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This review summarizes the impact of systemic and ocular inflammatory disorders on diabetes mellitus (DM) and diabetic retinopathy (DR). Local inflammation is a key pathology in diabetic retinopathy (DR) and is also an evolving target for clinical therapy. The legacy effects of local inflammation at the intracellular level make DR a persistent self-driven vicious process. Ocular inflammation is accompanied as well as incited by systemic inflammation due to diabetes mellitus (DM) itself. Over the years, a multitude of studies have evaluated the impact of systemic inflammatory disorders (SIDs, like rheumatoid arthritis, lupus, psoriasis, etc.) and anti-inflammatory drugs prescribed for managing them on manifestations of DM. Recent studies have indicated increased insulin resistance to be a result of chronic inflammation, and the anti-inflammatory drugs to have a protective effect towards DM. Very few studies have evaluated the impact of SIDs on DR. Furthermore, the evidence from these studies is conflicting, and while local anti-inflammatory therapy has shown a lot of clinical potential for use in DR, the results of systemic anti-inflammatory therapies have been inconsistent. The impact of local ocular inflammation due to uveitis on DR is a crucial aspect that has not been evaluated well at present. Initial pre-clinical studies and small-sized clinical reports have shown a strong and positive relationship between the presence of uveitis and the severity of DR as well as its progression, while larger cross-sectional patient surveys have refuted the same. The long term impact of ocular inflammation due to uveitis on DR needs to be studied while adjusting for confounders. [ABSTRACT FROM AUTHOR]

Purpose: Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good‑quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12–24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real‑time polymerase chain reaction (PCR). Settings and Design: Prospective study. Methods: Retina tissues were separated from the donor/ enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at ‑80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal‑specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures. Statistical Analysis: The data were calculated as an average of normalised Ct values ± standard error of the mean. Results: RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal‑specific genes such as PAX6, RHO, TUBB3, CRX, and ALDH1L1. The primary cultures established from cadaveric tissues showed viable cells. Conclusion: The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling. [ABSTRACT FROM AUTHOR]

Antifungal azole drugs like fluconazole, itaconazole and ketoconazole are widely used for treatment of fungal related diseases including aspergillosis and mucormycosis. This study aimed at biosynthesis of fluconazole, itaconazole and ketoconazole containing oil/water (O/W) nanoemulsions (NE) using Eucalyptus essential oil and its effect against aspergillosis and mucormycosis. Nanoemulsions were synthesized having eucalyptus essential oil, surfactants: tween 80, and co-surfactant: ethanol. Zeta potential, pH, conductivity and droplet size of nano-formulations were studied by using Zeta sizer. Nanoemulsions were analyzed by UV–VIS, FT-IR and fluorescent techniques. Stability studies were conducted by storing the nanoemulsions at different conditions for 60 days. Anti-aspergillosis, anti-mucormycosis and drug release pharmokinetics were evaluated. Average size of nanoemulsions ranged from 245 to 415 nm along with zeta potential from − 9.20 to − 25.4 mV. Encapsulation efficiency of drug loaded nanoemulsions was ranged from 40 to 50%. Nano-droplets displayed stability after 60 days of storage. Considerable anti-aspergillosis and anti-mucormycosis activities were detected. Among all formulations, F1NEs depicted high antifungal activity against Aspergillus strains MTCC 277, MTCC 343 as observed by zone of inhibition (ZOI) values. Against Mucor spp strain MTCC 3373, visual pictures clearly showed substantial inhibition in fungal growth. Pharmokinetic study shown that all nanoformulations showed Korsmeyer–Peppas model. [ABSTRACT FROM AUTHOR]

The response of retinal pathology to interventions in diabetic retinopathy (DR) is often independent of the glycated hemoglobin (HbA1c) values at the point of care. This is despite glucose control being one of the strongest risk factors for the development and progression of DR. Previous preclinical and clinical research has indicated metabolic memory, whereby past cumulative glucose exposure may continue to impact DR for a prolonged period. Preclinical studies have evaluated punitive metabolic memory through poor initial control of DM, whereas clinical studies have evaluated protective metabolic memory through good initial control of DM. In this narrative review, we evaluate the preclinical and clinical evidence regarding metabolic memory and discuss how this may form the basis of preventive care for DR by inducing “metabolic amnesia” in people with a history of uncontrolled diabetes in the past. While our review suggested mitochondrial biology may be one such target, research is still far from a possible clinical trial. We discuss the challenges in such research. [ABSTRACT FROM AUTHOR]

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX. [ABSTRACT FROM AUTHOR]

Essential oil from Rosmarinus officinalis (also known as rosemary essential oil) is used as traditional medicine and used as therapeutic in medicine, food, and cosmetic sectors. However, this oil is highly unstable, volatile, and prone to oxidation which limits its use. Thus, encapsulation is the better way to protect this oil from adverse conditions. The objective of this study was synthesis of rosemary essential oil (REO) based O/W (oil/water) nanoemulsions (designated as RNE) and evaluation of its biological potential. Physiological characterization was carried out using, UV, fluorescent, and FT-IR techniques. Various biological activities such as anticancerous, antidiabetic, and anti-inflammatory were also estimated. Pharmacokinetics studies on RNE were carried out. Encapsulation efficiency of RNE was found to be 92%. RNE nanoemulsions were spherical in shape with globule size, Z-Average (nm) size 220 nm, zeta potential −11.33 mV, and polydispersity index was 0.47. RNE nanoemulsions were stable even after 50 days of storage at different temperatures. Antioxidant potential of RNE was conducted by various assays and IC50 were DPPH free radical scavenging activity: 21.53, nitric oxide radical scavenging activity: 26.66, hydroxyl radical scavenging activity: 32.69, ABTS radical scavenging activity: 33.05, and iron chelating assay: 38.78. Notable anticancer activity was observed with the percent cell viability of HeLa cells after treatment with RNE was 23% at higher concentration of 5 μg. Antidiabetic study revealed that RNE inhibited α-amylase in a concentration dependent manner, with 71% inhibition at its higher concentration of 250 μg. RNE depicted maximum antibacterial activity against Bacillus subtilis at higher concentration of 300 μg. Drug kinetic study revealed that nanoemulsions exhibited Korsmeyer–Peppas model. Based on this, the possible role of R. officinalis oil-based nanoemulsions in food, cosmetic, and pharma sectors has been discussed. [ABSTRACT FROM AUTHOR]

Essential oil from Melaleuca alternifolia (also known as Tea tree essential oil, TTO) is used as traditional medicine and used as therapeutic in medicine, food and cosmetic sectors. However, this oil is highly unstable, volatile and prone to oxidation which limits its practical use. The objective of this study was synthesis of tea tree oil based O/W (oil/water) nanoemulsions (tea tree essential oil nanoemulsions, TNE) and evaluation of its biological potential. Physiological characterization was carried out using UV, fluorescent, and FT-IR techniques. Various biological activities such as anticancerous, antidiabetic and anti-inflammatory were also estimated. Pharmacokinetics study on TNE was carried out. Encapsulation efficiency of nanoemulsions was found to be 83%. Nanoemulsions were spherical in shape with globule size 308nm, zeta potential -9.42 and polydispersity index was 0.31. Nanoemulsions were stable even after 50days of storage at different temperatures. Anti-oxidant potential of TNE was conducted by various assays and IC50 were: Nitric oxide radical scavenging activity:225.1, DPPH radical scavenging activity:30.66, Iron chelating assay:38.73, and Iron reducing assay:39.36. Notable anticancer activity was observed with the percent cell viability of HeLa cells after treatment with 1, 2 and 5µl of TNE was 82%, 41% and 24%, respectively. Antidiabetic study revealed that TNE inhibited -amylase in a dose-dependent manner, with 88% inhibition at its higher volume of 250µl. Drug kinetic study revealed that nanoemulsions exhibited first-order model. Based on this, the possible role of M. alternifolia oil-based nanoemulsions in cosmetic, food, and pharma sectors has been discussed. [ABSTRACT FROM AUTHOR]

Melaleuca is a well-known genus of the Myrtaceae family, one of the major plant families with a high concentration of essential oils. The Australian tea tree (Melaleuca alternifolia), a genus of aromatic and herbaceous trees that belongs to the Myrtaceae family, is well known to produce herbal essential oils owing to the presence of therapeutic and medicinal elements in the plant's by-products. In the present study, tea tree essential oil (TTEO) was extracted from Melaleuca alternifolia and was evaluated for its phytochemicals, antifungal, antimicrobial, antidiabetic, and anti-inflammatory activities. GC-FID analysis and fingerprint analysis were performed. Different antioxidant assays were performed like DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2-azinobis-3-ethylbenzothiazoline-6-sulphonic acid), nitric oxide radical, hydroxyl radical, iron-reducing potential, iron chelating activity. Antibacterial activity was observed by the disk diffusion method against gram-positive (G+) and gram-negative (G−) bacteria. Antidiabetic and anti-inflammatory activities were also performed. Antifungal activity against "Aspergillosis" and "Mucormycosis" causing fungal strains was also evaluated. GC-FID revealed the presence of α-terpineol, a major component of TTEO, along with other bioactive components. The IC50 value for various assays was observed in the following order: Hydroxyl radical scavenging activity (7.4486), DPPH (34.0961), ABTS (38.9952), Nitric oxide radical scavenging activity (47.4052). The best antimicrobial activity was against Staphylococcus aureus (MTCC 3160) with an inhibition zone of 0.9 cm. TTEO showed strong anti-inflammatory and antidiabetic potential and can be employed as an antidiabetic agent due to its inhibitory effect on α-amylase activity. Based on these findings, it was concluded that TTEO can be widely employed across various sectors, including aromatherapy, herbal and allopathic medicine, cosmetics, and as a natural biocide, fungicide, and preservative. [ABSTRACT FROM AUTHOR]

In recent times, the healthcare industry has been generating a significant amount of data in distinct formats, such as electronic health records (EHR), clinical trials, genetic data, payments, scientific articles, wearables, and care management databases. Data science is useful for analysis (pattern recognition, hypothesis testing, risk valuation) and prediction. The major, primary usage of data science in the healthcare domain is in medical imaging. At the same time, lung cancer diagnosis has become a hot research topic, as automated disease detection poses numerous benefits. Although numerous approaches have existed in the literature for lung cancer diagnosis, the design of a novel model to automatically identify lung cancer is a challenging task. In this view, this paper designs an automated machine learning (ML) with data science-enabled lung cancer diagnosis and classification (MLDS-LCDC) using computed tomography (CT) images. The presented model initially employs Gaussian filtering (GF)-based pre-processing technique on the CT images collected from the lung cancer database. Besides, they are fed into the normalized cuts (Ncuts) technique where the nodule in the pre-processed image can be determined. Moreover, the oriented FAST and rotated BRIEF (ORB) technique is applied as a feature extractor. At last, sunflower optimization-based wavelet neural network (SFO-WNN) model is employed for the classification of lung cancer. In order to examine the diagnostic outcome of the MLDS-LCDC model, a set of experiments were carried out and the results are investigated in terms of different aspects. The resultant values demonstrated the effectiveness of the MLDS-LCDC model over the other state-of-the-art methods with the maximum sensitivity of 97.01%, specificity of 98.64%, and accuracy of 98.11%. [ABSTRACT FROM AUTHOR]

Aims To perform an integrated comparative analysis of metabolic pathway to understand coenzyme Q10 (CoQ10) production in Agrobacterium tumefaciens. Methods and results Comparative analysis of the CoQ10 metabolic pathway in 10 organisms using a genome to KEGG orthology program (G2KO) and the KEGG database elucidated the completeness of the production pathway in A. tumefaciens. The specific roles of the key precursors and the enzymes in the metabolic network were subsequently confirmed using pathway inhibitors and enhancers. While the use of fosmidomycin and glyphosate was found to inhibit CoQ10 production by 54.54% to 99%, the supplementation of polyprenyl pyrophosphate of the methylerythritol 4-phosphate pathway and 4-hydroxybenzoate precursor of the shikimate pathway did increse the production of CoQ10 by 2.3-fold. Conclusions The present study provides a comprehensive understanding of the CoQ10 biosynthetic pathway in A. tumefaciens , which would assist rational metabolic engineering strategies for augmenting CoQ10 biosynthesis. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is regarded as a neurological disorder well-defined by a specific set of problems associated with social skills, recurrent conduct, and communication. Identifying ASD as soon as possible is favourable due to prior identification of ASD permits prompt interferences in children with ASD. Recognition of ASD related to objective pathogenicmutation screening is the initial step against prior intervention and efficient treatment of children who were affected. Nowadays, healthcare and machine learning (ML) industries are combined for determining the existence of various diseases. This article devises a Jellyfish Search Optimization with Deep Learning Driven ASD Detection and Classification (JSODL-ASDDC) model. The goal of the JSODL-ASDDC algorithm is to identify the different stages of ASD with the help of biomedical data. The proposed JSODLASDDC model initially performs min-max data normalization approach to scale the data into uniform range. In addition, the JSODL-ASDDC model involves JSO based feature selection (JFSO-FS) process to choose optimal feature subsets. Moreover, Gated Recurrent Unit (GRU) based classification model is utilized for the recognition and classification of ASD. Furthermore, the Bacterial Foraging Optimization (BFO) assisted parameter tuning process gets executed to enhance the efficacy of the GRU system. The experimental assessment of the JSODL-ASDDC model is investigated against distinct datasets. The experimental outcomes highlighted the enhanced performances of the JSODL-ASDDC algorithm over recent approaches. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 is biosynthesized by living organisms and considered a medically necessary health constituent thereby drawing the attention of the market. Naturally‐producing microbes are commonly used for the commercial production of coenzyme Q10. The detection of extracted coenzyme Q10 is usually done by high‐performance liquid chromatography and mass spectrometry methods which require sophisticated instrumentation and trained personnel. However, routine quality assessment is required rapidly at multiple steps during the large‐scale production process which necessitates the development of a rapid and relatively easy method for coenzyme Q10 detection. In the present study, a thin‐layer chromatography method is developed for the rapid detection of coenzyme Q10 extracted from the natural producer Agrobacterium tumefaciens. Various mobile phases were screened for the thin‐layer chromatography of coenzyme Q10 and the optimum separation‐detection was observed with methanol and ethyl acetate (8:2, v/v). The same extracted coenzyme Q10 was also analyzed by high‐performance liquid chromatography (the standard method of detection), showing a similar profile as with commercially available standard coenzyme Q10. Furthermore, extract from unstained thin‐layer chromatography spot showed the characteristic spectrum (ultraviolet‐visible) as with standard coenzyme Q10. Conclusively, a simple and inexpensive method for the rapid detection of coenzyme Q10 was developed to aid in the commercial production of this medically important coenzyme. [ABSTRACT FROM AUTHOR]

Palmrosa essential oil (PEO) from Cymbopogon khasianus, is used as complementary and traditional medicine worldwide. The present study aimed at compositional profiling of PEO and molecular docking of PEO bioactive compound geraniol against fungal enzymes chitin synthase (CS), UDP-glycosyltransferase (UDPG) and glucosamine-6-phosphate synthase (GPS), as apposite sites for drug designing against "Aspergillosis" and "Mucormycosis" and in vitro confirmation. Compositional profile of PEO was completed by GC-FID analysis. For molecular docking, Patch-dock tool was conducted. Ligand-enzyme 3D interactions were also calculated. ADMET properties (absorption, distribution, metabolism, excretion and toxicity) were also calculated. GC-FID discovered the occurrence of geraniol as a major component in PEO, thus nominated for docking analysis. Docking analysis specified active binding of geraniol to GPS, CS and UDPG fungal enzymes. Wet-lab authentication was achieved by three fungal strains Aspergillus niger, A. oryzae and Mucor sp. Docking studies revealed that ligand geraniol exhibited intercations with GPS, CS and UDPG fungal enzymes by H-bond and hydrophobic interactions. Geraniol obeyed LIPINSKY rule, and exhibited adequate bioactivity. Wet lab results indicated that PEO was able to inhibit fungal growth against "Aspergillosis" and "Mucormycosis". [ABSTRACT FROM AUTHOR]

In nature, varieties of underutilized fruit-bearing plants are available and have remained underexploited for various reasons. However, the different parts of the plant, mainly the fruit, contributed considerably towards the sustainability of food as abundant sources of imperative phytochemical compounds and possess the potential for revenue generation and the conservation of ecological stability. Ethnobotanical information regarding underutilized plants was acquired from a literature exploration of diverse databases for instance Scopus, Google Scholar, and PubMed up to 2020 from research publications. This review article offers an inclusive summary of about 14 underutilized plants, which are supported through experimental evidence, either in vitro or else in vivo. Bioactive compounds such as the secondary plant metabolites phytochemicals and nutrients available in these underutilized plant parts, such as fruits, leaves, and bark, explain their potential applications in different kinds of industries including mainly those of food and pharmaceutical products. In this sense, the phytonutrient significance, biological activities, or possible mechanistic health-related aspects of these compounds are addressed in this review. Based on the accessible indication on the species' safety and pharmacology, we highlighted diverse ways wherein the therapeutic potential effects against different diseases of underutilized plant parts could be appropriately harnessed for probable incorporation into the country's healthcare structure. This study concluded that cited underutilized plants are an immense source of phytochemicals providing diverse antioxidant and other biological activities, viz: anti-inflammatory, antimicrobial, antioxidant, antidiabetic, chemopreventive, and antiallergic, and hence, they can be exploited as alternative sources of therapeutic bioactive compounds for various pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Cryptanalysis is the process of finding flaws or oversights in an encryption algorithm. Nearly, all encryption algorithms are carefully examined through cryptanalysis to determine the security of the system in which the encryption algorithm has been employed. A5/1 is a well-known encryption algorithm which is inbuilt in mobile phone for securing GSM communication, and therefore, cryptanalysis of this algorithm is also important. A5/1 consists of three linear feedback registers of lengths 23, 22, and 19 bits. Due to the nonlinear clocking mechanism of A5/1, cryptanalytic attacks of guess-and-determine (GD) nature are efficient and more successful. In this paper, we propose a new low keystream GD attack on GSM encryption algorithm A5/1. The basic idea of GD attack is guessing some portion of the registers of A5/1 and determining remaining portion of the registers via the relationship between the register's state and the known intercepted keystream. The guessed and determined register's state is validated by running the cipher forward from that state. If the intercepted keystream matches the generated keystream, we accept it. Otherwise, we discard and try the attack again. The computational complexity and the success rate of the proposed attack are O 2 52 and 96.6%, respectively. [ABSTRACT FROM AUTHOR]

Cymbopogan martinii, also known as Palmarosa, is an underutilized plant of tropical region. Due to outstanding antioxidant potential it has been used as a part of conventional medicine and beauty product. Regardless of its importance, complete pharmacological and phytochemical studies are still in its early stages. In the current study, Palmarosa essential oil (PRO) was extracted from Cymbopogan martinii and was evaluated for its phytochemicals, antimicrobial and antifungal, anti-inflammatory and anti-diabetic and protection from UV rays. Oil from fresh leaves was extracted and analysed for presence of phytochemicals (Tannin, Flavonoids, and Phenolics). Various antioxidant activities like DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2-azinobis-3-ethylbenzothiazoline-6-sulphonic acid), Nitric oxide radical, Hydroxyl radical, iron reducing, iron cheating activity were performed. Antibacterial, anti-inflammatory, Antidiabetic, membrane integrity assay, and UV-absorption assay was also performed. Antifungal activity against "Aspergillosis" and "Mucormycosis" causing fungal strains was also evaluated. High concentration of polyphenolics like Tannin, Flavonoid, phenolics were revealed through phytochemical analysis. GC-FID revealed the presence of Geraniol, major component of Palmarosa oil and other bioactive compound in PRO. PRO showed high anti-inflammatory and anti-diabetic potential and can be used as an Antidiabetic agent due to inhibitory effect on α-amylase activity. Further study revealed that PRO inhibits α-amylase in competitive manner. Hence from the results obtained it is confirmed that the PRO possesses considerable amount of bioactive compounds and can be used in pharmaceutical, food and cosmetic industries. [ABSTRACT FROM AUTHOR]

Cymbopogon martinii, also known as Palmarosa, is an underutilized plant in the tropical region. Due to its outstanding antioxidant potential, it has been used as a part of conventional medicine and beauty product. The objective of the present study was aromatic profiling of Palmarosa essential oil and molecular docking of Palmarosa essential oil bioactive components (Geraniol, Geranial, Linalool, Fenchyl alcohol, 6- methylhept-5-en-2-one, Borneol, Elemol, δ-cadinol) against six bacterial Penicillin)binding Proteins (PBP1a, PBP2a, PBP3, PBP4, PBP5, and PBP 6) and in-vitro support. GC-FID was used to find out aromatic profiling. For docking Cb-dock2 tool was used. Ligand-Protein 3D interactions were also studied. In-silico ADMET pharmacoinformatics aspects (Physicochemical, Lipophilicity, Medicinal Chemistry, Druglikeness, Absorption, Water Solubility, Distribution, Metabolism, Pharmacokinetics, Excretion, Environmental Toxicity, Tox21 Pathway and Toxicophore Rules) with PASS prediction of all the ligands have been bioprospected. Wet lab validation was performed by Gram-positive and Gram-negative bacterial strains. GC-FID profiling revealed the presence of various major and minor components. Docking analysis indicated effective binding of all the ligands with all the six PBPs (PBP1a, PBP2a, PBP3, PBP4, PBP5, and PBP 6). The interaction results indicate that the PBP-Ligand complexes form hydrogen and hydrophobic interactions. in-silico ADMET study revealed that all the ligand molecules have no toxic effect and good absorption as well. Wet lab validation was performed by Gram-positive and Gram-negative bacterial strains. In-vitro results revealed that the Palmarosa oil was able to inhibit the growth of the bacterial strains thus signifying its role as a potent anti-bacterial drug. These ligands can be used as a basic structure, and various structural modifications can ultimately yield stronger molecules. The Palmarosa essential oil could be a promising antibacterial agent against various strains. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is regarded as a neurological disorder well-defined by a specific set of problems associated with social skills, recurrent conduct, and communication. Identifying ASD as soon as possible is favourable due to prior identification of ASD permits prompt interferences in children with ASD. Recognition of ASD related to objective pathogenic mutation screening is the initial step against prior intervention and efficient treatment of children who were affected. Nowadays, healthcare and machine learning (ML) industries are combined for determining the existence of various diseases. This article devises a Jellyfish Search Optimization with Deep Learning Driven ASD Detection and Classification (JSODL-ASDDC) model. The goal of the JSODL-ASDDC algorithm is to identify the different stages of ASD with the help of biomedical data. The proposed JSODLASDDC model initially performs min-max data normalization approach to scale the data into uniform range. In addition, the JSODL-ASDDC model involves JSO based feature selection (JFSO-FS) process to choose optimal feature subsets. Moreover, Gated Recurrent Unit (GRU) based classification model is utilized for the recognition and classification of ASD. Furthermore, the Bacterial Foraging Optimization (BFO) assisted parameter tuning process gets executed to enhance the efficacy of the GRU system. The experimental assessment of the JSODL-ASDDC model is investigated against distinct datasets. The experimental outcomes highlighted the enhanced performances of the JSODL-ASDDC algorithm over recent approaches. [ABSTRACT FROM AUTHOR]

In present times, a massive quantity of big data has been generated by the Internet of Things (IoT) devices for a wide range of applications. The IoT devices generate an enormous data quantity that is troublesome for data processing and analytics functionalities, which is effortlessly managed by the cloud before the explosive development of the IoT. Specifically, the big IoT data analytics by mobile edge computing (MEC) becomes a hot research topic and needs comprehensive research works for intelligent decision making. This paper introduces a new generative adversarial network (GAN) with a quantum elephant herd optimization (QEHO) algorithm for MEC in IoT enabled big data environment called GAN-QEHO. The presented GAN-QEHO algorithm follows two-stage processes, namely feature selection (FS) and data classification. The QEHO algorithm is used to elect an optimal feature subset for the FS process. By the quantization of elephant individuals, the search scope of feature space can be enhanced, and an optimal tradeoff has been attained among exploration and exploitation. Then, the GAN model is employed for the classification process to identify different class labels. In order to validate the experimental results analysis of the GAN-QEHO algorithm, a series of simulations take place in terms of diverse aspects. [ABSTRACT FROM AUTHOR]

Purpose: Businesses need to make quick decisions and adjustments to fulfill the growing online demand. Previous studies examined various factors affecting the online sales performance of products such as books, electronics and movies; however, they paid limited attention toward the local brand clothing products. The current study investigates the importance of different kinds of seller-generated and consumer-generated signals such as price, discount, product ratings, review volume, review sentiment, number of questions and interaction between some of these factors for predicting the sales performance of clothing products. Design/methodology/approach: The multiple linear regressions has been employed to investigate the influence of various predictor variables on sales performance. The study also examines the importance of these predictor variables by using different machine learning models, including random forest (RF), neural networks and support vector regression (SVR). Findings: The findings of the study emphasize the importance of price and discount rates offered on the product. The quantitative characteristics of reviews, such as review volume and average rating, have been found to be more important predictors than sentiment strengths. However, the sentiment strength of reviews with higher helpfulness scores plays a significant role in predicting sales performance. Originality/value: The study highlights the varying importance of seller-based and consumer-based signals in predicting sales performance. It also investigates the interaction effect of these two kinds of signals. The consumer-generated signals have been further divided into two components based on social influence theory, and the interaction effects of these components have also been examined. [ABSTRACT FROM AUTHOR]

Hemoglobin degradation is crucial for the growth and survival of Plasmodium falciparum in human erythrocytes. Although the process of Hb degradation has been studied in detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein (PfHDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of PfHDP‐GFP fusion protein from a transgenic line using GFP trap beads showed the association of PfHDP with Hb as well as with the members of PTEX translocon complex. Association of PfHDP with Hb or Pfexp‐2, a component of translocon complex was confirmed by protein–protein interaction and immunolocalization tools. Based on these associations, we studied the role of PfHDP in Hb uptake using the PfHDP‐HA‐GlmS transgenic parasites line. PfHDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild‐type parasites. Morphological analysis of PfHDP‐HA‐GlmS transgenic parasites in the presence of GlcN showed food vacuole abnormalities and parasite stress, thereby causing a growth defect in the development of these parasites. Transient knockdown of a member of translocon complex, PfHSP101 in HSP101‐DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between PfHDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for PfHDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of PfHDP, making it an extremely important target for developing new antimalarials. [ABSTRACT FROM AUTHOR]

India has made significant progress in improving maternal and child health. However, there are persistent disparities in maternal and child morbidity and mortality in many communities. Mistreatment of women in childbirth and gender-based violence are common and reduce women's sense of safety. Recently, the Government of India committed to establishing a specialized midwifery cadre: Nurse Practitioners in Midwifery (NPMs). Integration of NPMs into the current health system has the potential to increase respectful maternity care, reduce unnecessary interventions, and improve resource allocation, ultimately improving maternal-newborn outcomes. To synthesize the evidence on effective midwifery integration, we conducted a desk review of peer-reviewed articles, reports and regulatory documents describing models of practice, organization of health services and lessons learned from other countries. We also interviewed key informants in India who described the current state of the healthcare system, opportunities, and anticipated challenges to establishing a new cadre of midwives. Using an intersectional feminist theoretical framework, we triangulated the findings from the desk review with interview data to identify levers for change and recommendations. Findings from the desk review highlight that benefits of midwifery on outcomes and experience link to models of midwifery care, and limited scope of practice and prohibitive practice settings are threats to successful integration. Interviews with key informants affirm the importance of meeting global standards for practice, education, inter-professional collaboration and midwifery leadership. Key informants noted that the expansion of respectful maternity care and improved outcomes will depend on the scope and model of practice for the cadre. Domains needing attention include building professional identity; creating a robust, sustainable education system; addressing existing inter-professional issues and strengthening referral and quality monitoring systems. Public and professional education on midwifery roles and scope of practice, improved regulatory conditions and enabling practice environments will be key to successful integration of midwives in India. [ABSTRACT FROM AUTHOR]

In the last decade, a diverse array of information systems (IS) has emerged to help organisations achieve their performance goals. As a result, global spending on information technology (IT) has increased manifold. These developments have reopened the fundamental question of how IS success is shaped at the organisational level. Scholars and practitioners would also like to understand if, compared to the individual level, IS success patterns differ at the organisational level. The last meta-analysis of IS success was conducted nearly a decade ago and it could not examine IS success at the organisational level. There is also a need to gain a deeper understanding of key contingencies influencing success at the organisational level. Based on a comprehensive meta-analysis of research studies conducted in the last decade, we not only report how IS success patterns are shaped at the organisational level but also show how these patterns compare to success configurations at the individual level. Additionally, we conduct detailed multi-level meta-analyses of system complexity and user type as two key contingencies influencing success at both individual as well as organisational levels. Findings of our moderation analyses reveal distinct constructions of IS success across both levels. [ABSTRACT FROM AUTHOR]

Essential oil from Cymbopogon pendulus is immensely useful in various sectors like food, pharmaceutical, and cosmetic industries. Since this oil is hydrophobic, unstable, and volatile, hence encapsulation by using nanoemulsions technology is the best way to protect it. This study reports biosynthesis of O/W (oil/water) nanoemulsions based on essential oil from Cymbopogon pendulus and analysis of its biological activities. O/W nanoemulsions were prepared by using tween 20/80, sodium dodecyl sulphate as surfactants, and ethanol as co-surfactants. Fingerprinting of nanoemulsions using UV, fluorescent, and FT-IR was studied along with other parameters like pH and conductivity. Biological activities like antibacterial, anti-inflammatory, and anti-diabetic activities and drug release pharmokinetics were evaluated. Ethanol containing nanoemulsions was noticeably smaller than other nanoemulsions. Encapsulation efficiency of nanoemulsions was in the range from 41 to 60%. Nanoemulsions were spherical in shape and stable even after 50 days of storage. Appreciable biological activities like anti-bacterial, anti-inflammatory, and anti-diabetic activities were detected. Drug kinetic study revealed that nanoemulsions exhibited Korsmeyer-Peppas model. Based on this, the possible role of lemon grass oil-based nanoemulsions in cosmetic, food, and pharma sectors has been discussed. [ABSTRACT FROM AUTHOR]

This is the era of Intelligent Cognitive Radio Network (CRN) technology that provides the available spectrum with efficient utilization. Cognitive Radio (CR) technology must promise to allow interference-free spectrum access by users. The paper discusses the several attacks and motives of attacks. The authentication mechanism role to prevent the attacks for hassle-free spectrum utilization is demonstrated. In this paper, resolving the cognitive network security issues by the authentication mechanism and the methods and need of authentication is discussed. This paper addresses the research challenges in the way of securing the CRN and countermeasures in CRN security strategies. Spectrum sensing data falsification (SSDF) attack is most disruptive in which the malicious users degrade the decision-making process by sending the false sensing reports to data fusion center's thus preventing honest users from utilizing the spectrum. In this paper, to counter the SSDF attack, the trust-based security mechanism is demonstrated to authenticate the honest users and it is observed that the proposed framework in the MATLAB environment is efficient and able to detect malicious users. CR technology is the strategy applied to the spectrum to make it efficient for wireless communication. The strategy is an intelligent way to access the spectrum as it can learn its environment and make decisions by easy adaptation of operating parameters. The initial step is to sense the spectrum available further steps are spectrum decision making, spectrum management, and spectrum mobility. The network is vulnerable to various attacks on spectrum sensing and policy protocols which lead to disturbing functionality of CR technology. The defence mechanism based on public-key cryptography is proposed in which the Primary User (PU) is authenticated by appending signature provided to PU signal. Authentication with a tag to the primary users is another perspective proposed. CRN technology should provide integrity, confidentiality and authenticity to the users. [ABSTRACT FROM AUTHOR]

Ocimum spp. are the widely studied herbal plants because of their diverse biological activities. The present study aimed at comparative extraction of secondary metabolites and evaluation of their biological activities in different solvents such as acetone, ethanol, methanol, and water. Three Ocimum species, namely Ocimum basilicum L. (Green tulsi), Ocimum gratissimum L. (Jungli tulsi), and Ocimum tenuiflorum (Black tulsi), were selected for this study. Leaf extracts from dried powder of these species were prepared in different solvents. The contents of total phenolics, flavonoids, and total condensed tannins were estimated using standard assays. Fingerprint analysis using UV, Fourier transform infrared (FT-IR), and fluorescent spectroscopy was also conducted. Total antioxidant, antidiabetic, and anti-inflammatory activities of the extracts were evaluated. Fingerprint analysis indicated the presence of a sufficient level of polyphenolics in all the solvent extracts. Among all the solvents, acetone provided a higher yield of phenolics, flavonoids, and tannins in all Ocimum species. Black Ocimum showed the maximum level of antioxidants. All Ocimum extracts exhibited a sufficient level of antidiabetic and anti-inflammatory activities. The results indicated that by using appropriate solvents, bioactive compounds from Ocimum species can be extracted and used as therapeutic agents with potential biological activities. [ABSTRACT FROM AUTHOR]

Cymbopogon pendulus, also known as lemon grass, is an underutilized plant of tropical and subtropical regions. Owing to its antioxidant values, it has been used as folk medicine, and folk cosmetic. Despite its importance, detailed phytochemical and pharmacological studies remain infancy. In the present study, lemon grass essential oil (LGO) was extracted from Cymbopogon pendulus and was analysed for its phytochemical, in-vitro antioxidant, antimicrobial and antifungal, anti-inflammatory and anti-diabetic and insecticidal properties. Essential oil from fresh leaves was isolated and phytochemical analysis (phenolics, flavonoids and tannins) was studied. Different antioxidant activities like DPPH (1,1-diphenyl-2-picrylhydrazyl), iron-reducing power, iron chelating power and hydroxyl scavenging activities were also studied. Anti-inflammatory, anti-diabetic, anti-fungal and anti-microbial potential of LGO was evaluated. GC-FID was used to identify bioactives. The phytochemical analysis of LGO revealed high concentrations of polyphenolics that is phenols, flavonoids, and tannin contents. GC-FID revealed the presence of citral and other bioactive molecules in LGO. LGO showed high potential as anti-inflammatory, anti-fungal and anti-microbial agent. LGO showed high potential to be used as anti-diabetic agent due to its high inhibitory effect on alpha-amylase activity. Further kinetic studies revealed competitive inhibition of α-amylase by LGO. LGO exhibited strong Insecticidal potential against weevil (Callosobruchus) commonly found in stored grains. The results obtained confirmed the information that LGO possesses significant bioactive components advantageous for pharma, food and cosmetic industries. [ABSTRACT FROM AUTHOR]

Background: Aspergillosis, has recently confounded some states of India. Due to major role in fungal cell wall synthesis, in the present study UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase were chosen as an appropriate sites to design drug. The objective of present study was molecular docking of lemon grass essential oil component citral and in vitro validation. GC-FID analysis was used to find out aromatic profile. For docking, Patch-dock analysis was used. Ligand Protein 2D and 3D Interactions were also studied. Drug likeliness, and toxicity profile were also studied. Docking analysis indicated effective binding of citral to UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase. In vitro validation was performed by fungal strain Aspergillus fumigatum. Results: GC-FID profiling revealed the presence of citral as major bioactive compound. Interactions results indicated that, UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase enzymes and citral complexes forms hydrogen and hydrophobic interactions. Citral also depicted drug likeliness by LIPINSKY rule, sufficient level of bioactivity, drug likeliness and toxicity. Conclusion: In vitro results revealed that lemon grass oil was able to inhibit growth of fungal strains toxicity thus signifying its role as potent anti-fungal drug. [ABSTRACT FROM AUTHOR]

Background: Lantana camara, Parthenium hysterophorus, Ageratum conyzoidus and Ricinus communis are underutilized plants. These plants are traditionally used in many health related areas. The context and purpose of the study: To investigate the photochemicals present in underutilized plants Lantana camara, Parthenium hysterophorus, Ageratum conyzoidus and Ricinus communis: Methods: Qualitative, quantitative screening, compound identification by UV-VIS method and Fluorescent spectroscopy and FT-IR based identification of functional groups of active chemical components were studied. Organic solvents leave extracts (ethanol, methanol, acetone) were tested for availability of secondary metabolites. Results, the main findings: UV-VIS spectrum showed different peaks with different absorption in all plants. The method of quantitative analysis in UV-VIS spectrum was proved in terms of linearity, LOD and LOQ AND various secondary metabolites were detected in the plant extracts. Florescent analysis confirmed the presence of secondary metabolites like alkaloids and phenolics. The FT-IR spectrum values indicated the presence of C-H stretching, O-H bending, C-C stretching and confirmed the presence of alcohols, phenols, alkanes and amines in acetone extracts. Conclusion: The results confirmed the fact that these plants poses important bioactive components useful for human mankind, so further investigation may needed. [ABSTRACT FROM AUTHOR]

Ocimum spp., also known as "tulsi" member of Lamiaceae, are widely studied herbal plants. Due to their diverse biological activities, Ocimum basils are the most popular traditional herbal remedies against various diseases. The aim of the present study is comparative chemical composition profiling of bioactive compounds from three species viz: Ocimum tenuiflorum (Black tulsi), Ocimum gratissimum (Jungli tulsi), and Ocimum basilicum (Green tulsi). Leaves extracts from dried powder were prepared in acetone/water mixture solvent. GC-FID was used to study the comparative chemical profile of cultivars. The results revealed the presence of various bioactive constituents in acetone extracts but in a species-dependent manner. The main bioactive constituents in O. tenuiflorum were: ß-bisabolene and tetracontane, in O. gratissimum were: 4-methyl - 2 -pentyl acetate and tetracontane, in O. basilicum were: ß-bisabolene and tetracontane. The results indicated that bioactive compounds from tulsi species can be extracted and used as therapeutic agents having potential biological activities. [ABSTRACT FROM AUTHOR]

Netnography has emerged as the dominant social media research that allows researchers to understand and assimilate available knowledge for practical insights. However, limited awareness inhibits its development. This systematic literature review attempts to understand the evolution of netnography under the research domain to promote its usage and determine future research directions. The study revealed four broad clusters of the literature based on their prevalence: consumer experience and behaviour, phenomena and events, social media, and digital government. The study also highlights the limited development of new-age phenomena such as brand hate, cyber tourism, and special interest tourism. The study contributes to the domain of netnography in two ways: first by providing a thematic classification of the studies conducted in the decade of 2009-21 and second by suggesting potential future research directions, including scientific inquiry on the new-age phenomena blooming due to high internet penetration. [ABSTRACT FROM AUTHOR]

Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2gib005Δ8/+) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability. Synopsis: Protein kinase C beta (PRKCB) promotes vascular permeability, and its hyper‐activation has been linked to diabetic retinopathy. Here, the novel, evolutionarily conserved lncRNA VEAL2 is shown to inhibit PRKCB activity and junctional permeability in zebrafish and in human vascular endothelium. VEAL2 inhibits vascular permeability and modulates junctional assembly in zebrafish vasculature and in human endothelial cells.VEAL2 inhibits PRKCB activity by competing with diacylglycerol binding to its C1 domain.The levels of VEAL2 are reduced in retinal choroid tissue of patients with diabetic retinopathy.Ectopic expression of VEAL2 ameliorates the hyperglycemic disease pathophysiology in human endothelial cells. [ABSTRACT FROM AUTHOR]

The human malaria parasite, Plasmodium falciparum possesses unique gliding machinery referred to as the glideosome that powers its entry into the insect and vertebrate hosts. Several parasite proteins including Photosensitized INA-labelled protein 1 (PhIL1) have been shown to associate with glideosome machinery. Here we describe a novel PhIL1 associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of the merozoite. Using an experimental genetics approach, we characterized the role(s) of three proteins associated with PhIL1: a glideosome associated protein- PfGAPM2, an IMC structural protein- PfALV5, and an uncharacterized protein—referred here as PfPhIP (PhIL1 Interacting Protein). Parasites lacking PfPhIP or PfGAPM2 were unable to invade host RBCs. Additionally, the downregulation of PfPhIP resulted in significant defects in merozoite segmentation. Furthermore, the PfPhIP and PfGAPM2 depleted parasites showed abrogation of reorientation/gliding. However, initial attachment with host RBCs was not affected in these parasites. Together, the data presented here show that proteins of the PhIL1-associated complex play an important role in the orientation of P. falciparum merozoites following initial attachment, which is crucial for the formation of a tight junction and hence invasion of host erythrocytes. Author summary: Invasion of Plasmodium merozoites into RBCs is a multistep process that involves initial attachment of merozoites to the RBC surface, their reorientation, and subsequent gliding into RBCs using glideosome machinery. The glideosome machinery lies between the plasma membrane and inner membrane complex (IMC) and consists of MyoA, its interacting protein; MTIP, gliding associated proteins (GAPs), and a Photosensitized INA labeled protein (PhIL1)-associated protein complex. Here, we demonstrate that the deletion of any of two components of the PhIL1-associated complex, PfPhIP or PfGAPM2, aborts merozoite reorientation and blocks their invasion into RBCs. The study thus provides new molecular and mechanistic insights into merozoite invasion of RBCs. [ABSTRACT FROM AUTHOR]

SARS-Cov-2, responsible for COVID-19, is caused by RNA-based coronavirus. Recently 2nd wave of COVID-19 has devastated the pandemic worldwide. Inhibitors of glycolysis pathways have been evaluated to curtail the SARS-CoV-2 infectivity and spread in the host cells, but still at an infancy stage. Due to its key role in glycolysis, in the present study hexokinase has been cited as a key target for therapeutic drug synthesis. Molecular docking and pharmacological study of 1-8 cineole bioactive from eucalyptus essential oil were designed against hexokinase enzyme. Patch-dock analysis was used for docking. Ligand Protein 2D and 3D Interactions were also studied. Drug likes and toxicity profile was also evaluated. Cancer cell line toxicity profile was also studied. Molecular docking illustrated the perfect binding of 1-8 cineole to hexokinase protein. 2D and 3D studies revealed that hexokinase enzyme exhibited hydrogen and hydrophobic interactions with 1-8 cineole. 1-8 cineole also depicted a sufficient level of cancer cell line toxicity. Drug likeliness profiles studies provided guidelines and mechanistic scope for the identification of 1-8 cineole as a potent anti-COVID 19 drug. Therefore, it was concluded that 1-8 cineole from eucalyptus essential oil poses the therapeutic potential to combat infection of SARS-Cov-19. [ABSTRACT FROM AUTHOR]

Black fungus also known as Mucormycosis, has recently devastated some states of India. It has been declared pandemic now. Inhibitors of glucon synthesis pathways have been evaluated to curtail the Mucormycosis but still at infancy stage. Due to key role in glucon synthesis, in the present study β -glucan synthase has been regarded as a suitable target for drug design. In-silico docking and pharmacological study was designed to evaluate the effect of potent bioactive molecule 1-8 cineole present in essential oils of eucalyptus plant leaves against β -glucan synthase enzyme. Till date there is no work is undertaken on insilico analysis of this compound against β -glucan synthase. Patch-dock analysis was used for docking. Ligand Protein 2D and 3D Interactions were also studied. Drug likes and toxicity profile was also evaluated. Cancer cell line toxicity profile was also studied. The calculated parameters such as docking score indicated effective binding of 1-8 cineole to β - glucan synthase -protein. Interactions results indicated that, β -glucan synthase enzyme and 1-8 cineole complexes forms hydrogen and hydrophobic interactions. 1-8 cineole also depicted sufficient level of cancer cell line toxicity. Drug likeliness profiles by assaying absorption, distribution, metabolism, excretion and toxicity (ADMET) studies provided guidelines and mechanistic scope for identification of 1-8 cineole as potent anti-fungal drug. Therefore, essential oil from eucalyptus may represent potential herbal treatment to act as anti-fungal drug. [ABSTRACT FROM AUTHOR]

Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin's expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management. [ABSTRACT FROM AUTHOR]

Traboulsi syndrome is a rare autosomal recessive genetic disorder. The present study aimed to identify the pathogenic variants in the ASPH gene responsible for a rare and unique presentation of Traboulsi syndrome associated with cardiac disorder. DNA was isolated from the blood samples from 3 clinically diagnosed Traboulsi syndrome patients (n = 3) after obtaining a prior-informed consent. All three had classical ocular and facial dysmorphic features, and two of them also had associated cardiac problems. Mutation screening was performed for the exons of ASPH gene by Sanger sequencing in these patients and 350 controls. Sequence data analysis was performed using Seqscape and insilico protein analysis by SIFT, PyMOL, and Dynamut softwares. A novel homozygous variant(c.1853 T > A) in exon 21 was identified by Sanger sequencing in two of the three cases while a known pathogenic variant in exon 25 was identified in the third proband. The novel nonsense variant in exon 21 results in a premature truncation of gene resulting in a protein of 543 amino acids. This variant is not reported in ExAC, dbSNP and 1000 genome databases. Both the patients harboring this novel variant, had a unique presentation of Traboulsi syndrome with cardiac dysfunction. In silico analysis predicted the mutation to affect the calcium-binding activity of the gene which might explain the associated cardiac dysfunction in these two patients. The novel pathogenic mutation displayed a perfect genotype-phenotype correlation in two probands of Traboulsi syndrome with cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Helicobacter pylori , a type 1 carcinogen, accounts for numerous gastric cancer-related deaths worldwide. Repurposing existing drugs or developing new ones for a combinatorial approach against increasing antimicrobial resistance is the need of the hour. This study highlights the efficacy of acriflavine hydrochloride (ACF-HCl) in inhibiting the growth of H. pylori reference strain and antibiotic-resistant clinical isolates at low concentrations. ACF-HCl inhibits H. pylori growth at MIC value 10 times less than that in Escherichia coli , another Gram-negative bacteria. Furthermore, ACF-HCl demonstrates synergistic effect with clarithromycin, a commonly used antibiotic against H. pylori. ACF-HCl treatment also eradicates H. pylori infection in the mice model efficiently. Our in vitro data indicate that bacterial membrane is the prime target. The novel action of ACF-HCl against antibiotic-resistant clinical isolates, synergistic effect with the conventional antibiotic clarithromycin and eradication of H. pylori from infected mice highlight the potential of ACF-HCl as a promising therapeutic agent against H. pylori by itself as well as for combinatorial therapy. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is the most common etiology of fungal endophthalmitis in India, while Candida albicans is the causative agent in the West. In this study, we determined the role of microglial cells in evoking an inflammatory response following an infection with A. flavus and C. albicans strains isolated from patients with endophthalmitis. Microglia (CHME-3) cells were infected with A. flavus and C. albicans and the expression of Toll-Like Receptors (TLRs), cytokines and Matrix metalloproteinases (MMPs) were assessed at various time intervals. A. flavus infected cells induced higher expressions of TLR-1, -2, -5, -6, -7 and -9 and cytokines such as IL-1α, IL-6, IL-8, IL-10 and IL-17. In contrast, C. albicans infected microglia induced only TLR-2 along with the downregulation of IL-10 and IL-17. The expression of MMP-9 (Matrix metalloproteinase-9) was however upregulated in both A. flavus and C. albicans infected microglia. These results indicate that microglial cells have the ability to incite an innate response towards endophthalmitis causing fungal pathogens via TLRs and inflammatory mediators. Moreover, our study highlights the differential responses of microglia towards yeast vs. filamentous fungi. [ABSTRACT FROM AUTHOR]