Background: Zinc deficiency is strongly correlated with prolonged diabetes mellitus and diabetic nephropathy (DN). Previously, glucose-lowering, insulinomimetic, and beta -cell proliferative activities of zinc oxide nanoparticles (ZON) have been reported. Considering these pleiotropic effects, we hypothesized that ZON modulates multiple cellular pathways associated with necroptosis, inflammation, and renal fibrosis, which are involved in progressive loss of renal function. Aim: This study evaluated the effect of ZON on renal function, leading to the alleviation of DN in streptozotocin (STZ)-induced type 1 diabetic Wistar rats and proposed a probable mechanism for its activity. Methods: Wistar rats ( n = 6/group) were used as healthy controls, diabetic controls, diabetic rats treated with ZON (1, 3, and 10 mg/kg), and insulin controls. Urine and serum biochemical parameters, glomerular filtration rate (GFR), and renal histology were also evaluated. Cultured E11 podocytes were evaluated in vitro for markers of oxidative stress, proteins associated with the loss of renal function, and genes associated with renal damage. Key findings: STZ-treated rats receiving oral doses of ZON showed enhanced renal function, with no histological alterations in the kidney tissue. ZON inhibited the TGF- beta /Samd3 pathway in renal fibrosis; blocked Ripk1/ Ripk3/Mlkl mediated necroptosis and protected against hyperglycemia-induced pyroptosis. In E11 podocytes, ZON reduced oxidative stress under high glucose conditions and retained podocyte-specific proteins. Significance: A probable mechanism by which ZON prevents DN has been proposed, suggesting its use as a complementary therapeutic agent for the treatment of diabetic complications. To the best of our knowledge, this is the first study to demonstrate the in vitro effects of ZON in cultured podocytes.

Copper and other copper-containing compounds can be produced as nanoparticles by "green nanotechnologies." The most striking features of nanoparticles, such as their facile synthesis, easy synthesis process scalability, and abundance of raw materials (including precursors), have prompted their exploration in various agricultural applications. Particularly, preliminary data on their use as fungicidal agents and plant growth-promoting agents are now available. With these developments, it is expected that copper-based nanofungicides will emerge as "next-generation agrochemicals." A minimal impact on the environment during the production of nanomaterials will ensure their sustainable applications in the agricultural sector. Copper nanofungicidal formulations have many advantages. Besides providing the necessary antifungal activity, the nanofungicides, with their inherently low concentrations of copper, can benefit plant growth, resulting in increased yields. Furthermore, the associated ecotoxicological risks of nanofungicides are negligible. With the new advances, better and "smarter" nanoformulations tailored to release the active ingredient on demand can be made. These advanced nanofungicidal materials can go a long way towards preventing ecotoxicity in the environment and making agriculture much safer, which is very important.

The emergence of drug resistance in cancer cells is among the major challenges for treating cancer. In the last few years, the co-delivery of drug and siRNA has shown promising results against drug-resistant cancers. In the present study, we developed mesoporous silica-based multifunctional nanocarrier for co-delivery against drug-resistant triple-negative breast cancer (TNBC) cells. We synthesized the nanocarrier by modifying mesoporous silica nanoparticles with poly-L-arginine, polyethylene glycol and AS1411 aptamer to impart siRNA binding ability, biocompatibility, and cancer cell specificity, respectively. We optimized the loading of doxorubicin (DOX) within the developed nanocarrier to avoid interference with siRNA binding. We ascertained the target specificity by performing a receptor blockade assay during cellular uptake studies. The cytotoxic efficacy of DOX and siRNA co-delivered using the developed nanocarrier was assessed using DOX-resistant MDA-MB-231 TNBC cells. The nanocarrier exhibited >10-fold and 40-fold reduction in the IC50 values of DOX due to co-delivery with BCl-xL and BCL-2 siRNA, respectively. The results were further validated using a 3-D in vitro cell culture system. This study demonstrates that the targeted co-delivery of drug and siRNA has a strong potential to overcome drug resistance in TNBC cells.

Background The adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART. Results TNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs. Conclusions We show that the combination of TNF and AuNPs exhibits multifunctional activity, viz . anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS. Graphical Abstract

The setback in the practical clinical use of RNA interference (RNAi)-based cancer treatment stems from the lack of targeted small interfering RNA (siRNA) delivery. Here, we show that luteinizing hormone-releasing hormone(LHRH) analog-tethered multi-layered polyamidoamine (PAMAM) nanoconstructs silence the anti-apoptotic MCL-1 gene in LHRH receptor overexpressing human breast (MCF-7) and prostate cancer (LNCaP) cells with 70.91 % and 74.10 % efficiency, respectively. These results were confirmed by RT-PCR. The Acridine orange/Ethidium bromide (AO/EB) dual staining revealed that the silencing of MCL-1 induced apoptosis in both the cell lines. In vivo tumor regression studies performed using MCF-7 and LNCaP xenografted severe combined immunodeficiency(SCID) mice demonstrated highly improved tumor regression in groups treated with targeted nanoconstructs complexed with MCL-1 siRNA (T + siMCL-1) compared to the other treatment groups. The quantitative RT-PCR results of tumor tissues demonstrated significant MCL-1 gene silencing, i.e., 73.76 % and 92.63 % in breast and prostate tumors, respectively, after T + siMCL-1 treatment. Reduction in MCL-1 protein expression as assessed by immunohistochemistry further confirmed these results. Furthermore, the caspase 3/7 assay demonstrated apoptosis in the MCL-1 silenced tissues. The study strongly suggests that targeted delivery of siRNAs using multi-layered dendrimer nanostructures could be an effective therapy for LHRH overexpressing cancers.

Shrimp farming is an important socioeconomic activity worldwide. Infectious myonecrosis virus (IMNV) is an important shrimp virus responsible for significant mortality (up to 70

Five novel permanent cell lines have been established from gill, heart, kidney, eye and fin of snubnose pompano, Trachinotus blochii. They were designated as snubnose pompano gill (SPG), snubnose pompano heart (SPH), snubnose pompano kidney (SPK), snubnose pompano eye (SPE) and snubnose pompano fin (SPF), respectively. All these cell lines were characterized and cryopreserved successfully at different passage levels. Cell lines were passaged every alternate day; SPG, SPH, SPK, SPE and SPF cell lines attained passage levels of 68, 74, 82, 79 and 106, respectively, since the initiation of their development in 2019. The cell lines grew well in Leibovitz's 15 medium containing 15% foetal bovine serum at 28°C. Immunophenotyping of the cell lines revealed the presence of fibronectin and pancytokeratin. No mycoplasma contamination was found. The transfection study revealed the gene expression efficiency of these cell lines by expressing the green fluorescent protein (GFP). The authentication on origin of cell lines from T. blochii was confirmed by amplification of species-specific mitochondrial cytochrome oxidase I gene. The results showed the susceptibility of these cell lines to fish nodavirus (FNV) and tilapia lake virus (TiLV) and resistance to cyprinid herpesvirus 2 (CyHV-2). The FNV infection in the cell lines was confirmed by RT-PCR, Western blot, ELISA and immunocytochemistry, while TiLV infection was confirmed by RT-PCR assay. These results revealed that these cell lines are suitable for virological and foreign gene expression studies.

Heavy reliance on agriculture will continue for meeting the needs of the ever growing population all over the world. Variety of plant pathogens affect yield and quality of agricultural produce adversely which leads to huge economic losses. To this end, conventional diagnostics techniques were supplemented by developments in serological and molecular methods; but with the advent of nanotechnology, possibilities for detection of ultra-trace amounts of analytes exist due to the unprecedented characteristics of materials in their 'nano' forms. In agri-bio-nanotechnology, existing technologies are being coupled with advanced nanomaterials and nanocomposites for the detection of DNA, RNA, proteins, etc. to achieve attributes of an 'ideal' phytodiagnostic such as sensitivity, specificity, reproducibility, affordability, and portability. Specifically, with the use of nanotechnology-based sensors and P-O-C devices, early disease warnings can be obtained, and applications of pesticides, insecticides, antimicrobials could be planned, resulting in reduce the economic losses and ensuring 'safety' and 'security'. The present chapter is a review on all efforts at development of nanophytodiagnostics for on-farm applications.

[This corrects the article DOI: 10.2147/IJN.S104617.].

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

Pathogens and pests pose a constant threat to crop production activities. Newer technologies, viz., "nanotechnology" are required to achieve higher crop production while maintaining optimal fertilizer and water use efficiency. Due to their chemical nature, copper and copper oxide nanoparticles have emerged as unique broad-spectrum antimicrobial and antifungal agents against phytopathogens. The attributes such as ease of synthesis, availability of low-cost precursors, scalable manufacture, etc., have engaged researchers to explore their use in field-scale experiments as well as in the form of antimicrobial packaging to extend the shelf life of food. Furthermore, the use of such materials may reduce the negative environmental consequences. All such studies are reviewed here. Detailed studies on the environmental effects of these materials need to be conducted to address public concerns on the use of copper-based nanostructures.

Macrobrachium rosenbergii nodavirus (MrNV) affects the larval, post-larval, and juvenile stages of M. rosenbergii, the giant freshwater prawn, causing white tail disease (WTD). With its high mortality, WTD is a severe threat to shrimp and prawn farming. We describe the development and optimization of an antibody-based lateral flow assay (LFA) for the early detection of MrNV in the post-larval (PL) stage of M. rosenbergii. The LFA parameters (viz., the detergent concentration, GNPs-antibody conjugate, antibody concentration applied to the test line and membrane porosity) were optimized using the design of experiment (L9 orthogonal array). Under optimized conditions, MrNV could be detected within 20 min with high specificity, reproducibility, and sensitivity (LOD = 104 particles/ng of total RNA). In virus challenge experiments, MrNV could be detected on the seventh day of infection in the PL stage. LFA was validated using infected PL samples collected from the field (hatcheries and nurseries) (n = 80) in conjunction with ‘gold standard’ qRT-PCR test. High sensitivity (100%) and specificity (90%) of LFA, with a Cohen's kappa coefficient of 0.936, suggested ‘good agreement’ between the developed LFA and qRT-PCR. The developed LFA has an immense potential of averting losses by rapid detection of MrNV at PL stage in M. rosenbergii.

Zinc (Zn) nanostructures in the form of particles, rods, springs, flowers, belts, etc. are used in numerous applications, including supercapacitors, paints, sensor materials, antimicrobial materials, and others. In its nano-form, zinc oxide (ZnO) in particular is being evaluated as a micronutrient fertilizer in agriculture. Several studies document the positive effects of nanoscale ZnO on seed germination, plant growth, and yield of crop plants, leafy vegetables, and pulses. Also, results on crop biofortification, modulation of soil activity, and alleviation of abiotic stress are indeed promising. This chapter is a review of these studies and the need for detailed studies on the fate and transportation of Zn nanostructures in the ecosystem is highlighted. Food security is of paramount importance in the coming years, with nanotechnology interventions in agriculture potentially having far-reaching effects.

ABSTRACT:Myocardial infarction is a substantial contributor to ischemic heart diseases, affecting a large number of people leading to fatal conditions worldwide. MicroRNAs (miRNAs) are explicitly emerging as excellent modulators of pathways involved in maintaining cardiomyocyte survival, repair, and regeneration. Altered expression of genes in cardiomyocytes postinfarction can lead to the disordered state of the myocardium, such as cardiac hypertrophy, ischemia-reperfusion injury, left ventricular remodeling, and cardiac fibrosis. Therapeutic targeting of miRNAs in cardiomyocytes can potentially reverse the adverse effects in the heart postinfarction. This review aims to understand the role of several miRNAs involved in the regeneration and repair of cardiomyocytes postmyocardial infarction and presents comprehensive information on the subject.

Aim: Myocardial infarction is a tissue injury that leads to apoptosis of cardiomyocytes. This can be prevented by using miRNAs, but its delivery to cardiomyocytes is a major hurdle. We aimed to deliver miRNAs using poly(amidoamine)-histidine (PAMAM-His) nanocarriers to prevent apoptosis. Materials & methods: The PAMAM-His nanoparticles were synthesized and assessed for their transfection efficiency of miRNAs to prevent apoptosis in hypoxia/reperfusion-induced H9c2 as well as primary cultured cardiomyocytes. Results & conclusion: miRNAs-nanoparticle complexes exerted a significant antiapoptotic effect on the H9c2 and primary rat ventricular cardiomyocytes. Enhanced expression of antiapoptotic genes and decreased expression of proapoptotic genes were observed. PAMAM-His nanoparticles effectively delivered miRNAs to the cardiomyocytes and prevented the hypoxia/reperfusion-induced apoptosis critical in myocardial infarctions.

Bacteria, fungi, viruses, and nematodes are the major causal agents of plant diseases. These phytopathogens are responsible for about 10–40% losses in productivity and quality of food crops and horticultural produce. Although eradication of pathogens is not possible, control of plant diseases has been an area of continuous improvement/research. Use of antimicrobials, bacteriophages, and biocontrol agents, natural and synthetic agrochemicals along with best farm management practices constitute integrated measures for disease control. However, the quest for new materials continues due to pesticide resistance in the pathogens, emergence of new serotypes, and accumulation of high quantities of agrochemical contaminants in the ecosystem and associated environmental hazards, specificity of biocontrol agents, succession of pathogens during the plant growth phase, etc. The emergence of “nanotechnology,” a multidisciplinary field of research, has provided a plethora of nanomaterials for potential applications in the agricultural sector. Control of plant diseases requires agents that reduce the pathogen to manageable levels, tools for early-stage detection of pathogen, and compounds that elicit immune response in the host plants. Nanomaterials have in fact been assessed for their utility in all these approaches for disease control. The present review discusses nanomaterials for controlling phytopathogens, nanomaterials in plant disease diagnostics, and nanomaterials as elicitors of the plant immune system. These nanomaterials thus represent new weapons in the fight against the phytopathogens. Recent studies indicate that nanomaterials will be a crucial component in the agroecosystem.

The objectives of this study were to reduce the cytotoxic effect of nevirapine (NVP) and to enhance its anti-HIV efficacy through mesoporous silica nanoparticles (MSNPs) mediated delivery. MSNPs were synthesized and characterized by various techniques. Confocal microscopy and flow cytometry results exhibited efficient uptake of FITC-conjugated MSNPs in TZM-bl cells. The NVP was loaded within MSNPs, and its anti-HIV1 efficacy was assessed on HIV1 (R5 and X4 variants) infected TZM-bl cells and further confirmed on peripheral blood mononuclear cells (PBMCs). The in vitro assessment of the anti-HIV1 potential of NVP and NVP-MSNPs in HIV1 infected TZM-bl cells and PBMCs showed increased efficacy of NVP upon loading within MSNPs with significant increase in therapeutic index. The increased efficacy against HIV1 was accompanied by reduced cytotoxicity to TZM-bl cells and PBMCs. Further, reverse transcriptase (RT) assay confirmed the inhibitory effect on RTase, which is a key enzyme in HIV-1 replication. The present study showed that entrapment of NVP within MSNPs led to an increased efficacy with reduced cytotoxic effect resulting in the enhanced therapeutic index (TI).

Iron (Fe), zinc (Zn), and selenium (Se) are essential micronutrients for both plants and humans. Micronutrients from soil move to the plants and finally reach the animals, and humans. Intensive agriculture has led to a decrease in soil quality, and two-third of the soils across the world are micronutrient deficient. Crops cultivated on such soils make them severely micronutrient deficient, causing "micronutrient malnutrition" in humans. Nutritional quality of grains is an essential aspect of food security as micronutrient-imbalanced diet can lead to a variety of non-communicable disorders and decrease the overall immune status. Micronutrient-enriched cereals can provide the "more" and not just the protein and calories, thus providing a sustainable solution to the problem of "hidden hunger." Research on genetic biofortification and introduction of "transgenic crops" with better micronutrient uptake characteristic has to be complemented by agronomic biofortification for "quick" enrichment of micronutrients. Studies on a global scale prove the utility of agronomic biofortification of cereals, millets, and pulses to overcome Fe, Zn, and Se deficiencies. Research on the use of conventional as well as newer nanotechnology-based soil- as well as foliar-applied fertilizers is on the forefront. Ensuring maximum "nutrient-use efficiency" while causing minimal harmful/damaging effects on the environment is the need of the hour. Efforts at the restoration of soil quality and managing the biotic components also lead to positive biofortification outcomes. Moreover, understanding of the mobilization of the soil and/or foliar-applied micronutrient can help in identifying molecular targets for genetic biofortification. Upon establishing bioavailability of the enriched nutrient, the participation of farmers and policy-makers for successful implementation of the technologies developed in laboratories is exceptionally crucial.