Computational Frontiers in Aptamer-Based Nanomedicine for Precision Therapeutics: A Comprehensive Review.

In the rapidly evolving landscape of nanomedicine, aptamers have emerged as powerful molecular tools, demonstrating immense potential in targeted therapeutics, diagnostics, and drug delivery systems. This paper explores the computational features of aptamers in nanomedicine, highlighting their advantages over antibodies, including selectivity, low immunogenicity, and a simple production process. A comprehensive overview of the aptamer development process, specifically the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, sheds light on the intricate methodologies behind aptamer selection. The historical evolution of aptamers and their diverse applications in nanomedicine are discussed, emphasizing their pivotal role in targeted drug delivery, precision medicine and therapeutics. Furthermore, we explore the integration of artificial intelligence (AI), machine learning (ML), Internet of Things (IoT), Internet of Medical Things (IoMT), and nanotechnology in aptameric development, illustrating how these cutting-edge technologies are revolutionizing the selection and optimization of aptamers for tailored biomedical applications. This paper also discusses challenges in computational methods for advancing aptamers, including reliable prediction models, extensive data analysis, and multiomics data incorporation. It also addresses ethical concerns and restrictions related to AI and IoT use in aptamer research. The paper examines progress in computer simulations for nanomedicine. By elucidating the importance of aptamers, understanding their superiority over antibodies, and exploring the historical context and challenges, this review serves as a valuable resource for researchers and practitioners aiming to harness the full potential of aptamers in the rapidly evolving field of nanomedicine.

Microbial exopolysaccharides: Unveiling the pharmacological aspects for therapeutic advancements.

Microbial exopolysaccharides (EPSs) have emerged as a fascinating area of research in the field of pharmacology due to their diverse and potent biological activities. This review paper aims to provide a comprehensive overview of the pharmacological properties exhibited by EPSs, shedding light on their potential applications in various therapeutic areas. The review begins by introducing EPSs, exploring their various sources, significance in microbial growth and survival, and their applications across different industries. Subsequently, a thorough examination of the pharmaceutical properties of microbial EPSs unveils their antioxidant, immunomodulatory, antimicrobial, antidepressant, antidiabetic, antiviral, antihyperlipidemic, hepatoprotective, anti-inflammatory, and anticancer activities. Mechanistic insights into how different EPSs exert these therapeutic effects have also been discussed in this review. The review also provides comprehensive information about the monosaccharide composition, backbone, branches, glycosidic bonds, and molecular weight of pharmacologically active EPSs from various microbial sources. Furthermore, the factors that can affect the pharmacological activities of EPSs and approaches to improve the EPSs' pharmacological activity have also been discussed. In conclusion, this review illuminates the immense pharmaceutical promise of microbial EPS as versatile bioactive compounds with wide-ranging therapeutic applications. By elucidating their structural features, biological activities, and potential applications, this review aims to catalyze further research and development efforts in leveraging the pharmaceutical potential of microbial EPS for the advancement of human health and well-being, while also contributing to sustainable and environmentally friendly practices in the pharmaceutical industry.

Assessment of agriwaste derived substrates to grow ornamental plants for constructed wetland.

Burning of surplus residues in agricultural fields is a common practice in many countries of the world. This practice adds emissions into the atmosphere and results in the loss of essential plant nutrients, hence, there is a need for developing technologies for the sustainable management of agri-residues. Constructed wetlands offer excellent nature-based, low-cost green technologies for the treatment of wastewater using surplus agricultural residues as wetland substrates to grow ornamental plants as a source of income. This study was conducted to investigate the use of agricultural residues and biochar as substrates to grow ornamental plants in constructed wetlands. Four ornamental plants (Canna Indica, Gerbera jamesonii, Liliumwallichianum, and Tagetes erecta) were grown in six different substrate combinations for 120 days. Data on plant growth parameters were collected for each plant and compared to select the best substrate combination. Canna Indica and Lilium wallichianum resulted in significantly higher growth and nutrient uptake (P<0.001) with the substrate of 15% rice straw, 80% soil, 5% biochar (T4), and 25% sugarcane bagasse, 70% soil, 5% biochar (T5) compared to other plants. The result concluded that agricultural waste-derived substrates are viable alternatives having fertilizing effects with the potential for nutrient recovery. The present study provides an alternative approach to utilize agricultural waste sustainably to grow ornamental plants in the constructed wetland which reduces the overall cost of the wetland unit making it more cost-efficient.

Evaluation of quality of life in posttreatment upper aerodigestive tract cancer patients.

Background: Cancers of the upper aerodigestive tract constitute approximately 4% of all malignancies. Posttreatment cancer patient faces serious adversities that affect the quality of life. Out of the various scales available to measure the quality of life, we chose the quality of life-oral cancer (QOL-OC), which was developed and evaluated by Nie et al. in 2018. Aims and Objectives: The aim of our study was to assess the quality of life in posttreatment upper aerodigestive tract cancer patients in a tertiary care center and also to check the reliability and validity of the questionnaire QOL-OC. Methodology: We communicated with 89 patients who were pathologically tested positive for upper aero digestive tract cancer from January 2019 to December 2019. Results: The most prevalent adversity was found to be altered salivary flow, followed by diet and difficulty while eating. The QOL-OC was found to be a highly valid and reliable questionnaire. Conclusion: The study points out regarding the prevalence of various adversities in post treatment cancer patients, a discussion has also been made suggesting the importance of multidisciplinary approach that should be provided in such patients. Finally, the study also concludes regarding the generalizability of the questionnaire QOL-OC.

MERS virus spike protein HTL-epitopes selection and multi-epitope vaccine design using computational biology.

MERS-CoV, a zoonotic virus, poses a serious threat to public health globally. Thus, it is imperative to develop an effective vaccination strategy for protection against MERS-CoV. Immunoinformatics and computational biology tools provide a faster and more cost-effective strategy to design potential vaccine candidates. In this work, the spike proteins from different strains of MERS-CoV were selected to predict HTL-epitopes that show affinity for T-helper MHC-class II HTL allelic determinant (HLA-DRB1:0101). The antigenicity and conservation of these epitopes among the selected spike protein variants in different MERS-CoV strains were analyzed. The analysis identified five epitopes with high antigenicity: QSIFYRLNGVGITQQ, DTIKYYSIIPHSIRS, PEPITSLNTKYVAPQ, INGRLTTLNAFVAQQ and GDMYVYSAGHATGTT. Then, a multi-epitope vaccine candidate was designed using linkers and adjuvant molecules. Finally, the vaccine construct was subjected to molecular docking with TLR5 (Toll-like receptor-5). The proposed vaccine construct had strong binding energy of -32.3 kcal/mol when interacting with TLR5.Molecular dynamics simulation analysis showed that the complex of the vaccine construct and TLR5 is stable. Analysis using in silico immune simulation also showed that the prospective multi-epitope vaccine design had the potential to elicit a response within 70 days, with the immune system producing cytokines and immunoglobulins. Finally, codon adaptation and in silico cloning analysis showed that the candidate vaccine could be expressed in the Escherichia coli K12 strain. Here we also designed support vaccine construct MEV-2 by using B-cell and CD8+ CTL epitopes to generate the complete immunogenic effect. This study opens new avenues for the extension of research on MERS vaccine development.Communicated by Ramaswamy H. Sarma.

Expanding role of ribosome-inactivating proteins: From toxins to therapeutics.

Ribosome-inactivating proteins (RIPs) are toxic proteins with N-glycosidase activity. RIPs exert their action by removing a specific purine from 28S rRNA, thereby, irreversibly inhibiting the process of protein synthesis. RIPs can target both prokaryotic and eukaryotic cells. In bacteria, the production of RIPs aid in the process of pathogenesis whereas, in plants, the production of these toxins has been attributed to bolster defense against insects, viral, bacterial and fungal pathogens. In recent years, RIPs have been engineered to target a particular cell type, this has fueled various experiments testing the potential role of RIPs in many biomedical applications like anti-viral and anti-tumor therapies in animals as well as anti-pest agents in engineered plants. In this review, we present a comprehensive study of various RIPs, their mode of action, their significance in various fields involving plants and animals. Their potential as treatment options for plant infections and animal diseases is also discussed.

Synthesis of Carvacrol Derivatives as Potential New Anticancer Agent against Lung Cancer.

Lung cancer remains a major public health concern among all cancer diseases due to the toxicity and side-effects of the available commercially synthesized drugs. Natural product-derived synthesized anticancer drugs are now of promising interest to fight against cancer death. Carvacrol is a major component of most essential oil-bearing plants with potential pharmacological activity, especially against various cancer cell lines. Among the other organometallic compounds, copper complexes have been reported to be effective anticancer agents against various cancer cell lines, especially lung and leukemia cancers, due to the nontoxic nature of copper in normal cells since it is an endogenic metal. In this study, we synthesized three carvacrol derivatives, i.e., carvacrol aldehyde, Schiff base, and copper-Schiff base complex, through an established synthesis protocol and characterized the synthesized product using various spectroscopic techniques. The synthesized derivatives were evaluated for in vitro cytotoxic activity against different cancer cell lines, including human lung cancer (A549) and human fibroblast (BALB-3T3). Our findings showed that the copper-Schiff base complex derived from carvacrol inhibited the proliferation and migration of the A549 cell lines in a dose-dependent manner. This activity might be due to the inhibition of cell proliferation and migration at the G2/M cell-cycle phase, as well as apoptosis, possibly through the activation of the mitochondrial apoptotic pathway. To our knowledge, this is the first report on the activity of the copper-Schiff base complex of carvacrol against A549 cell lines. Our result highlights that a new synthesized copper complex from carvacrol could be a novel potential drug in the treatment of lung cancer.

Structural insights into the amino acid usage variations in the profilin gene family.

Profilin protein is present ubiquitously in all forms of life and is allied with allergic responses among atopic individuals. In addition to this, profilins from various food sources are also associated with IgE cross-reactivity and are thus classified as pan-allergens. The present study unravels the physicochemical basis of differential amino acid usage patterns observed in the profilin gene family. Correspondence analysis based on amino acid usage of allergen and non-allergen profilins revealed discrete clusters among them, signifying differential patterns of amino acid usage. The amino acids, namely methionine, proline, histidine, glutamine, glutamic acid, tryptophan and glycine were found to be more frequently utilised by the allergen profilins compared to the non-allergens. Correlation analysis revealed that physicochemical features like protein disorder, trypsin digestion and solubility differed significantly among the allergen and non-allergen profilins, thus supporting the observations from correspondence analysis. In addition, comprehensive sequence analysis revealed that the allergen profilins possess conserved motifs which may correlate with their distinct physicochemical features. An in-depth structural analysis revealed that the over-represented amino acids in allergen profilins have a propensity of being exposed on the surface, which may be attributed to their distinct allergenic characteristics. The distinguished physicochemical features observed among allergens and non-allergens can be employed as descriptors to develop machine learning-based allergenicity prediction models.

Role of Natural Killer Cells during Pregnancy and Related Complications.

A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.

A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents.

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

Base Composition and Host Adaptation of the SARS-CoV-2: Insight From the Codon Usage Perspective.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly all over the world and has raised grave concern globally. The present research aims to conduct a robust base compositional analysis of SARS-CoV-2 to reveal adaptive intricacies to the human host. Multivariate statistical analysis revealed a complex interplay of various factors including compositional constraint, natural selection, length of viral coding sequences, hydropathicity, and aromaticity of the viral gene products that are operational to codon usage patterns, with compositional bias being the most crucial determinant. UpG and CpA dinucleotides were found to be highly preferred whereas, CpG dinucleotide was mostly avoided in SARS-CoV-2, a pattern consistent with the human host. Strict avoidance of the CpG dinucleotide might be attributed to a strategy for evading a human immune response. A lower degree of adaptation of SARS-CoV-2 to the human host, compared to Middle East respiratory syndrome (MERS) coronavirus and SARS-CoV, might be indicative of its milder clinical severity and progression contrasted to SARS and MERS. Similar patterns of enhanced adaptation between viral isolates from intermediate and human hosts, contrasted with those isolated from the natural bat reservoir, signifies an indispensable role of the intermediate host in transmission dynamics and spillover events of the virus to human populations. The information regarding avoided codon pairs in SARS-CoV-2, as conferred by the present analysis, promises to be useful for the design of vaccines employing codon pair deoptimization based synthetic attenuated virus engineering.

Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: An in silico investigation.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an in silico approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve Clerodendrum species against the imperative spike protein, main protease enzyme Mpro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski's rule of five and Veber's rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol in vitro and in vivo towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19.Communicated by Ramaswamy H. Sarma.

An Integrated Strategy for Nutraceuticals from Haematoccus pluvialis: From Cultivation to Extraction.

The aim of this study was to develop an effective integrated cultivation system for Haematococcus pluvialis as a source of bioactive compounds such as astaxanthin, lutein, proteins, and fatty acids (FAs). The Chlorophyta H. pluvialis was cultivated in a vertical bubble column photobioreactor (VBC-PBR) under batch mode, allowing switching from green to red phase for astaxanthin induction. The combined effect of light intensity and nutrients on bioactive compound formation was investigated. Results showed that growth under lower nutrients availability and light intensity led to a higher concentration of biomass. Growth under high light intensity with an appropriate concentration of nitrate, sulfate, phosphate and magnesium led to ~85% and ~58% higher production of total carotenoids and fatty acids, respectively. Under high stress conditions, ~90% nitrate and phosphate consumption were observed.

Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta.

Preeclampsia (PE) is a serious pregnancy complication, affecting about 5-7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks' gestation and, if left untreated, can lead to serious complications and lifelong disabilities-even death-in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also called soluble fms-like tyrosine kinase-1 (sFlt-1), are believed to be among the primary pathologies associated with PE. sFlt-1 is produced mainly in the placenta during pregnancy and acts as a decoy receptor, binding to free VEGF (VEGF-A) and placental growth factor (PlGF), resulting in the decreased bioavailability of each to target cells. Despite the pathogenic effects of increased sFlt-1 on the maternal vasculature, recent studies from our laboratory and others have strongly indicated that the increase in sFlt-1 in PE may fulfill critical protective functions in preeclamptic pregnancies. Thus, further studies on the roles of sFlt-1 in normal and preeclamptic pregnancies are warranted for the development of therapeutic strategies targeting VEGF signaling for the treatment of PE. Another impediment to the treatment of PE is the lack of suitable methods for delivery of cargo to placental cells, as PE is believed to be of placental origin and most available therapies for PE adversely impact both the mother and the fetus. The present review discusses the pathogenesis of PE, the complex role of sFlt-1 in maternal disease and fetal protection, and the recently developed placenta-targeted drug delivery system for the potential treatment of PE with candidate therapeutic agents.

Phytochemicals enriched in spices: a source of natural epigenetic therapy.

Metabolic disorders are increasing at an alarming rate due to the stressful lifestyle and inappropriate diet schedule. The unorganized habits influence multiple epigenetic mechanisms like DNA methylation, histone post-translational modifications and miRNA expression. These epigenetic modifications are reversible in nature and regulate gene expression in response to external stimuli without altering the DNA sequence. Dietary herbs are enriched in various phytochemicals which additionally provide nutrition and health benefits; and are known to target these epigenetic gene regulatory mechanisms. They have been in use since human civilization for their health-promoting effects. Culinary spices and condiments which are generally used to enhance the taste of food are rich repositories of many phytochemicals which provides them their unique aroma. Considerable attention has been given to "Nutri-epigenetics" nowadays, with a focus on evaluating the potential of phytochemicals to regulate/neutralize various epigenetic modifications. This article aims at highlighting the epigenetic regulatory roles of phytochemicals present in condiments and spices with considerable health benefits.

Identification through dental age estimation in skeletal remains of a child.

The analysis of skeletal remains opens the portal of scientific truth that enables the justice system to discover the facts and circumstances surrounding criminal acts. There is definite role of forensic odontology in identification and determination of dental age of skeletal remains (mandible), especially when visual identification and fingerprints cannot be used. Here, we present a case of a missing boy whose skeletal remains were recovered from a water tank. Skeleton remains were brought by police personal with an alleged history that the remains belong to a child who has been missing since 2 years. The skeletal bones after anthropological study, forensic odontology findings and DNA profiling, were confirmed to be of the missing child's. A skeletonized body recovered from water is not capable of being identified by visual means, and hence, other examinations i.e., forensic odontology and DNA profiling, substantiate the case.

Towards the development of a biobased economy in Europe and India.

India has emerged as a key player with a high potential to develop a biomass and biobased economy due to its large geographic size and the massive amounts of agricultural and non agricultural biomass produced. India has joined hands with Europe to synchronize its efforts to create and facilitate the development of a biobased economy in this country. This paper aims to examine common research and development actions between the European Union (EU) and India to facilitate the development of these biobased economies. As a base, a thorough study has been performed considering the biomass potential and current status of the bioeconomy in both the EU and India based on the distillation of a series of 80 potential recommendations. The recommendations were grouped into four major categories: (1) biomass production, (2) by-products/waste, (3) biorefineries and (4) policy, market, and value-added products. A questionnaire was designed and distributed to key stakeholders belonging to: academia, industry, and policymakers in both India and the EU. A total of 231 responses were received and analyzed, based on the key recommendations made for the essential research and development topics that are of prime importance to develop biobased economies in both the EU and India. The findings of this study suggest recognizing the value-added contributions made by biobased products such as: food, feed, valuable materials and chemicals in both regions. It is important to reduce the overall process costs and minimize the environmental impacts of such a biobased economy.

Antifungal efficacy of herbs.

Candida carriage was reported to be common in oral cancer patients, with C. albicans being the predominant species. The prevalence of diseases caused by Candida species have been found to increase in recent years. AIM: The aim of our study was to find the antifungal activities at MIC of selected fifteen plant leaves extracts prepared in three different solutions (methanol and ethanol) against the opportunistic pathogen Candida albicans isolated from oral cavity infections. It may also help the clinician to treat the patient not only for the particular lesion that is present, but also to treat the infection by Candida albicans so as to reduce its potential to malignant transformation. Material n methods: Leaves extract of selected plant prepared in methanolic and eethanolic solution have been chosen for the investigation of in vitro antifungal activity which acts as expectorant and not having toxic properties on humans while for comparison or control, antifungal drugs have been taken. Results showed that Candida albicans shows most sensitivity towards the standard antibiotic cotrimoazol but very less towards other drugs like Fluconazole, minocycline, erythromycin respectively which indicated Candida albicans shows some resistance character towards drugs while the herbal extracts of Lawsonia inermis, Withania somnifer, Curcuma longa, Cymbopogon citrates and Zingiber officinale gives the best inhibitory effect and they have the potential to control growth of Candida albicans.

Integrating natural and engineered remediation strategies for water quality management within a low-impact development (LID) approach.

The objective of this paper is to demonstrate an interdisciplinary strategy combining both engineering- and biology-based approaches for stormwater and wastewater treatment. The work involves a novel and environmentally friendly surface material that can withstand urban load over its design service life, allows preliminary treatment through filtration, and diverts water to the subsurface to conduct secondary treatment below the surface through phytoremediation via the extensive rooting systems of trees. The present study highlights an interdisciplinary low-impact development (LID) approach developed for a polluted industrial wastewater site, for a cleaner and greener environment. The LID system involves (i) rhizofiltration and phytoremediation methods for removing heavy metals and organic pollutants using a hybrid poplar and aspen species; (ii) porous infrastructure produced using industrial waste, referred to as geopolymer pavers; and (iii) use of Silva cells as a tree-friendly and load support system. The design of the pavers over the Silva cells is innovative as it can deal with rainwater runoff and urban transportation loads simultaneously. The proposed system has the ability to extract heavy metals that are common in urban runoff or domestic and industrial effluents thus preserving the ecosystem naturally. The test site is only 15 m2, but designed for a water-retention capacity of 2 m3 (roughly 1:100 year design volume draining a 10 × 10 m parking lot), and remediation levels for Cu and Zn are expected to reach 180 mg/kg dry weight and 1200 mg/kg dry weight, respectively.