Cholestatic Liver Disease due to Novel USP53 Mutations: A Case Series of Three Indian Children.

Cholestatic liver diseases in children often have an underlying genetic defect. Genetic testing by next-generation sequencing has become a crucial part of the diagnostic armamentarium in such clinical scenarios. Here, we report three children who presented with early-onset cholestatic jaundice and pruritus. All of them had low gamma-glutamyl transferase and high serum bile acid levels. Symptoms were alleviated with ursodeoxycholic acid and cholestyramine in all 3 children with normal LFT at follow-up. They were detected to have novel pathogenic USP53 mutations (2 homozygous, 1 compound heterozygous) on next-generation sequencing which have previously not been reported.

siRNA therapeutics: insights, challenges, remedies and future prospects.

INTRODUCTION: Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action. AREAS COVERED: The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities. EXPERT OPINION: The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications.

Drug permeation enhancement, efficacy, and safety assessment of azelaic acid loaded SNEDDS hydrogel to overcome the treatment barriers of atopic dermatitis.

Atopic dermatitis is one of the most widespread chronic inflammatory skin conditions that can occur at any age, though the prevalence is highest in children. The purpose of the current study was to prepare and optimize the azelaic acid (AzA) loaded SNEDDS using Pseudo ternary phase diagram, which was subsequently incorporated into the Carbopol 940 hydrogel for the treatment of atopic dermatitis. The composition was evaluated for size, entrapment efficiency, in vitro, ex vivo, and in vivo studies. The polydispersity index of the optimized preparation was found to be less than 0.5, and the size of the distributed globules was found to be 151.20 ± 3.67 nm. The SNEDDS hydrogel was characterized for pH, viscosity, spreadability, and texture analysis. When compared to the marketed formulation, SNEDDS hydrogel was found to have a higher rate of permeation through the rat skin. In addition, a skin irritation test carried out on experimental animals showed that the SNEDDS formulation did not exhibit any erythematous symptoms after a 24-h exposure. In conclusion, the topical delivery of AzA through the skin using SNEDDS hydrogel could prove to be an effective approach for the treatment of atopic dermatitis.

Nanocrystals as an emerging nanocarrier for the management of dermatological diseases.

Skin conditions are amongst the most prevalent health issues in the world and come with a heavy economic, social, and psychological burden. Incurable and chronic skin conditions like eczema, psoriasis, fungal infections are linked to major morbidity in the manner of physical pain and a reduction in quality life of patients. Several drugs have difficulties for penetrating the skin due to the barrier mechanism of the skin layers and the incompatible physicochemical characteristics of the drugs. This has led to the introduction of innovative drug delivery methods. Currently, formulations depend on nanocrystals have indeed been researched for topical administration of drugs and have resulted in enhanced skin penetration. This review focuses on skin penetration barriers, modern methods to enhance topical distribution, and the use of nanocrystals to overcome these barriers. By means of mechanisms such as adherence to skin, creation of diffusional corona, targeting of hair follicles, and the generation of a greater concentration gradient throughout the skin, nanocrystals could enhance transport across the skin. Scientists working on product formulations incorporating chemicals that are "challenging-to-deliver" topically may find the most current findings to be of relevance.

Wetland health assessment using DPSI framework: a case study in Kolkata Metropolitan Area.

Wetlands are among the most valuable components of the ecosystem, playing an important role in preventing floods, maintaining the hydrological cycle, protecting against natural hazards, and controlling local weather conditions and ecological restoration. The Kolkata Metropolitan Area (KMA) is considered one of the most ecologically valuable regions in terms of wetland ecosystem, but due to haphazard development and human activities, the wetlands of the city are under constant threat of degradation. Therefore, this study aims to assess the factors responsible for wetland health and their dynamics using Driving Force-Pressure-State-Impact (DPSI) framework. To assess wetland health during 2011-2020, seventeen indicators and four sub-indicators were selected to calculate weights using the analytic hierarchy process (AHP). The results showed that most of the municipalities in the healthy category were in the pressure (P) section in 2011, while fluctuations were observed in the impact (I) section in several wards during 2011-20. The condition section (S) showed the overall change in the water, vegetation, and built-up categories from 2011 to 2020, so the most dominant category was "healthy," followed by "unhealthy" and "poor." The highly significant factors worsening wetland health were population density (B1), road density (B3), per capita wastewater generation (B5), per capita solid waste generation (B7), biological oxygen demand (D1a), dissolved oxygen (D1b), pH (D1c), and total coliform (D1d). The results of the study can help develop sustainable conservation and management of the wetland ecosystem in the KMA urban area and at the global level with similar geographical conditions.

Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer.

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.

Monitoring built-up area expansion led by industrial transformation in Delhi using geospatial techniques.

Historically, industrialization has been a catalyst for built-up expansion generated by economic growth that transforms a landscape. In India, there is a paucity of exploration into how the economic shift transforms the cityscape. Therefore, the objective of current research work was to monitor built-up growth induced by industrialization using Landsat datasets and registered industry data. The k-means clustering technique was applied for assessing land use/land cover, Shannon entropy for sprawl, and Pearson for correlation between industrial growth and built-up expansion. The results manifest exponential trend in industrialization with 102-year registered industry record along with increase in built-up density from 0.30 in 1989 to 0.69 by 2019 and in the entire Delhi; it rose from 0.16 to 0.39. Furthermore, Shannon entropy confirmed the sprawl and the strong positive correlation was found among built-up of industrial areas and built-up of Delhi and registered industries. The striking chorological change in industrial as well as city's landscape was observed co-occurring with the dynamics of economic reforms. The outcome of current research could be utilized for the sustainable planning of industrial landscape in Delhi and cities with alike geographical conditions.

Recent advances in microbeads-based drug delivery system for achieving controlled drug release.

Novel drug delivery system endows a beneficial method for achieving a desired drug concentration at the appropriate site in the body. The concept of targeted drug delivery has been emerged to localize the drug in the targeted tissue of interest while reducing the relative concentration of the medication in the surrounding tissues. This could be easily accomplished by using different multi-particulate dosage forms like pellets, granules, microcapsules, liposomes, beads. But the major drawbacks associated with them are the use of harsh chemicals and an elevated temperature for their preparation. Preparation of microbeads by ionotropic gelation and emulsion gelation method overcomes these problems by neither using harsh chemicals nor elevated temperature for their preparation. Thus, this can be proved to be a better alternative over other dosage forms. Several parameters were studied in terms of their morphology, particle size, encapsulation efficiency, swelling ratio, mucoadhesivity, etc. The endeavor of present article is toward presenting a wider perspective of the comprehensive knowledge available in the field of microbeads. Thus, the intent of this review is to recapitulate the relevance of microbeads.

Polymeric nanoparticles-siRNA as an emerging nano-polyplexes against ovarian cancer.

Ovarian cancer (OC) is considered fifth-deadliest cancer globally responsible for high mortality in women. As the conventional therapeutic and diagnostic approaches are ineffective in increasing the survival rates of advanced staged patients by more than 5 years, OC has resulted in high morbidity and mortality rates over the last two decades. As a result, there is a dire need for innovative treatment approaches to address the issues. RNAi and nanotechnology can be considered the most appropriate strategies that can be used to improve OC therapy and help circumvent the chemo-resistance. siRNA is considered highly successful in facilitating the knockdown of specific genes on entering the cytosol when administered in-vivo via inhibiting the mRNA expression responsible for translation of those specific genes through the mechanism called RNA interference (RNAi). However, the primary barrier of utmost importance in the clinical efficacy of employed siRNA for the treatment of OC is the systemic distribution to the targeted site from the administration site. As a result, nanoparticles are constructed to carry the siRNA molecules inside them to the targeted site by preventing serum degradation and enhancing the serum stability of administered siRNA. The present review assesses the developments made in the polymeric-based nanoparticle siRNA delivery for targeting particular genes involved in the prognosis of ovarian cancers and surpassing the chemo-resistance and thus improving the therapeutic potentials of administered agents.

Blood Acylated Ghrelin Concentrations in Healthy Term Newborns: A Prospective Cohort Study.

OBJECTIVE: The effect of ghrelin, a growth hormone (GH) secretagogue on growth of neonates, has been studied in the past, but not fully clarified. We aimed to investigate the relationship between ghrelin and growth parameters at birth and at the age of three months in healthy term infants. Methodology. This was a prospective observational study carried out in a tertiary care hospital. Eighty-four infants born at gestational ages between 37 and 42 weeks and classified as term small for gestational age (SGA) and appropriate for gestational age (AGA) were included in the study. Estimation of acylated ghrelin (AG) concentrations was done in the cord blood at birth and in venous blood at the age of 3 months in all the infants. The correlation between AG concentrations and growth parameters at birth and at 3 months was studied. RESULTS: AG concentrations were significantly higher in SGA (236.16 ± 152.4 pg/ml) than AGA neonates (59.45 ± 20.95 pg/ml) at birth. Concentrations were observed to be negatively correlated with birth weight (r = -0.34, p value 0.03), birth length, and head circumference (r = -0.509 and -0.376, respectively) in SGA neonates. However, at 3 months, AG concentrations did not correlate with changes in anthropometric parameters in both the groups. CONCLUSION: Cord acylated ghrelin concentrations are higher in SGA neonates, and the concentrations are inversely proportional to the birth weight. Hence, its role as a surrogate marker for intrauterine nutrition can be suggested. However, its concentrations do not correlate with anthropometric parameters in early postnatal growth, suggesting it may not have a direct role in postnatal growth.