)
, S. hominis
(7%), and
S. capitis
(5.6%). Antibiotic susceptibility pattern demonstrated 91.6% isolates were resistant to penicillin and 66.8% to cefoxitin while 91.1% isolates were susceptible to chloramphenicol. Constitutive and inducible clindamycin resistant phenotype as measured by D-test was seen among 28% and 14.5% of isolates respectively. Tissue culture plate method detected biofilm production in 42.1% isolate followed by 31.8% through tube method while 20.1% isolates were found to produce slime in Congo red agar method. The genotypic assay revealed presence of
icaA
and
icaD
genes in 19.2% isolates.
Conclusion
The study shows a high prevalence of biofilm formation and inducible clindamycin resistance in CNS isolates, indicating the importance of
in-vitro
biofilm production test and D-test in routine laboratory diagnostics. Implementation of efficient diagnostic techniques for detection of biofilm production in clinical samples can help manage staphylococcal infections and minimize risks of treatment failures in hospitals.
Journal Article
Harnessing Potential of ω-3 Polyunsaturated Fatty Acid with Nanotechnology for Enhanced Breast Cancer Therapy: A Comprehensive Investigation into ALA-Based Liposomal PTX Delivery
by
Shrivastava, Neeraj
,
Sonkar, Archana
,
Kaithwas, Gaurav
in
cancer
,
Cancer therapies
,
cell culture
2024
Our hypothesis posited that incorporating alpha-linolenic acid (ALA) into liposomes containing Paclitaxel (PTX) could augment cellular uptake, decrease the therapeutic dosage, and alleviate PTX-related side effects. Our investigation encompassed characterization of the liposomal formulation, encompassing aspects like particle size, surface morphology, chemical structure, drug release kinetics, and stability. Compatibility studies were performed through Fourier transform infrared spectroscopy (FTIR). By utilizing the Box–Behnken design (BBD), we developed ALA-based liposomes with satisfactory particle size and entrapment efficiency. It is noteworthy that ALA incorporation led to a slight increase in particle size but did not notably affect drug entrapment. In vitro drug release assessments unveiled a sustained release pattern, with ALA-PTX liposomes demonstrating release profiles comparable to PTX liposomes. Morphological examinations confirmed the spherical structure of the liposomes, indicating that substituting ALA with phosphatidylcholine did not alter the physicochemical properties. Cellular uptake investigations showcased enhanced uptake of ALA-based liposomes in contrast to PTX liposomes, likely attributed to the heightened fluidity conferred by ALA. Efficacy against MCF-7 cells demonstrated concentration-dependent reductions in cell viability, with ALA-PTX liposomes exhibiting the lowest IC50 value. Morphological analysis confirmed apoptotic changes in cells treated with all formulations, with ALA-PTX liposomes eliciting more pronounced changes, indicative of enhanced anticancer efficacy.
Journal Article
Virtual Grid-Based Routing for Query-Driven Wireless Sensor Networks
by
Shrivastava, Neeraj
,
Hashmi, Mohammad Farukh
,
Salunke, Sharad
in
Data collection
,
Data transmission
,
Energy
2023
In the context of query-driven wireless sensor networks (WSNs), a unique scenario arises where sensor nodes are solicited by a base station, also known as a sink, based on specific areas of interest (AoIs). Upon receiving a query, designated sensor nodes are tasked with transmitting their data to the sink. However, the routing of these queries from the sink to the sensor nodes becomes intricate when the sink is mobile. The sink’s movement after issuing a query can potentially disrupt the performance of data delivery. To address these challenges, we have proposed an innovative approach called Query-driven Virtual Grid-based Routing Protocol (VGRQ), aiming to enhance energy efficiency and reduce data delivery delays. In VGRQ, we construct a grid consisting of square-shaped virtual cells, with the number of cells matching the count of sensor nodes. Each cell designates a specific node as the cell header (CH), and these CHs establish connections with each other to form a chain-like structure. This chain serves two primary purposes: sharing the mobile sink’s location information and facilitating the transmission of queries to the AoI as well as data to the sink. By employing the VGRQ approach, we seek to optimize the performance of query-driven WSNs. It enhances energy utilization and reduces data delivery delays. Additionally, VGRQ results in ≈10% and ≈27% improvement in energy consumption when compared with QRRP and QDVGDD, respectively.
Journal Article
Prevalence and characterization of Panton-Valentine leukocidin-positive Staphylococcus aureus in bovine milk in Jabalpur district of Madhya Pradesh, India
by
Shrivastava, Neeraj
,
Shrivastav, Arpita
,
Nayak, Anju
in
Antimicrobial agents
,
bovine milk
,
Cow's milk
2018
The study aimed to investigate the Panton-Valentine leukocidin (PVL)-positive
in bovine milk due to its public health significance.
A total of 400 milk samples of bovines taken from different dairy farms and outlets of Jabalpur were screened for the
and methicillin-resistant
(MRSA). The strains were tested for the PVL gene and antimicrobial sensitivity toward 10 different classes of antimicrobial agents. The PVL-positive
strains were further characterized by staphylococcal protein A or
typing.
The prevalence of PVL-positive
was 10.53%. All the isolates positive for the PVL were resistant to methicillin, while the methicillin-sensitive
isolates were negative for the PVL. Five different
types were found.
The presence of PVL-positive MRSA in bovine milk close to consumer poses a potential public health risk to the community.
Journal Article
Genomic and Transcriptomic Characterization of Alternaria alternata during Infection
by
Jiao, Chen
,
Zhou, Xianqi
,
Cao, Yuwei
in
agronomy
,
Alternaria alternata
,
Alternaria brown spot
2023
Host-pathogen interactions are the result of the continuously evolving dynamics of the genomic interphases between pathogens and the host plants. Alternaria brown spot (ABS) caused by the pathogen Alternaria alternata is a serious threat to tangerine production. Although recent studies have made significant advances in the characterization of A. alternata virulence factors, a gap exists in the regulation of virulent genes throughout the course of A. alternata infection on host plants. To gain a better understanding of the dynamic defense transcriptome in Alternaria alternata during Infection, we performed a comparative transcriptome approach. After inoculation on citrus, we found that 2142, 1964, 2359 genes were up-regulated, and 1948, 1434, 1996 genes were down-regulated at 12 hours-post-inoculation (hpi), 24 hpi and 48 hpi, respectively. Among these genes, 1333 genes were up-regulated at three time points, and 1054 genes were down-regulated, indicating that most of the differentially expressed genes at the early stage of infection tended to remain differentially expressed at the later stage of infection. In addition to the genes that are known to be part of the infection network in plant-pathogen interactions, many novel genes related to plant-pathogen interaction were identified. Interestingly, our results indicate that A. alternata is able to rapidly alter its gene expression pattern during infection process, which is vital for the successful colonization of the pathogen. Moreover, this rapid alteration of gene expression is likely to be an adaptive mechanism, enabling the pathogen to quickly respond to any changes in the environment and adapt to the host’s defense system. This ability to modify gene expression quickly in the face of environmental changes could play a critical role in the successful establishment of infection. RT-qPCR analysis confirmed that the expression pattern of nine randomly selected genes from the peroxisome pathway were consistent with the RNA-seq data. Our study provided a comprehensive study of the expression of genes during A. alternata infection of citrus, which may facilitate the understanding of host-plant interactions in A. alternata.
Journal Article