Guardians of the Gut: Harnessing the Power of Probiotic Microbiota and Their Exopolysaccharides to Mitigate Heavy Metal Toxicity in Human for Better Health.

Heavy metal pollution is a significant global health concern, posing risks to both the environment and human health. Exposure to heavy metals happens through various channels like contaminated water, food, air, and workplaces, resulting in severe health implications. Heavy metals also disrupt the gut's microbial balance, leading to dysbiosis characterized by a decrease in beneficial microorganisms and proliferation in harmful ones, ultimately exacerbating health problems. Probiotic microorganisms have demonstrated their ability to adsorb and sequester heavy metals, while their exopolysaccharides (EPS) exhibit chelating properties, aiding in mitigating heavy metal toxicity. These beneficial microorganisms aid in restoring gut integrity through processes like biosorption, bioaccumulation, and biotransformation of heavy metals. Incorporating probiotic strains with high affinity for heavy metals into functional foods and supplements presents a practical approach to mitigating heavy metal toxicity while enhancing gut health. Utilizing probiotic microbiota and their exopolysaccharides to address heavy metal toxicity offers a novel method for improving human health through modulation of the gut microbiome. By combining probiotics and exopolysaccharides, a distinctive strategy emerges for mitigating heavy metal toxicity, highlighting promising avenues for therapeutic interventions and health improvements. Further exploration in this domain could lead to groundbreaking therapies and preventive measures, underscoring probiotic microbiota and exopolysaccharides as natural and environmentally friendly solutions to heavy metal toxicity. This, in turn, could enhance public health by safeguarding the gut from environmental contaminants.

Leishmania major MAPK4 intercepts and redirects CD40 signaling promoting infection.

The parasite Leishmania resides as amastigotes within the macrophage parasitophorous vacuoles inflicting the disease Leishmaniasis. Leishmania selectively modulates mitogen-activated protein kinase (MAPK) phosphorylation subverting CD40-triggered anti-leishmanial functions of macrophages. The mechanism of any pathogen-derived molecule induced host MAPK modulation remains poorly understood. Herein, we show that of the fifteen MAPKs, LmjMAPK4 expression is higher in virulent L. major. LmjMAPK4- detected in parasitophorous vacuoles and cytoplasm- binds MEK-1/2, but not MKK-3/6. Lentivirally-overexpressed LmjMAPK4 augments CD40-activated MEK-1/2-ERK-1/2-MKP-1, but inhibits MKK3/6-p38MAPK-MKP-3, phosphorylation. A rationally-identified LmjMAPK4 inhibitor reinstates CD40-activated host-protective anti-leishmanial functions in L. major-infected susceptible BALB/c mice. These results identify LmjMAPK4 as a MAPK modulator at the host-pathogen interface and establish a pathogen-intercepted host receptor signaling as a scientific rationale for identifying drug targets.

CCSfind: A tool for chemically informed LC-IM-MS database building.

In addition to providing critical knowledge of the accurate mass of ions, ion mobility-mass spectrometry (IM-MS) delivers complementary data relating to the conformation and size of ions in the form of an ion mobility spectrum and derived parameters, namely, the ion's mobility (K) and the IM-derived collision cross section (CCS). However, the maximum amount of information obtained in IM-MS measurements is not currently transferred into analytical databases including the full mobility spectra (CCS distributions) as well as capturing of additional ion species (e.g., adducts) into the same compound entry. We introduce CCSfind, a new tool for building comprehensive databases from experimental IM-MS measurements of small molecules. CCSfind allows predicted ion species to be chosen for input chemical formulae, which are then targeted by CCSfind after parsing open source mzML input files to provide a unified set of results within a single data processing step. CCSfind can handle both chromatographically separated isomers and IM separation of isomeric ions (e.g., "protomers" or conformers of the same ion species) with simple user control over the output for new database entries in SQL format. Files of up to 1 GB can be processed in less than 2 min on a desktop computer with 32 GB RAM with computational time scaling linearly with the size of the input mzML file or the number of input molecular formulae. Results are manually reviewed, annotated with experimental settings, before committing the database where the full dataset can be retrieved.

Ru-Catalyzed and Selenium-Directed Selective Formation of ortho- and Dialkenylated Selanes, Mixed Organoselenoethers, and Isoselenochromenes.

Herein, the Ru-catalyzed chemo- and regioselective formation of four novel organoselenium compounds is established. Mono- and dialkenylated selanes were formed by the Se-directed o-C-H activation of benzyl(phenyl)selanes with alkynes. Unprecedented debenzylative/dearylative hydroselenations of alkynes were performed by slightly varying the amount of catalyst and temperature. Catalyst-driven direct formation of novel isoselenochromenes is also recorded. Altogether, 45 new organoseleno compounds were synthesized in good amounts with varieties of alkynes and selanes. This is the first report of its kind to deal with the synthesis of novel, challenging, and unusual organoseleno compounds in one reaction.

Selenated NHC-Pd(II) Pincer Complex Catalyzed, Temperature-Dependent Selective Hydroamination and Oxidative Amination of Olefins: Formation of Enamine Esters and ß-Amino Esters under Solvent-Free and Aerobic Conditions.

NHC-Pd(II) pincer catalyzed oxidative amination and hydroamination of olefins is developed under solvent-free aerobic conditions. Reaction offered a temperature-controlled synthesis of (Z)-enamine and ß-amino esters to provide easy access and remarkable functional group tolerance for a variety of enamines. The developed approach renders an opportunity of scalability and flexibility, and besides this, the produced enamines can be transformed into many N-containing heterocycles, underscoring its potential usage in synthetic and pharmaceutical chemistry. Moreover, it is the first report for coupling of aniline with styrene.

Secondary metabolite induced tolerance to Fusarium oxysporum f.sp. cubense TR4 in banana cv. Grand Naine through in vitro bio-immunization: a prospective research translation from induction to field tolerance.

An innovative tissue culture mediated incorporation of metabolite-based biomolecule (Bio-immune) at in vitro stage itself in banana cv. Grand Naine was developed and validated for the production of Fusarium oxysporum f.sp. cubense TR4 tolerant plantlets. The novel bio-immune formulation developed by us, exhibited a significant antifungal potency against Foc TR4 with a high percent inhibition (100%) at a 2.5% concentration of bio-immune on the 5th, 7th, and 9th DAI. Bio-immune integrated during in vitro shoot proliferation stage in banana cv. Grand Naine recorded significant enhancement in the growth of roots and shoots. Bio-immune (0.5%) fortified media produced 12.67 shoots per clump whereas control registered only 9.67 shoots per clump. Similarly, maximum root numbers (7.67) were observed in bio-immune plants which were significantly higher over control (5.0). The bio-immunized banana transplants recorded a higher survival rate (97.57%) during acclimatization as compared to the control (94.53%). Furthermore, evaluation of the bio-immunized plants in pot experiments revealed that unimmunized plants treated with FocTR4 (TF) exhibited mortality between 60 and 90 days. On the 90th day after planting, a high mean disease severity index (DSI) of 3.45 was observed with unimmunized plantlets while the bio-immunized plants (TFBI) and ICAR-FUSICONT treated plants (TFTR) showed substantially reduced DSI (0.20 and 1.00) compared to FocTR4 treated control (TF). Significant increases in polyphenol oxidase (PPO), peroxidase (POD), ß-1,3-glucanase, phenylalanine ammonia-lyase (PAL), chitinase activities, and enhanced phenol contents were recorded in bio-immunized plants compared to unimmunized plants. Field experiments at two different locations in Bihar, India revealed that bunch weight, no. of hands/bunch, and no. of fingers/hand of bio-immune treated plants were significantly higher compared to the control.

Anti-citrullinated histone monoclonal antibody CIT-013, a dual action therapeutic for neutrophil extracellular trap-associated autoimmune diseases.

Neutrophil extracellular traps (NETs) contribute to the pathophysiology of multiple inflammatory and autoimmune diseases. Targeting the NETosis pathway has demonstrated significant therapeutic potency in various disease models. Here, we describe a first-in-class monoclonal antibody (CIT-013) with high affinity for citrullinated histones H2A and H4, which inhibits NETosis and reduces tissue NET burden in vivo with significant anti-inflammatory consequences. We provide a detailed understanding of the epitope selectivity of CIT-013. Detection of CIT-013 epitopes in rheumatoid arthritis (RA) synovium provides evidence that RA is an autoimmune disease with excessive citrullinated NETs that can be targeted by CIT-013. We show that CIT-013 acts upon the final stage of NETosis, binding to its chromatin epitopes when plasma membrane integrity is compromised to prevent NET release. Bivalency of CIT-013 is necessary for NETosis inhibition. In addition, we show that CIT-013 binding to NETs and netting neutrophils enhance their phagocytosis by macrophages in an Fc-dependent manner. This is confirmed using a murine neutrophilic airway inflammation model where a mouse variant of CIT-013 reduced tissue NET burden with significant anti-inflammatory consequences. CIT-013's therapeutic activity provides new insights for the development of NET antagonists and indicates the importance of a new emerging therapy for NET-driven diseases with unmet therapeutic needs.

Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry.

Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and herpes simplex virus type-1 (HSV-1) using different mechanisms. Interestingly, in the case of SARS-CoV-2, the pre-treatment of target cells with pAuNPsQ inhibited the viral entry, but the pre-treatment of the virus with pAuNPsQ did not affect viral entry into the host cell. In contrast, pAuNPsQ demonstrated effective blocking capabilities against HSV-1 entry, either during the pre-treatment of target cells or by inducing virus neutralization. In addition, pAuNPsQ also significantly affected HSV-1 replication, evidenced by the plaque-counting assay. In this study, we also tested the chemically synthesized gold nanoparticles (cAuNPs) of identical size and shape and observed comparable effects. The versatility of plant cell-based nanomaterial fabrication and its modification with bioactive compounds opens a new frontier in therapeutics, specifically in designing novel antiviral formulations.

Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.

Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2-Skp2-p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression. SIGNIFICANCE: The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression. See related commentary by Mishra et al., p. 4008.

Post-mortem interval estimation using miRNAs of road traffic accident cases: A forensic molecular approach.

In forensic examination accurate estimation of post-mortem interval (PMI) is a challenging task, particularly in the advanced stages of decomposition. The existing methods (algor mortis, livor mortis, rigor mortis, putrefaction etc) used for estimating PMI rely on analyzing the physical, biochemical, and metabolic changes that occur in the corpse after death. While these methods have shown some level of effectiveness in estimating PMI during the early stages of decomposition, accurate estimation becomes increasingly challenging during the later stages of putrefaction when the body undergoes significant changes. Recently, microRNA (miRNA) profiling due to its relatively small size and stability has emerged as a promising tool in several areas of forensics. This study demonstrates the potential of miRNA for PMI estimation in advanced stages of death. In this study, miRNA-195, miRNA-206, and miRNA-378 were selected as target miRNAs and miRNA-1 as reference miRNA. Left ventricle tissue (5 g) of the heart from 20 forensic autopsies of traffic accident victims (18-32 years) were collected and processed. The samples were held at room temperature for eight different time intervals (12, 24, 48, 72, 96, 120, 168 and 196 h), and RNA was extracted from all the samples using Trizol-based RNA isolation protocol, followed by cDNA synthesis and amplification with commercially available specific miRNA probes in Real-Time PCR (RT-PCR), Ct was calculated. The result showed that miRNAs were associated with PMI. Over time, there were substantial changes in the Ct values of all three miRNAs, with significant reductions observed at 196 h compared to 12 h. miRNA-206 demonstrated significant changes at multiple time intervals, while miRNA-1 remained stable for up to 196 h and thus holds caas an endogenous marker. In conclusion, miRNA has the potential to serve as a valuable tool for estimating PMI, especially during the advanced stages of decomposition, when used in conjunction with established techniques. However, further validation of the study is required to obtain more accurate estimates of PMI.

Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome.

Isaacs syndrome is a disease characterized by nerve hyperexcitability and pseudomyotonia and treated with immunomodulatory and symptomatic therapy approaches. Here, we report a case of anti-(leucine-rich glioma-inactivated 1) antibody-positive patient diagnosed as Isaacs syndrome and accomplished a nearly complete response to only four sessions of therapeutic plasma exchange (TPE). Our experience suggests that TPE along with other immunomodulatory agents may be beneficial and well-tolerated approach in patient with Isaacs syndrome.

Comprehensive Analysis of the Effect of Maternal and Paternal Demographics and Lifestyle Factors on the Embryo Quality and In Vitro Fertilization Outcomes: A Retrospective Study in North Eastern India.

Background Lifestyle habits and demographic characteristics are strongly associated with sperm and oocyte quality and are important co-variates in fertility. However, their effect on the pre-implantation embryo quality in in vitro fertilization (IVF) has not been explored widely. The present retrospective study aimed to explore the effect of maternal and paternal demographic and lifestyle factors on the pre-implantation embryo quality in IVF. Methodology Women in the age group of 21 to 40 years undergoing IVF (n=105) in the Department of Reproductive Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, and their partners were recruited in the study. Maternal and paternal charts were reviewed, and the demographic, lifestyle habit related data, and data related to oocyte retrieval, oocyte quality, and embryo quality were retrieved in a predesigned spreadsheet. Appropriate statistical analysis was conducted using SPSS Version 21 to evaluate the association of the studied maternal and paternal factors with oocyte and embryo quality. P-values less than 0.05 were considered to be significant. Results Maternal factors such as tubal blockage (p=0.02) and residence in an industrial locality (p=0.001) were found to be significantly associated with the quality of oocytes. None of the maternal factors studied were associated with embryo quality; however, day 3 and day 5 embryo quality was significantly associated with educational status of the male partners (p=0.02), smoking (p=0.05), and chewing tobacco (p=0.01). Day 5 embryo quality was also associated with residence in an industrial locality of the male partners (p=0.04). Conclusions Paternal lifestyle habits such as smoking, chewing tobacco, and demographic characteristics such as education and proximity to an industrial area were all related to poor embryo quality. Maternal factors such as tubal blockage and residence of industrial locality were found to be significantly associated with the quality of oocytes.

Reflected near-infrared photography: Digging deeper into post-mortem examination.

AIM: This research aims to investigate the utility of the Near Infra-Red (NIR) photographic technique in visualizing forensic evidence in a post-mortem examination. MATERIAL AND METHODS: A total of twenty-six deceased (male: n = 15; female: n = 11) were brought to the Mortuary of King George's Medical University, Chowk, Lucknow, Uttar Pradesh, India (226003), and were used to investigate the applicability of the human visible spectrum (HVS) & near-infrared photography. In the investigation, a modified Nikon D5300 crop-framed digital single-lens reflex camera was used for NIR Photography in combination with a Micro-Nikkor 105 mm, f/2.8, (Nikon Inc., Melville, NY, USA), Hoya R72 (760nm-860nm) infrared filter and a Nikon D5600 crop-framed digital single-lens reflex camera in combination with Nikkor 50mm lens for Human Visible Spectrum (HVS) Photography. RESULTS: The finding of the study reported that the application of the NIR photography would be the best of the investigative techniques for visualization and photo-documentation of forensically relevant post-mortem findings, such as - trace evidences (e.g., blood spots & soil particles on dark clothing), in external findings (e.g., contusion on victim's body) also for internal findings in a road traffic accident (RTA), gunshot, and drowning victim (e.g., mud particles in the trachea of drowning victim & localizing contusion of the scalp in road traffic accident cases). CONCLUSION: Human visible spectrum (HVS) photographs taken with Nikon D5600 provides substantial evidence for documentation purpose, the best results for trace evidence & contusion visualization in Post-mortem examination of the deceased were achieved with the NIR Photography in combination with indirect sunlight & room light as an infrared light source. (At a wavelength of 760nm-860nm).

Acute Methanol Toxicity: Clinical Correlation with Autopsy Findings, a Descriptive Study.

BACKGROUND: Methyl alcohol poisoning or deaths from drinking illegally brewed cheap alcohol which is often spiked with chemicals to increase its potency are frequent in India. Many outbreaks from different parts of the country have been reported from time to time. A total of 11,830 lives were lost between 2006 and 2015 due to the consumption of spurious liquor in the country. The symptoms can range from mild to severe depending upon factors like the amount of exposure and time of presentation. AIMS AND OBJECTIVES: The present study was designed to describe the clinical presentation, management, and outcome of the patients during a recent methanol outbreak that can form a basis for diagnosis and management. This study also highlights the salient autopsy findings and their correlation with clinical features. MATERIALS AND METHODS: It is a retrospective, descriptive study discussing clinical features of patients with methanol intoxication, their outcome, and the clinical correlation with autopsy findings of patients who succumbed to death. The study was conducted at King George's Medical University, Lucknow. The patients were enrolled from a methanol intoxication outbreak in Barabanki district on 28th May 2019 followed by a similar outbreak in Sitapur district two days later. RESULTS: A total of 33 patients were included in this study based on predefined clinical characteristics. The average amount of alcohol consumed was about 223 mL (range: 100-300 mL). The majority of patients had onset of symptoms between 12 and 24 hours. All patients had gastrointestinal symptoms, 97% of patients had visual disturbances, 91% of patients had central nervous system manifestation while frank coma was observed in 15% of patients. Decreased urine output was reported in 6% of patients. About 90% of patients had metabolic acidosis. Out of 33 patients included in this study, 30 patients were discharged in stable condition while two died and one absconded. Autopsy findings revealed marked cerebral edema and hyperemia, hyperemic heart, and congested lungs in all the patients. One patient showed putaminal necrosis which is characteristic of methanol poisoning. Kidneys in two cases were hyperemic and show parenchymal degeneration which co-relates with both patients being anuric. CONCLUSION: Methanol intoxication is a serious problem in developing countries like ours. Timely intervention is an important factor in reducing mortality among these patients. The study highlights the very important fact that methanol intoxication can be managed at the very ground level with minimal resources (as available) if intervened and recognized in time.

DNA damage, cell cycle perturbation and cell death by naphthalene diimide derivative in gastric cancer cells.

Stomach cancer causes the third-highest cancer-related deaths worldwide. Limited availability of anticancer measures with higher efficiency and low unwanted toxicities necessitates the development of better cancer chemotherapeutics. Naphthalene diimide (NDI) derivatives have gained significant attention owing to their excellent anticancer potential. We evaluated the anticancer properties of NDI derivatives, 1a and 2a in cancer cell lines and found that 1a showed higher efficacy as compared to 2a exhibiting a remarkable difference in activity upon single atom substitution of C with N. Particularly, NDI 1a showed potent inhibitory activity against gastric cancer cell line AGS with IC50 of 2.0 µM. NDI 1a induced remarkable morphological changes and reduced clonogenicity as well as the migratory ability of AGS cells. The reduction in AGS cell migration was mediated through inhibition of Tyr397 p-FAK dephosphorylation at focal adhesion points leading to enhanced attachment of cells at contact points. NDI 1a caused extensive DNA double-strand-breaks (DSBs) leading to activation of p53 and its transcriptional target p21. Reduced nuclear BRCA1 but enhanced nuclear p53BP1 foci formation upon 1a treatment suggests that DNA DSB repair is mediated through error-prone NHEJ which led to the accumulation of extensive DNA damage. Combinatorial effects mediated by interactions of 1a with double-stranded DNA through minor groove binding as well as induction of intracellular ROS exacerbated the loss of genomic integrity induced by 1a. NDI 1a mediated DNA damage-induced S phase arrest; however, cells experiencing extensive and irreparable DNA damage underwent mitochondrial apoptosis through downregulation of anti-apoptotic protein p21. Furthermore, proliferation inhibitory activity of 1a is also attributed to inhibition of ß-catenin/c-Myc axis in AGS cells with constitutively active ß-catenin pathway. In vivo toxicity analysis of 1a revealed minimal systemic toxicity suggesting that compound 1a is a safe and potential candidate for the development of gastric cancer chemotherapeutics.

Therapeutic potential of p53 reactivation in prostate cancer: Strategies and opportunities.

Metastatic prostate cancer (mCaP) remains one of the leading causes of cancer-related death in men worldwide. Androgen receptor (AR) drives the progression of most of the mCaP, and hence the androgen deprivation therapy (ADT) is the first-line treatment of choice for mCaP. Although the responses of ADT and next-generation AR inhibitors initially improve the disease burden, the responses of this combinatorial drug therapy varied widely due to molecular alteration in mCaP patients. In addition to the altered AR signaling, loss of potent tumor-suppressor protein p53 exhibits poor outcomes. p53 influences cell plasticity and is frequently lost in more aggressive prostate cancer (CaP) with neuroendocrine differentiation. Loss of p53 antagonizes the effect of AR inhibitors and enhances the proliferation rate of CaP cells. Considering the important role of p53 inactivation in cancer development, restoration of wild-type p53 function by p53-reactivating compounds developed with different approaches, seems to be an attractive therapeutic strategy for prostate cancer therapy. In this review, we discuss the therapeutic potential of these compounds with a particular focus on the pharmacological rescue of p53 in mCaP. In addition, we also highlight the challenges and new opportunities of p53-targeted therapy for the future.

SPART: A versatile and standardized data exchange format for species partition information.

A wide range of data types can be used to delimit species and various computer-based tools dedicated to this task are now available. Although these formalized approaches have significantly contributed to increase the objectivity of species delimitation (SD) under different assumptions, they are not routinely used by alpha-taxonomists. One obvious shortcoming is the lack of interoperability among the various independently developed SD programs. Given the frequent incongruences between species partitions inferred by different SD approaches, researchers applying these methods often seek to compare these alternative species partitions to evaluate the robustness of the species boundaries. This procedure is excessively time consuming at present, and the lack of a standard format for species partitions is a major obstacle. Here, we propose a standardized format, SPART, to enable compatibility between different SD tools exporting or importing partitions. This format reports the partitions and describes, for each of them, the assignment of individuals to the "inferred species". The syntax also allows support values to be optionally reported, as well as original trees and the full command lines used in the respective SD analyses. Two variants of this format are proposed, overall using the same terminology but presenting the data either optimized for human readability (matricial SPART) or in a format in which each partition forms a separate block (SPART.XML). ABGD, DELINEATE, GMYC, PTP and TR2 have already been adapted to output SPART files and a new version of LIMES has been developed to import, export, merge and split them.

Advances in Cancer Therapeutics: Conventional Thermal Therapy to Nanotechnology-Based Photothermal Therapy.

In this review, advancement in cancer therapy that shows a transition from conventional thermal therapies to laser-based photothermal therapies is discussed. Laser-based photothermal therapies are gaining popularity in cancer therapeutics due to their overall outcomes. In photothermal therapy, light is converted into heat to destruct the various types of cancerous growth. The role of nanoparticles as a photothermal agent is emphasized in this review article. Magnetic, as well as non-magnetic, nanoparticles have been effectively used in the photothermal-based cancer therapies. The discussion includes a critical appraisal of in vitro and in vivo, as well as the latest clinical studies completed in this area. Plausible evidence suggests that photothermal therapy is a promising avenue in the treatment of cancer.

The Effect of Ascophyllum nodosum Extract on the Nutraceutical Antioxidant Potential of Vigna radiata Sprout under Salt Stress.

Mung bean (Vigna radiata L.) sprout is a popular fresh vegetable, tasty and high in antioxidants. To increase yield and quality after the occurrence of both abiotic and biotic stresses, the application of seaweed extracts is of great importance. Hence, this study was conducted to determine the effect of Ascophyllum nodosum extract (ANE) in the presence of salt on the antioxidant potential of V. radiata sprouts. Different concentrations of ANE viz. 0.00, 0.01, 0.05, 0.10, and 0.50% and NaCl 0, 25, 50, 75, and 100 mM alone and in combinations were tested for researching the antioxidant potential of V. radiata sprouts at 0, 24, and 36 h of sprouting. The DPPH free-radical-scavenging activity of sprouts of V. radiata was found to increase with time and peaked at 24 h of treatment. The A. nodosum extract (0.01%) could reverse the ill effect of the low level of salinity posed by up to 25 mM NaCl. The increasing salinity deteriorated the antioxidant activity using ABTS method of sprouts down to 20.45% of the control at 100 mM NaCl. The total phenolic content (TPC), total flavonoid content (TFC), and reducing power of V. radiata sprouts was found to increase till 36 h of sprouting. A slight increase in TPC, TFC and reducing power was observed when seeds were treated with low concentrations of ANE. The elevation in TPC, TFC and reducing power upon treatment with low concentrations of ANE was also noticed in sprouts in saline combinations. Alpha amylase inhibition activity was found to reach a (67.16% ± 0.9) maximum at 24 h of sprouting at a 0.01% concentration of ANE. Tyrosinase inhibition and alpha glucosidase inhibition was 88.0% ± 2.11 and 84.92% ± 1.2 at 36 h of sprouting, respectively, at 0.01% concentration of ANE. A. nodosum extract is natural, environmentally friendly, and safe, and could be used as one of the strategies to decline stress at a low level and enhance the antioxidant activities in V. radiata sprouts, thus increasing its potential to be developed as an antioxidant-based functional food.

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease.

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.