An insight into impact of nanomaterials toxicity on human health.

In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms. This altered nature can be attributed to their unique physicochemical profile. They can adversely affect human health and the environment. Nanomaterials that have been released into the environment tend to accumulate over time and can cause a significant impact on the ecosystem and organisms with adverse health effects. Increased use of nanoparticles has led to increased human exposure in their daily lives, making them more vulnerable to nanoparticle toxicity. Because of their small size, nanomaterials can readily cross biological membranes and enter cells, tissues, and organs. Therefore, the effect of nanomaterials on the human environment is of particular concern. The toxicological effects of nanomaterials and their mechanisms of action are being researched worldwide. Technological advances also support monitoring new nanomaterials marketed for industrial and household purposes. It is a challenging area because of the exceptional physicochemical properties of nanomaterials. This updated review focuses on the diverse toxicological perspective of nanomaterials. We have discussed the use of different types of nanoparticles and their physiochemical properties responsible for toxicity, routes of exposure, bio-distribution, and mechanism of toxicity. The review also includes various in vivo and in vitro methods of assessing the toxicity of nanomaterials. Finally, this review will provide a detailed insight into nano material-induced toxicological response, which can be beneficial in designing safe and effective nanoparticles.

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approach is biomaterial-assisted biotherapy, which takes advantage of biomaterials' special capabilities, such as high biocompatibility and bioactive characteristics. When administered via different routes, drug molecules deal with biological barriers; DDSs help them overcome these hurdles. With their adaptable features and ample packing capacity, biomaterial-based delivery systems allow for the targeted, localised, and prolonged release of medications. Additionally, they are being investigated more and more for the purpose of controlling the interface between the host tissue and implanted biomedical materials. This review discusses innovative nanoparticle designs for precision and non-personalised applications to improve precision therapies. We prioritised nanoparticle design trends that address heterogeneous delivery barriers, because we believe intelligent nanoparticle design can improve patient outcomes by enabling precision designs and improving general delivery efficacy. We additionally reviewed the most recent literature on biomaterials used in biotherapy and vaccine development, covering drug delivery, stem cell therapy, gene therapy, and other similar fields; we have also addressed the difficulties and future potential of biomaterial-assisted biotherapies.

Comprehensive characterization of protease inhibiting gene family, cis-regulatory elements, and protein interaction network in linseed and their expression upon bud fly infestation.

Linseed, also known as flax is an important oilseed crop with many potential uses in paint, textile, food and pharmaceutical industries. Susceptibility to bud fly (Dasyneura lini Barnes) infestation is a serious biotic concern leading to severe yield penalty in linseed. Protease inhibitors (PIs) are potential candidates that activate during the insect-pest attack and modulate the resistance. In the present study, we explored the PI candidates in the linseed genome and a total of 100 LuPI genes were identified and grouped into five distinct subgroups. The analysis of cis-acting elements revealed that almost all LuPI promoters contain several regulatory elementary related to growth and development, hormonal regulation and stress responses. Across the subfamilies of PIs, the specific domains are consistently found conserved in all protein sequences. The tissue-specific in-silico expression pattern via RNA-seq revealed that all the genes were regulated during different stress. The expression through qRT-PCR of 15 genes revealed the significant up-regulation of LuPI-24, LuPI-40, LuPI-49, LuPI-53, and LuPI-63 upon bud fly infestation in resistant genotype EC0099001 and resistant check variety Neela. This study establishes a foundation resource for comprehending the structural, functional, and evolutionary dimensions of protease inhibitors in linseed.

Antitubercular evaluation of dihydropyridine-triazole conjugates: design, synthesis, in vitro screening, SAR and in silico ADME predictions.

This study investigates the potential of click chemistry for the development of novel anti-tuberculosis agents. A targeted library of 1,4-dihydropyridine-1,2,3-triazole conjugates was synthesized and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Ra using the resazurin microtiter assay (REMA). Among the synthesized derivatives, compounds J10, J11, J14, J22 and J23 demonstrated significant antimycobacterial activity. These compounds exhibited low MIC values ranging from 6.24 to 6.64 µg mL-1, highlighting their promising potential as lead compounds for further developing novel tuberculosis therapeutics. In addition to the promising in vitro activity, structure-activity relationship (SAR) analysis revealed that electron-withdrawing groups on the aryl-substituted ring of the dihydropyridines (J10-J24), a triazole with an unsubstituted aryl ring or with electron-donating groups (methyl or methoxy), and a geminal dimethyl group are essential structural features for the observed antitubercular activity. Furthermore, in silico ADME (absorption, distribution, metabolism, and excretion) parameters and pharmacokinetic studies supported the potential of these conjugates for oral bioavailability. These findings collectively highlight the 1,4-dihydropyridine-1,2,3-triazole scaffold as a promising platform for developing novel orally active anti-tuberculosis drugs.

Effect of psychoeducation in late life depression: A randomized controlled trial.

Background: Depression is one of the leading causes of disability worldwide, and after the global pandemic COVID-19, it has become even more worse. The treatment of depression should involve pharmacological treatment along with the various kinds of psychotherapies (non-pharmacological management). This study aims to determine the result of psychoeducation in late-life depression by using Hamilton Depression Rating Scale 17 items (HAMD) and Geriatric Depression Scale (Hindi version) (GDS-H). Material and Methods: The study was registered on the Control Trial Registry of India (CTRI) via CTRI/2019/05/018956. It is a prospective randomized controlled trial of 4 weeks, where 154 patients aged more than 60 years were randomized into two groups, case group (A) (n = 83) who received psychoeducation along with treatment as usual, whereas control group (B) (n = 71) who received placebo along with treatment as usual. The patients were assessed using Hamilton Depression Rating Scale 17 items (HAMD), Geriatric Depression Scale (Hindi version) (GDS-H) on baseline visit (Day 0), on first follow-up (Day 14), and second follow-up (Day 28). Hindi Mental Status Examination (HMSE) was used on the baseline visit to rule out primary cognitive impairment. Results: The results were analyzed, and it was concluded that both the groups have significant decrease in HAMD-17 and GDS-30 scores over a period of time with a P-value of <0.001 in both.

Early bladder dysfunction after vesicovaginal fistula repair: A prospective comparative analysis of transvaginal, open, and laparoscopic abdominal approaches.

INTRODUCTION: We aim to compare the clinical and urodynamic profile of lower urinary tract symptoms (LUTS) in patients undergoing laparoscopic, open transabdominal, and laparoscopic transabdominal vesicovaginal fistulae (VVF) repair at 3 months of repair, that is, in early postoperative period. MATERIALS AND METHODS: Fifty-one consecutive patients with endoscopically confirmed VVF were enrolled in our study over 2 years. Malignant fistulae, radiation-induced, and complex fistulae were excluded after cross-sectional imaging. All patients underwent a postoperative assessment for the success of the repair. Then at 3 months, they completed the American Urological Association Symptom Score questionnaire and underwent a dual channel pressure-flow urodynamic study. The results of transvaginal, laparoscopic, and open transabdominal repairs were compared. RESULTS: All patients belonged to the Indian Caucasian race. The mean age was 35.43 ± 6.63 years. Thirty-two patients had supratrigonal and 19 had trigonal fistulae. Laparoscopic transabdominal repair was done in 15 patients, open transabdominal repair in 22 patients, and transvaginal repair in 14 patients. Forty-six patients reported some LUTS at a median follow-up of 5.83 ± 2.37 months postoperatively. Only 18 (35.2%) of these patients had moderate to severe symptoms The postoperative bladder dysfunction rates in open transabdominal, transvaginal and laparoscopic transabdominal groups were 36.4%, 28.6%, and 20%, respectively. Twenty-seven patients (52.9%) had some urodynamic abnormality, that is, small capacity (5), high voiding pressures (14), genuine stress incontinence (3), and poor compliance (3). Bladder capacity was a significant predictor of bladder dysfunction in our patients. CONCLUSIONS: In our study, all three surgical approaches were associated with bladder dysfunction, however, it was the least in the laparoscopic transabdominal approach. Postoperative bladder capacity is a significant predictor of bladder dysfunction.

Quality by design-based development and in vitro evaluation of dual release tablet of etoricoxib and thiocolchicoside: A novel chronotherapeutic approach for arthritis pain management.

OBJECTIVE: The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside. MATERIAL AND METHOD: The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets. RESULT: Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm2. Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution. CONCLUSION: A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

Nano-Formulation Approaches to Enhance Transdermal Drug Delivery-An Updated Review of Nanovesicular Carrier "Transethosomes".

Transdermal drug delivery is an attractive and patient-friendly route for administering therapeutic agents. However, the skin's natural barrier, the stratum corneum, restricts the passage of many drugs, limiting their effectiveness. To overcome this challenge, researchers have developed various nanocarriers to enhance drug penetration through the skin. Transethosomes, a novel and promising drug delivery system, have emerged as an innovative solution for improving transdermal drug delivery. Transethosomes are a hybrid of two established nanocarriers: ethosomes and transfersomes. Ethosomes are lipid-based vesicles that can accommodate lipophilic and hydrophilic drugs, while transfersomes are deformable lipid vesicles designed to enhance skin penetration. Transethosomes combine the advantages of both systems, making them ideal candidates for efficient transdermal drug delivery. They are composed of phospholipids, ethanol, and water and exhibit high flexibility, enabling them to squeeze through the tight junctions of the stratum corneum. This abstract reviews the key characteristics of transethosomes, including their composition, preparation methods, mechanisms of action, characterization parameters, and prospects. Moreover, the recent advancements and applications of transethosomes in delivering various therapeutic agents, such as analgesics, anti-inflammatories, hormones, and skincare products, are explored. The enhanced skin penetration capabilities of transethosomes can potentially reduce systemic side effects and improve patient compliance, making them a valuable tool in the field of transdermal drug delivery. In conclusion, transethosomes represent a promising platform for overcoming the challenges of transdermal drug delivery. Their unique properties enable efficient drug permeation through the skin, offering a more controlled and effective means of administering a wide range of pharmaceutical and cosmetic products. This abstract highlights the potential of transethosomes as a valuable addition to the field of transdermal drug delivery and paves the way for further research and development in this area.

Unveiling the potential of polymer cholesteric liquid crystal interpenetrating networks as a label-free alcohol biochemical sensor.

In this study, an optical sensor is developed, incorporating hydrogen-bonded photonic array dots containing poly(acrylic acid) (PAA) within a polymer cholesteric liquid crystal interpenetrating polymer network (PCLCIPN) framework, thereby effectively controlling porosity. This methodology involves the fabrication of a porous photonic film, subsequent infusion with a hydrogel (PAA), and precise UV-curing to generate patterned array dots. The sensor exhibits exceptional discriminatory capability between methanol and ethanol, accurately discerning their varying concentrations within alcohol solutions. The optical sensing performance of the film is rigorously evaluated through continuous monitoring of wavelength shifts in the transmission spectrum across various alcohol concentrations. Notably, the observed wavelength shifts demonstrate a linear correlation with the concentration of alcohol, thereby enabling precise quantitative analysis of the alcohol solutions. The sensor exhibits a sensitivity of 0.44 nm/% for ethanol concentrations ranging from 5% to 60%, increasing to 2.1 nm/% for concentrations between 60% and 80%. Similarly, for methanol, sensitivities of 0.68 nm/% (5-60%) and 2.2 nm/% (60-80%) are recorded. Remarkably, this sensitivity trend extends seamlessly to 1 : 1 ethanol/methanol ratios, with values of 0.49 nm/% (5-60%) and 2.25 nm/% (60-80%). Furthermore, these sensors demonstrate colorimetric response to different alcohols, rendering them accessible and cost-effective biosensors for visual detection, thus obviating the necessity for complex analytical instruments.

Phyto-Fabrication of Moringa Oleifera Peel-Sourced Silver Nanoparticles: A Promising Approach for Combating Hepatic Cancer by Targeting Proinflammatory Cytokines and Mitigating Cytokine Storms.

Hepatocellular carcinoma (HCC) arises from precancerous nodules, leading to liver damage and inflammation, which triggers the release of proinflammatory cytokines. Dysregulation of these cytokines can escalate into a cytokine storm, causing severe organ damage. Interestingly, Moringa oleifera (M. oleifera) fruit peel, previously discarded as waste, contains an abundance of essential biomolecules and high nutritional value. This study focuses on the eco-friendly synthesis of silver nanoparticles infused with M. oleifera peel extract biomolecules and their impact on regulating proinflammatory cytokines, as well as their potential anticancer effects against Wistar rats. The freshly synthesized nanoformulation underwent comprehensive characterization, followed by antihepatic cancer evaluation using a diethyl nitrosamine-induced model (at a dose of 200 mg kg-1 BW). The study demonstrates a significant reduction in proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, and nuclear factor kappa beta (NF-κB). Furthermore, it confirms that the newly biosynthesized silver nanoparticles exhibit additional potential against hepatic cancer due to their capped biomolecules.