Zinc-loaded mesoporous silica nanoparticles mitigate salinity stress in wheat seedlings through silica-zinc uptake, osmotic balance, and ROS detoxification.

Abiotic stresses like salinity and micronutrient deficiency majorly affect wheat productivity. Applying mesoporous silica nanoparticles (MSiNPs) as a smart micronutrient delivery system can facilitate better stress management and nutrient delivery. In this purview, we investigated the potential of MSiNPs and Zn-loaded MSiNPs (Zn-MSiNPs) on the growth and physiology of wheat seedlings exposed to salinity stress (200 mM NaCl). Initially, the FESEM, DLS, and BET analysis portrayed nanoparticles' spherical shape, nano-size, and negatively charged mesoporous surface. A sustained release of Zn+2 from Zn-MSiNPs at 30 °C, diffused light, and pH 7 was perceived with a 96.57% release after 10 days. Further, the mitigation of NaCl stress in the wheat seedlings was evaluated with two different concentrations, each of MSiNPs and Zn-MSiNPs (1 g/L and 5 g/L), respectively. A meticulous improvement in the germination and growth of wheat seedlings was observed when treated with both MSiNPs and Zn-MSiNPs. A considerable increase in chlorophyll, total protein, and sugar content was in consort with a substantial decline in MDA, electrolyte leakage, and ROS accumulation, showcasing the nanomaterials' palliating effects. Most importantly, the K+/Na+ ratio in shoots increased significantly by 3.43 and 4.37 folds after being treated with 5 g/L Zn-MSiNPs, compared to their respective control sets (0 and 200 mM NaCl). Therefore, it can be concluded that the Zn-MSiNPs can effectively restrain the effects of salinity stress on wheat seedlings.

Fabrication and optimization of extended-release beads of diclofenac sodium based on Ca++ cross-linked Taro (Colocasia esculenta) stolon polysaccharide and pectin by quality-by-design approach.

The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro (Colocasia esculenta) stolon polysaccharide (TSP) with 23 full factorial design. Total polysaccharide concentration (TPC), polysaccharide ratio (PR), and cross-linker concentration ([CaCl2]) were taken as independent factors with two levels of each. Initially, TSP was extracted, purified, and characterized. Fourier-transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed drug-polymer compatibility. The study also revealed the significant positive effect of TSP on drug entrapment efficiency (DEE) and sustaining drug release. The response variables (DEE, cumulative % drug-release at 1, 2, 4, 6, and 10 h, release-constant, time for 50 % and 90 % drug release (T50%, T90%), release-similarity factor (f2), and difference factor (f1) were analyzed, and subsequently, independent fabrication variables were numerically optimized by Design-Expert software (Version-13; Stat-Ease Inc., Minneapolis). The optimized batch exhibited appreciable DEE of 88.5 % (± 2.2) and an extended-release profile with significantly higher T50%, T90%, and release-similarity factor (f2) of 4.7 h, 11.4 h, and 71.6, respectively. Therefore, the study exhibited successful incorporation of the novel TSP as a potential alternative adjunct polysaccharide in the pectin-based ion-cross-linked inter-penetrating polymeric network for extended drug release.

Green synthesis of copper nanoparticles by using pineapple peel waste: in vitro characterizations and antibacterial potential.

A considerable amount of fruit waste is being produced every day worldwide. The green synthesis of metal nanoparticles from fruit peel waste can be an innovative, cost-effective, and eco-friendly alternative to traditional methods. Copper nanoparticles (CuNPs) were synthesized by a green method using the pineapple peels extract (PLX) and copper sulfate pentahydrate. The formation of CuNPs was visually identified and detected by UV-Visible spectroscopy. The CuNPs were characterized by Fourier-transform infrared (FTIR) spectroscopy, particle size analyzer, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The antioxidant and reducing power of CuNPs were conducted by %DPPH scavenging and electron transfer-based ferric reducing antioxidant power (FRAP) assay, respectively. The antibacterial properties of CuNPs were determined in gram-positive, and gram-negative bacteria. The results showed that the CuNPs were spherical in shape with mean particle size 290.5 nm. The zeta potential of the nanoparticles was found to be - 12.3 mV indicating the instability in the colloidal state. The FTIR study confirmed the peaks of phytochemicals present in the PLX and the nanoparticles supporting the use of pineapple peels as stabilizing, reducing and capping agents. Both the DPPH and reducing power assay depicted that the synthesized CuNPs had significant antioxidant activity. However, the synthesized CuNPs had strong inhibitory capacity against both gram-positive and gram-negative test organisms. Thus, the CuNPS could be used for its viable antibacterial potential to preserve fruits, flowers, and vegetables from bacterial contamination.

Formulation of silver nanoparticles using Duabanga grandiflora leaf extract and evaluation of their versatile therapeutic applications.

The current research focused on the green synthesis of silver nanoparticles (AgNPs) using Duabanga grandiflora leaf extract. The green synthesis of AgNPs was confirmed by the surface plasmon resonance band at 453 nm in a UV-Visible analysis. The formulated AgNPs had a diameter of around 99.72 nm with a spherical shape. Fourier transform infrared (FTIR) spectrum revealed the bio-reducing potential of phytochemicals present in D. grandiflora, which fundamentally influenced the synthesis of AgNPs. Zeta potential, dynamic light scattering (DLS), scanning electron microscopic (SEM), energy-dispersive X-ray spectroscopic (EDX), X-ray diffraction (XRD), and transmission electron microscopic (TEM) analyses were executed to reveal the physicochemical attributes of the AgNPs. The AgNPs were further investigated for their antioxidant, antidiabetic, anticancer, and antibacterial potential. The DPPH free radical assay revealed the potential radical scavenging capacity (IC50 = 76.73 µg/ml) of green synthesized AgNPs. α-Amylase inhibitory assay displayed significant inhibitory potential (IC50 = 162.11 µg/ml) of this starch-breaking enzyme by AgNPs, revealing the antidiabetic potential of AgNPs. AgNPs exhibited potential cytotoxic activity (IC50 = 244.57 µg/ml) against malignant human kidney cells. In addition, AgNPs showed outstanding antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains. Interestingly, AgNPs showed cytotoxic and antimicrobial activities at much higher concentrations than radical scavenging and α-amylase inhibitory concentrations. Thus, our finding elaborated the scope of green synthesized AgNPs for diverse therapeutic applications (dose-dependent) for further clinical translation.

Enhanced adaptation to salinity stress in lentil seedlings through the use of trehalose-functionalized silica nanoparticles (TSiNPs): Exploring silica-sugar absorption and oxidative balance.

Silica nanoparticles (SiNPs) confer better growth and development of plants under salinity stress. Moreover, the surface-functionalization of SiNPs with bioactive molecules is expected to enhance its efficacy. The present study thus aimed to modify the surface of SiNPs, by attaching a bioactive molecule (trehalose) to obtain TSiNPs. The successful surface functionalization was confirmed using FTIR, XRD, and EDS. The spherical shape and amorphous nature of the nanoparticles were confirmed using SEM. The TEM image analysis revealed that the size of SiNPs and TSiNPs ranged between 20-50 nm and 200-250 nm, respectively. A novel bioassay experiment designed to study the release of silica and trehalose from nanoparticles elucidated that the TSiNPs improved the release and uptake of silica. Also, trehalose uptake significantly improved after 72 h of application due to enhanced release of trehalose from TSiNPs. Further, this study also aimed to investigate the potential benefits of SiNPs and TSiNPs in promoting the growth and development of plants under salinity stress. In this context, the nanoparticles were applied to the saline-stressed (0, 200, 300 mM) lentil seedlings for the in-planta experiments. The results revealed that both SiNPs and TSiNPs improved the growth of seedlings (shoot, and root length), ionic balance (K+/Na+ ratio), and osmolyte status (sugars, proline, glycine betaine, trehalose). Additionally, increased antioxidant enzyme activities helped scavenge ROS (H2O2, O2.-) generated in NaCl-stressed seedlings, ultimately improving the membrane integrity (by reducing MDA and EL). However, the TSiNPs exhibited a much-enhanced activity in stress alleviation compared to the SiNPs.

Papaya peel extract-mediated green synthesis of zinc oxide nanoparticles and determination of their antioxidant, antibacterial, and photocatalytic properties.

This study describes an effective and eco-friendly approach to the synthesis of zinc oxide nanoparticles (ZnONPs) utilizing papaya fruit peel extract (PPE). The structural evaluation and morphological features of synthesized ZnONPs were examined using various physicochemical analyses. The formulated ZnONPs were spherical to hexagonal in shape with ⁓ 170 nm in diameter. ZnONPs exhibited improved antioxidant potential in terms of DPPH radical scavenging activity (IC50 = 98.74 µg/ml) and ferric-reducing potential compared with PPE. The antibacterial activity of ZnONPs was measured against pathogenic strains of Salmonella typhi, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The biosynthesized ZnONPs showed potential antibacterial efficacy against all microbes. In addition, ZnONPs exhibited potential photocatalytic activity in rhodamine B degradation in the presence of sunlight. The results indicated that papaya peels, which are these fruit wastes, could be helpful for the green synthesis of ZnONPs with good dose-responsive antioxidant, antibacterial, and photocatalytic activities.

Nanomedicines for the management of diabetic nephropathy: present progress and prospects.

Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN.

Evaluation of Cassia fistula seed galactomannan as tablet-binder in formulation of diclofenac sodium-loaded monolithic matrix tablet.

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder.

Evaluation of maceration, microwave, ultrasound-assisted extraction methods on free, esterified and bound phenolic profile and antioxidant activity of black rice.

Black rice (Oryza sativa L.) is a rich source of phenolics and anthocyanins. It was aimed to investigate the effect of different extraction methods such as conventional solvent extraction, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE) on antioxidant activity and phenolic profiling of black rice free, esterified, and bound phenolics fractions. Spectrophotometric methods were used to evaluate antioxidant activity and HPTLC was used for phenolics profiling. The highest content of % yield, total anthocyanin (TAC), total phenolic (TPC), and total flavonoid (TFC) contents were detected in MAE. It was also observed that antioxidant activity based on DPPH, ABTS, superoxide radical-scavenging and ferric reducing antioxidant power (FRAP) assays showed highest activity in MAE. Eight phenolic compounds were identified and quantified by a validated HPTLC method. MAE showed most abundant phenolic compounds. A significant positive correlation was established between % yield, total phenolic content, and total flavonoid content (p < 0.05) where a significant negative correlation was established between % yield, TPC, and TFC with IC50 of antioxidant activity (p < 0.05). Diverse phenolic contents and antioxidant activity were studied with different forms of phenolics with the different extraction methods. It designates that the extraction techniques had effects on the bioactive compounds as well biological properties.

Preparation of silver nanoparticles by Osbeckia stellata aqueous extract via green synthesis approach: Characterization and assessment of their antioxidant, antidiabetic, cytotoxicity, and antibacterial properties.

Silver nanoparticles (Ag NPs) via green synthesis using medicinal plants have been widely used in natural product research due to the economical and eco-friendly properties of NPs. The plant-derived Ag NPs biosynthesis comprises the interaction between silver nitrate (precursor) and bioactive components of plant extract (reducing agents). In this work, Ag NPs were biosynthesized using Osbeckia stellata leaves aqueous extract. Characterization of Ag NPs was done by using ultraviolet-visible absorption (UV-Vis) spectroscopy, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray analysis (EDX). Further, antioxidant, antidiabetic, cytotoxicity, and antimicrobial activities were evaluated to establish the pharmacological properties of Ag NPs. UV-Vis spectroscopy and FTIR showed an absorption peak of Ag NPs due to the surface plasmonic resonance. In contrast, the particle size in the nanometer range was analyzed by XRD and DLS. The size of the particle was confirmed by the SEM, TEM, and EDX in the nanometer range. This study showed the spherical shape and crystalline nature of NPs. Zeta potential was used to determine the stability of Ag NPs. Biosynthesized Ag NPs showed significantly potent antioxidant, antidiabetic, and cytotoxicity activity. Ag NPs also showed effectiveness against gram-positive (Escherichia coli) and gram-negative (Staphylococcus aureus) bacteria in the antimicrobial activity study. The result concluded that these Ag NPs might be used in biomedical and pharmacological fields.

A Comprehensive View(COUP D'OEIL) of Brain Tumors from Eastern India.

BACKGROUND: Brain tumors have always fascinated and intrigued histopathologists due to their diverse morphology and rarity. Recent surge in the molecular developments has further posed a challenge in diagnosis especially in a resource limited setting. Therefore, comprehensive tumor registries have become quintessential to compare our existing database with new found knowledge. METHODS: A descriptive retrospective study was carried out on archival data of 5 years in a neuroscience institute. All neurosurgical cases operated with complete clinical history and definitive histopathological diagnosis were included. The cases were analyzed with reference to age, sex, location of the lesion, grade of the tumor, and immunohistochemical profile as available and compared with existing registries and literature. RESULTS: The primary brain tumors accounted for 38.29% of all pathologies. Majority of cases clustered around 40-70 years of age (65%). Pediatric (0-19 years) cases comprised 7%. Most common primary brain tumor found in the adult population was meningioma (28%) followed by Glioblastoma (25%). The most common neoplasm in pediatric age group were gliomas (46.29%) followed by embryonal neoplasms. Pituitary adenomas (PAs) constituted 16% of all intracranial neoplasm. Gonadotroph adenoma was the most common of the nonfunctional adenomas constituting one half of the PAs (51.72%). Somatotroph adenoma was most common in the functional group constituting 20% of all PAs. CONCLUSIONS: The layout of cases when compared with available brain tumor registries showed nearly similar trends in distribution. Our study succored data from the population in eastern part of India of which our institute is a major referral centre for neurosurgical cases.

Label-Free Detection of Epinephrine Using Flower-like Biomimetic CuS Antioxidant Nanozymes.

A biosensor comprising crystalline CuS nanoparticles (NPs) was synthesized via a one-step simple coprecipitation route without involvement of a surfactant. The powder X-ray diffraction method has been used to evaluate the crystalline nature and different phases consist of the formation of CuS NPs. Mainly hexagonal unit cells consist of the formation of CuS NP unit cells. Most of the surfaces are covered with rhombohedral microparticles with a smooth exterior and surface clustering, examined by SEM images, and the shape of NPs was spherical, having an average size of 23 nm, as confirmed by TEM analysis. This study has focused on the peroxidase-mimicking activity, superoxide dismutase (SOD)-mimicking activity, and chemosensor-based colorimetric determination and detection of epinephrine (EP) neurotransmitters with excellent selectivity. The CuS NPs catalyzed the oxidation of the oxidase substrate 3, 3-5, 5 tetramethyl benzidine (TMB) with the help of supplementary H2O2 that followed Michaelis-Menten kinetics with excellent Km and Vmax values calculated by the Lineweaver-Burk plot. Taking advantage of the drop in absorbance upon introduction of EP for the CuS NPs-TMB/H2O2 system, a colorimetric route has been developed for selective and real-time detection of EP. The sensitivity of the new colorimetric probe was vibrant, having a linear range of 0-16 µM, and achieved a low limit of detection of 457 nM. Moreover, the present nanosystem exhibited appreciable SOD-mimicking activity which could effectively remove O2•- from commercial cigarette smoke, along with it acting as a potential radical scavenger as well. The new nanosystem effectively scavenged •OH, O2.-, and metal chelation which were investigated calorimetrically.

Impact of ultrasound-assisted extraction of polyphenols and caffeine from green tea leaves using high-performance thin-layer chromatography.

Tea is the most popular daily drink consumed globally, with a high concentration of caffeine and polyphenols. In this study, the effects of ultrasonic-assisted extraction and quantification of caffeine and polyphenols from green tea were investigated and optimized using 23 -full factorial design and high-performance thin-layer chromatography. Three parameters were optimized to maximize the concentration of caffeine and polyphenols extracted using ultrasound: crude drug-to-solvent ratio (1:10-1:5), temperature (20-40°C), and ultrasonication time (10-30 min). The optimal conditions achieved from the model for tea extraction were as follows: crude drug-to-solvent ratio, 0.199 g/ml; temperature, 39.9°C; and time, 29.9 min; the extractive value was found to be 16.8%. Images from scanning electron microscopy showed that the matrix underwent a physical alteration and cell wall disintegration, which intensified and accelerated the extraction. This process might be simplified using sonication, which results in a higher extractive yield and a significant concentration of caffeine and polyphenols than the traditional approach, with a smaller quantity of solvent and faster analytical times. The result of high-performance thin-layer chromatography analysis proves a significant positive correlation between extractive value and caffeine and polyphenol concentrations.

Green synthesis of silver nanoparticles using Eupatorium adenophorum leaf extract: characterizations, antioxidant, antibacterial and photocatalytic activities.

The green synthesis of metallic nanoparticles has tremendous impacts in various fields as found in recent years due to their low cost, easy and environmentally friendly synthesis. In this article, we report a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using an aqueous Eupatorium adenophorum (E. adenophorum) leaf extract as a bioreductant. Interestingly, Fourier transform infrared (FTIR) spectroscopy analysis established that the E. adenophorum extract not only served as a bioreductant but also acted as a capping agent to stabilize the nanoparticles by functionalizing the surfaces. Various characterization techniques were adopted, such as X-ray powder diffraction (XRD), FTIR, ultraviolet-visible absorption (UV-Vis) spectroscopy, dynamic light scattering, scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDX) to analyze the biosynthesized AgNPs. Biosynthesized nanoparticles were also explored for antioxidant, antibacterial and photocatalytic activities. The AgNPs showed improved free radical scavenging activity (IC50 48.96 ± 0.84 µg/mL) and bacterial inhibitory effects against both gram-positive (Staphylococcus aureus; 64.5 µg/mL) and gram-negative (Escherichia coli; 82.5 µg/mL) bacteria. Photocatalytic investigation showed AgNPs were effective at degrading rhodamine dye (78.69% in 90 min) when exposed to sunlight. These findings collectively suggest that E. adenophorum AgNPs were successfully prepared without the involvement of any hazardous chemical and it may be an effective antibacterial, antioxidant and promising agent for the removal of hazardous dye from waste water produced by industrial dyeing processes.

Tissue specific changes of phytochemicals, antioxidant, antidiabetic and anti-inflammatory activities of tea [Camellia sinensis (L.)] extracted with different solvents.

Different parts of Camellia sinensis (L.) were extracted with solvents according to polarity, and the extracts' phytochemical profiling and biological activities were examined. The total phenolic (TPC) and total flavonoid (TFC) contents increased with the increasing polarity of the solvent which met its maximum in polar solvents. The increasing antioxidant, anti-inflammatory and antidiabetic activities were recorded with increasing polarity of solvents which showed hydroalcoholic as best solvent. The strong and significant correlation was among the TPC, TFC, DPPH, anti-inflammatory and antidiabetic activities for different parts of tea. HPTLC study of individual phenolic acids, epigallocatechin gallate, gallocatechin and theaflavin met their maximum level of content with polar solvents like hydroalcohol, methanol and water mostly in mainly tea leaves. Our finding suggested that the polar solvents and young leaves of tea were beneficial for obtaining extracts. On the other hand, phenolics were found to be potent antioxidant, anti-inflammatory and antidiabetic agent.

Molecular Mechanisms of Action of Eugenol in Cancer: Recent Trends and Advancement.

BACKGROUND: Cancer is, at present, among the leading causes of morbidity globally. Despite advances in treatment regimens for cancer, patients suffer from poor prognoses. In this context, the availability of vast natural resources seems to alleviate the shortcomings of cancer chemotherapy. The last decade has seen a breakthrough in the investigations related to the anticancer potential of dietary phytoconstituents. Interestingly, a handsome number of bioactive principles, ranging from phenolic acids, phenylpropanoids, flavonoids, stilbenes, and terpenoids to organosulphur compounds have been screened for their anticancer properties. Among the phenylpropanoids currently under clinical studies for anticancer activity, eugenol is a promising candidate. Eugenol is effective against cancers like breast, cervical, lung, prostate, melanomas, leukemias, osteosarcomas, gliomas, etc., as evident from preclinical investigations. OBJECTIVE: The review aims to focus on cellular and molecular mechanisms of eugenol for cancer prevention and therapy. METHODS: Based on predetermined criteria, various scholarly repositories, including PubMed, Scopus, and Science Direct were analyzed for anticancer activities of eugenol. RESULTS: Different biochemical investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule. A survey of current literature has unveiled the molecular mechanisms intervened by eugenol in exercising its anticancer role. CONCLUSION: Based on the critical analysis of the literature, eugenol exhibits vivid signaling pathways to combat cancers of different origins. The reports also depict the advancement of novel nano-drug delivery approaches upgrading the therapeutic profile of eugenol. Therefore, eugenol nanoformulations may have enormous potential for both the treatment and prevention of cancer.

Probiotics: Evolving as a Potential Therapeutic Option against Acetaminophen-Induced Hepatotoxicity.

Acetaminophen (APAP) is the most common prescription medicine around the world for the treatment of pain and fever and is considered to be a safe drug at its therapeutic dose. However, a single overdose or frequent use of APAP can cause severe acute liver injury. APAP hepatotoxicity is a prevalent cause of acute liver disease around the world and the lack of suitable treatment makes it a serious problem. In recent years, there has been a surge in interest in using probiotics and probiotic-derived products, known as postbiotics, as health and disease negotiators. A growing body of evidence revealed that they can be equally effective against APAP hepatotoxicity. Different probiotic bacteria were found to be pre-clinically effective against APAP hepatotoxicity. Different postbiotics have also shown exciting results in preclinical models of APAP hepatotoxicity. This review summarized the protective roles and mechanisms of the different probiotic bacteria and postbiotics against APAP hepatotoxicity, with critical discussion. A brief discussion on potential novel probiotics and postbiotics for oxidative liver injury was also included. This review was written in an attempt to pique the interest of researchers in developing a safe therapeutic option against oxidative liver damage using probiotics and/or postbiotics as dietary supplements.

In Silico Integration of Transcriptome and Interactome Predicts an ETP-ALL-Specific Transcriptional Footprint that Decodes its Developmental Propensity.

Early T precursor acute lymphoblastic leukemia (ETP-ALL) exhibits poor clinical outcomes and high relapse rates following conventional chemotherapeutic protocols. Extensive developmental flexibility of the multipotent ETP-ALL blasts with considerable intra-population heterogeneity in terms of immunophenotype and prognostic parameters might be a target for novel therapeutic interventions. Using a public gene expression dataset (GSE28703) from NCBI GEO DataSets with 12 ETP-ALL and 40 non-ETP-ALL samples, such heterogeneity was found to be reflected in their transcriptome as well. Hub genes were identified from the STRING-derived functional interaction network of genes showing differential expression between ETP-ALL and non-ETP-ALL as well as variable expression across ETP-ALL. Nine genes (KIT, HGF, NT5E, PROM1, CD33, ANPEP, CDH2, IL1B, and CXCL2) among the hubs were further validated as possible diagnostic ETP-ALL markers using another gene expression dataset (GSE78132) with 17 ETP-ALL and 27 non-ETP-ALL samples. Linear dimensionality reduction analysis with the expression levels of the hub genes in ETP-ALL revealed their divergent inclinations towards different hematopoietic lineages, proposing them as novel indicators of lineage specification in the incompletely differentiated ETP-ALL blasts. This further led to the formulation of a personalized lineage score calculation algorithm, which uncovered a considerable B-lineage-bias in a substantial fraction of ETP-ALL subjects from the GSE28703 and GSE78132 cohorts. In addition, STRING-derived physical interactome of the potential biomarkers displayed complete segregation of the B-lineage-skewed markers from other lineage-associated factors, highlighting their distinct functionality and possible druggability in ETP-ALL. A panel of these biomarkers might be useful in pinpointing the dominant lineage specification programmes in the ETP-ALL blasts on a personalized level, urging the development of novel lineage-directed precision therapies as well as repurposing of existing therapies against leukemia of different hematopoietic lineages; which might overcome the drawbacks of conventional chemotherapy.

Protective effect of probiotics against acetaminophen induced nephrotoxicity.

Acetaminophen (APAP) is commonly prescribed as an antipyretic and analgesic agent in the practical field. Like every other drug(s), APAP also undergo metabolism by oxidation or conjugation by glucuronate and sulphate to form the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the NAPQI is detoxified by conjugation with reduced glutathione (GSH). Interestingly, APAP is also metabolized in the kidney by deacetylation reaction in the presence of N-deacetylase enzyme into another severely toxic but minor metabolite, p-aminophenol. Both NAPQI and p-aminophenol shows nephrotoxicity as well as hepatotoxicity. Hence, the long-term therapeutic dose use and unnecessary overdose of APAP are of great concern as prolonged negligence may cost the nephrotoxicity that may lead to uremia and finally to kidney failure. It has recently been investigated that probiotic supplementation inhibits the sequential events associated with APAP-induced nephrotoxicity. This review emphasizes the role of different probiotics that have already been investigated in nephrotoxicity or uremia caused by APAP overdose.