Musculocontractural type of Ehlers-Danlos syndrome with novel CHST14 pathogenic variant in two siblings.

Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing.

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol.

In the current work, we analyzed the origin of difference in stabilities among the germacrene A and hedycaryol-derived carbocations. This study focused on twelve hydrocarbons derived from germacrene A and twelve from hedycaryol, which can be divided into three groups: four molecules containing 6-6 bicyclic rings, four 5-7 bicyclic compounds with the carbocation being on the seven-membered ring and the remaining four 5-7 bicyclic compounds with the carbocation on the five-membered ring. The variations in energy within the groups of carbocations (i.e., 6-6 and two kinds of 5-7 bicyclic carbocations) can be ascribed to intramolecular repulsion interactions, as seen from non-covalent interactions plots. Despite the structural similarities between germacrene A and hedycaryol cations, they possess a somewhat different stability trend. These differences are attributed to C+···OH intramolecular interactions present in some hedycaryol cations, which are absent in the carbocations derived from germecrene A.

Design and development of 3D printed shape memory triphasic polymer-ceramic bioactive scaffolds for bone tissue engineering.

Scaffolds for bone tissue engineering require considerable mechanical strength to repair damaged bone defects. In this study, we designed and developed mechanically competent composite shape memory triphasic bone scaffolds using fused filament fabrication (FFF) three dimensional (3D) printing. Wollastonite particles (WP) were incorporated into the poly lactic acid (PLA)/polycaprolactone (PCL) matrix as a reinforcing agent (up to 40 wt%) to harness osteoconductive and load-bearing properties from the 3D printed scaffolds. PCL as a minor phase (20 wt%) was added to enhance the toughening effect and induce the shape memory effect in the triphasic composite scaffolds. The 3D-printed composite scaffolds were studied for morphological, thermal, and mechanical properties, in vitro degradation, biocompatibility, and shape memory behaviour. The composite scaffold had interconnected pores of 550 µm, porosity of more than 50%, and appreciable compressive strength (∼50 MPa), which was over 90% greater than that of the pristine PLA scaffolds. The flexural strength was improved by 140% for 40 wt% of WP loading. The inclusion of WP did not affect the thermal property of the scaffolds; however, the inclusion of PCL reduced the thermal stability. An accelerated in vitro degradation was observed for WP incorporated composite scaffolds compared to pristine PLA scaffolds. The inclusion of WP improved the hydrophilic property of the scaffolds, and the result was significant for 40 wt% WP incorporated composite scaffolds having a water contact angle of 49.61°. The triphasic scaffold exhibited excellent shape recovery properties with a shape recovery ratio of ∼84%. These scaffolds were studied for their protein adsorption, cell proliferation, and bone mineralization potential. The incorporation of WP reduced the protein adsorption capacity of the composite scaffolds. The scaffold did not leach any toxic substance and demonstrated good cell viability, indicating its biocompatibility and growth-promoting behavior. The osteogenic potential of the WP incorporated scaffolds was observed in MC3T3-E1 cells, revealing early mineralization in pre-osteoblast cells cultured in different WP incorporated composite scaffolds. These results suggest that 3D-printed WP reinforced PLA/PCL composite bioactive scaffolds are promising for load bearing bone defect repair.

Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy.

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

Bacterial diversity and biopotentials of Hamtah glacier cryoconites, Himalaya.

Cryoconite is a granular structure present on the glaciers and ice sheets found in polar regions including the Himalayas. It is composed of organic and inorganic matter which absorb solar radiations and reduce ice surface albedo, therefore impacting the melting and retreat of glaciers. Though climate warming has a serious impact on Himalayan glaciers, the biodiversity of sub-glacier ecosystems is poorly understood. Moreover, cryoconite holes are unique habitats for psychrophile biodiversity hotspots in the NW Himalayas, but unfortunately, studies on the microbial diversity of such habitats remain elusive. Therefore, the current study was designed to explore the bacterial diversity of the Hamtah Glacier Himalaya using both culturable and non-culturable approaches. The culturable bacterial count ranged from 2.0 × 103 to 8.8 × 105 colony-forming units (CFUs)/g at the different locations of the glacier. A total of 88 bacterial isolates were isolated using the culturable approach. Based on the 16S ribosomal RNA gene (16S rRNA), the identified species belong to seven genera, namely, Cryobacterium, Duganella, Janthinobacterium, Pseudomonas, Peribacillus, Psychrobacter, and Sphingomonas. In the non-culturable approach, high-throughput sequencing of 16S rRNA genes (using MiSeq) showed unique bacterial community profiles and represented 440 genera belonging to 20 phyla, namely, Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, Chloroflexi, Acidobacteria, Planctomycetes, Cyanobacteria, Verrucomicrobia, Spirochaetes, Elusimicrobia, Armatimonadetes, Gemmatimonadetes, Deinococcus-Thermus, Nitrospirae, Chlamydiae, Chlorobi, Deferribacteres, Fusobacteria, Lentisphaerae, and others. High relative abundances of Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were observed in the samples. Phototrophic (Cyanobacteria and Chloroflexi) and nitrifier (Nitrospirae) in bacterial populations indicated sustenance of the micro-ecosystem in the oligotrophic glacier environment. The isolates varied in their phenotypic characteristics, enzyme activities, and antibiotic sensitivity. Furthermore, the fatty acid profiles of bacterial isolates indicate the predominance of branched fatty acids. Iso-, anteiso-, unsaturated and saturated fatty acids together constituted a major proportion of the total fatty acid composition. High cold-adapted enzyme activities such as lipase and cellulase expressed by Cryobacterium arcticum (KY783365) and protease and cellulase activities by Pseudomonas sp. strains (KY783373, KY783377-79, KY783382) provide evidence of the possible applications of these organisms. Additionally, antibiotic tests indicated that most isolates were sensitive to antibiotics. In conclusion, the present study contributed for the first time to bacterial diversity and biopotentials of cryoconites of Hamtah Glacier, Himalayas. Furthermore, the cold-adapted enzymes and polyunsaturated fatty acids (PUFAs) may provide an opportunity for biotechnology in the Himalayas. Inductively coupled plasma mass spectrometry (ICPMS) analyses showed the presence of several elements in cryoconites, providing a clue for the accelerating melting and retreating of the Hamtah glacier.

Development of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality.

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82-0.84) and a balanced accuracy of 0.78 (95% CI 0.77-0.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40-0.74). Quantitative PCR validated LEF1-AS1's adaptability to be measured in hospital settings. Here, we demonstrate a promising predictive model for enhancing COVID-19 patient management.

Comparative Metabolomics and Network Pharmacology Analysis Reveal Shared Neuroprotective Mechanisms of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb.

Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., two nootropics, are recognized in Indian Ayurvedic texts. Studies have attempted to understand their action as memory enhancers and neuroprotectants, but many molecular aspects remain unknown. We propose that Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb. share common neuroprotective mechanisms. Mass spectrometry-based untargeted metabolomics and network pharmacology approach were used to identify potential protein targets for the metabolites from each extract. Phytochemical analyses and cell culture validation studies were also used to assess apoptosis and ROS activity using aqueous extracts prepared from both herbal powders. Further, docking studies were also performed using the LibDock protocol. Untargeted metabolomics and network pharmacology approach unveiled 2751 shared metabolites and 3439 and 2928 non-redundant metabolites from Bacopa monnieri and Centella asiatica extracts, respectively, suggesting a potential common neuroprotective mechanism among these extracts. Protein-target prediction highlighted 92.4% similarity among the proteins interacting with metabolites for these extracts. Among them, kinases mapped to MAPK, mTOR, and PI3K-AKT signaling pathways represented a predominant population. Our results highlight a significant similarity in the metabolome of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., and their potential protein targets may be attributed to their common neuroprotective functions.

Wild edible vegetables of ethnic communities of Mizoram (Northeast India): an ethnobotanical study in thrust of marketing potential.

BACKGROUND: Assessment of wild edible vegetables (WEVs) from the ethnobotanical approach is a significant key to understanding indigenous knowledge systems. The available literature has revealed a tremendous decline in knowledge of WEVs over the last few decades. The main purpose of this study was to document and analyse the traditional knowledge of WEVs among the two major ethnic groups of Mizoram regarding their use and the diversity associated with the importance of traditional medicines. Secondly, a market survey will be conducted to determine the status of available WEVs. METHODS: This study conducted an ethnobotanical survey among 72 informants through semi-structured interviews and questionnaires besides direct field observations. The documented data were quantitatively analysed using various ethnobotanical indices, including Informant's consensus factor (ICF), Fidelity level value (Fl), and Direct matrix ranking (DMR). A marketing survey was conducted in the Bara Bazar, Mizoram's most prominent local market. A total of 38 vendor informants were interviewed to observe and collect the price of commonly sold WEVs. RESULTS: A total of 70 WEVs, distributed in 58 genera under 36 families, were documented and identified. Of these, 33 WEVs were of medicinal importance. Leafy vegetables were documented as the most frequently consumed parts (55.71%). The majority (44.29%) of the plants documented were consumed in fried form. The highest level of agreement among informants for food used categories was observed for plants combined with dry fish (ICF = 1). The Informant's consensus factor (ICF) of disease categories ranges from 0.75 to 1, with the highest being reported for convulsion (ICF = 1), sleep inducer (ICF = 1), and antiseptic (ICF = 1). Picria fel-terrae was the most preferred plant for hypertension treatment (100% FL). Direct matrix ranking (DMR) indicated that Dysoxylum excelsum was highly utilized by the inhabitant for multipurpose species (DMR = 64). Jaccard similarity index (JI) between the two ethnic groups was revealed at 1.26. Forty-seven WEVs were found to be commercialized in the Bara Bazar market, Aizawl, with a price range from 0.1 to 2.4 USD. Ensete superbum was reported as near threatened per the IUCN Red List of Threatened Species. CONCLUSION: This work highlighted the importance and rich diversity of WEVs in Mizoram, which are presently used among different age groups for food and medicine. Informants have good knowledge of WEVs, which was shared to a great extent among the inhabitants; this legacy of traditional culture must be conserved. This study further suggests a priority setting for conserving multipurpose WEVs in human-inhabited sites, investigating the recorded species' nutritional properties and pharmacological activities.

Antimicrobial therapeutic protein extraction from fruit waste and recent trends in their utilization against infections.

Fruits are a very good source of various nutrients that can boost overall human health. In these days, the recovery of therapeutic compounds from different fruit wastes is trending in research, which might not only minimize the waste problem but also encounter a higher demand for various enzymes that could have antimicrobial properties against infectious diseases. The goal of this review is to focus on the recovery of therapeutic enzymes from fruit wastes and its present-day tendency for utilization. Here we discussed different parts of fruit waste, such as pulp, pomace, seed, kernel, peel, etc., that produce therapeutic enzymes like amylase, cellulose, lipase, laccase, pectinase, etc. These bioactive enzymes are present in different parts of fruit and could be used as therapeutics against various infectious diseases. This article provides a thorough knowledge compilation of therapeutic enzyme isolation from fruit waste on a single platform, distinctly informative, and significant review work on the topic that is envisioned to encourage further research ideas in these areas that are still under-explored. This paper explains the various aspects of enzyme isolation from fruit and vegetable waste and their biotherapeutic potential that could provide new insights into the development of biotherapeutics and attract the attention of researchers to enhance translational research magnitude further.

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

INTRODUCTION: Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. AIMS AND METHODS: We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. RESULTS: If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. CONCLUSIONS: Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. IMPLICATIONS: This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

Development of Simultaneous HPTLC Method and Validation for the Quality Assessment of Ayurvedic Formulation-Ayush Kvatha Churna by Using Marker Compound Rosmarinic Acid, Trans-Cinnamaldehyde and Piperine.

Ayurveda emphasizes the propagation of nature in maintaining health. In the present scenario, we have seen the faith of people in herbal drugs during the Covid 19 outbreak. The raises in the number of peoples have been using herbal drugs to boost immunity against infectious diseases shows the popularity of this ancient system of medicine. The standardization of Ayush Kvatha Churna (AKC), work set out to establish a straightforward, accurate and sensitive HPTLC method for the identification and quantification of marker compounds. The Rosmarinic acid, trans-Cinnamaldehyde and Piperine were used for the estimation of markers in Ayush Kvatha Churna by using HPTLC with a solvent system, consisting of Toluene: Ethyl acetate: Ethyl alcohol: Formic acid (5.6:2.4:2: 0.3 v/v/v/v). The Rf value 0.33 for Rosmarinic Acid, 0.69 for Piperine and 0.77 for trans-Cinnamaldehyde was observed and it is exactly complying with the corresponding bands in Ayush Kvatha Churna. The technique has been effectively verified and validated, enabling it to be used for the standardization or quantitative analysis of Rosmarinic acid, trans-Cinnamaldehyde and piperine in Ayush Kvatha Churna.

Microbiota-brain axis: Exploring the role of gut microbiota in psychiatric disorders - A comprehensive review.

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.

Optimizing methanol synthesis from CO2 using graphene-based heterogeneous photocatalyst under RSM and ANN-driven parametric optimization for achieving better suitability.

Assessment of the performance of linear and nonlinear regression-based methods for estimating in situ catalytic CO2 transformations employing TiO2/Cu coupled with hydrogen exfoliation graphene (HEG) has been investigated. The yield of methanol was thoroughly optimized and predicted using response surface methodology (RSM) and artificial neural network (ANN) model after rigorous experimentation and comparison. Amongst the different types of HEG loading from 10 to 40 wt%, the 30 wt% in the HEG-TiO2/Cu assisted photosynthetic catalyst was found to be successful in providing the highest conversion efficiency of methanol from CO2. The most influencing parameters, HEG dosing and inflow rate of CO2, were found to affect the conversion rate in the acidic reaction regime (at pH of 3). According to RSM and ANN, the optimum methanol yields were 36.3 mg g-1 of catalyst and 37.3 mg g-1 of catalyst, respectively. Through the comparison of performances using the least squared error analysis, the nonlinear regression-based ANN showed a better determination coefficient (overall R2 > 0.985) than the linear regression-based RSM model (overall R2 ∼ 0.97). Even though both models performed well, ANN, consisting of 9 neurons in the input and 1 hidden layer, could predict optimum results closer to RSM in terms of agreement with the experimental outcome.

Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.

Statistical estimation of noise induced hearing loss among the drivers in one of the most polluted cities of India.

In the present study, an attempt has been made to assess the impact of vehicular noise upon the 3-wheeler tempo drivers and to know whether there is any relationship between hearing loss and cumulative noise exposure. For this purpose, 3-wheeler tempo drivers (Exposed group) and non-commercial light motor vehicle car drivers (Unexposed group) were chosen as study subjects. Three traffic routes were selected to assess the noise level during waiting and running time in the exposed and unexposed groups. Among all three routes, the highest mean noise level (Leq) was observed on the Chowk to Dubagga route for waiting and en-route noise measurement. It was measured as 84.13 dB(A) and 86.36 dB(A) for waiting and en-route periods of 7.68 ± 3.46 and 31.05 ± 6.6 min, respectively. Cumulative noise exposure was found to be significantly different (p < 0.001) in all age groups of exposed and unexposed drivers. Audiometric tests have been performed over both exposed and unexposed groups. The regression analysis has been done keeping hearing loss among tempo drivers as the dependent variable and age (years) and Energy (Pa2 Hrs) as the independent variable using three different criteria of hearing loss definitions, i.e., World Health Organization, National Institute for Occupational Safety and Health (NIOSH), Occupational Safety and Health Administration criteria. Among these three criteria, the NIOSH criterion of hearing loss best explained the independent variables. It could explain the total variation in dependent variable by independent variable quite well, i.e., 68.1%. The finding showed a linear relationship between cumulative noise exposures (Pa2 Hrs) and the exposed group's hearing loss (dB), i.e., hearing loss increases with increasing noise dose. Based on the findings, two model equations were developed to identify the safe and unsafe noise levels with exposure time.

An overview of techniques for monitoring and compensating tool wear in micro-electrical discharge machining.

Micro-electrical discharge machining (µEDM) is severely affected by tool wear and its process variants, which can lead to compromised precision and dimensional disruptions in micro-part production. Several attempts have been made to address this problem by suggesting offline and online (real-time) tool wear compensation strategies. Research efforts in this area have intensified over the last 20 years. However, most methods proposed were applicable only for a few work-tool combinations and in limited input process parametric settings. Instead of tool wear compensation, several research articles have focused on strategies to reduce the negative impact of tool wear on the quality of fabricated parts. The present study systematically reviews various investigations conducted in this area and aims to add cutting-edge compensation for tool wear to future inquiries. The articles reviewed here are explored in detail. Critical findings/innovations are classified into four categories: tool wear in µEDM, tool wear compensation techniques, and offline and online compensation methods.

Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease.

The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the quality of health care, ischaemic heart disease remains the leading cause of death globally, owing to adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure. Therapeutic targets are urgently required for the protection and repair of the ischaemic heart. Moreover, personalized clinical biomarkers are necessary for clinical diagnosis, medical management and to inform the individual response to treatment. Non-coding RNAs (ncRNAs) deeply influence cardiovascular functions and contribute to communication between cells in the cardiac microenvironment and between the heart and other organs. As such, ncRNAs are candidates for translation into clinical practice. However, ncRNA biology has not yet been completely deciphered, given that classes and modes of action have emerged only in the past 5 years. In this Review, we discuss the latest discoveries from basic research on ncRNAs and highlight both the clinical value and the challenges underscoring the translation of these molecules as biomarkers and therapeutic regulators of the processes contributing to the initiation, progression and potentially the prevention or resolution of ischaemic heart disease and heart failure.

A Perspective on Various Facets of Nanoemulsions and its Commercial Utilities.

Nanotechnology is a captivating contemporary technology owing to its extensive range of potential applications. This study emphasizes nanomaterials, substances with a size <100 nm, offering better qualities than coarse particles. Nanoparticles have several advantages compared with conventional drug delivery methods, including enhanced bioavailability and a larger surface area because of their smaller particle size. These characteristics make the nanoparticles a viable clinical candidate. Controlled-release drug delivery systems and targeted drug delivery systems rely heavily on nanoparticles. Because traditional drug delivery methods fail to achieve targeted drug delivery, resulting in toxicity, low bioavailability, poor therapeutic outcomes, and so on, these drug nanoparticles excel in all these areas. Researchers are already interested in developing drug delivery systems such as niosomes, bilosomes, and dendrimers. Nanoemulsion is one of these technologies; nanoemulsions outperform traditional emulsions in terms of pharmacodynamics and pharmacokinetics. Nanoemulsion effectively surpasses the constraints of standard emulsions, primarily by offering enhanced bioavailability, reduced toxicity, improved absorption, and the potential to be used in targeted drug delivery or controlled-release drug delivery systems. This particular work explores several aspects of nanoemulsions, including their constituents, classification, techniques for preparation, criteria for assessment, commercial applications, and future prospects.

Unpacking Immune Modulation as a Site of Therapeutics Innovation for Nematode Parasite Wuchereria bancrofti: A Temporal Quantitative Phosphoproteomics Profiling of Macrophage Migration Inhibitory Factor 2.

Nematode infections are common in both humans and livestock, with major adverse planetary health and economic impacts. Wuchereria bancrofti is a parasitic nematode that causes lymphatic filariasis, a neglected tropical disease that can lead to severe disability and deformity worldwide. For the long-term survival of the bancroftian parasites in the host, a complex immune invasion strategy is involved through immunomodulation. Therefore, immunomodulation can serve as a site of research and innovation for molecular targets. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine crucial to the host antimicrobial alarm system and stress response. Interestingly, the nematode parasite W. bancrofti also produces two homologs of MIF (Wba-MIF1 and 2). Using a mass spectrometry-based phosphoproteomics approach, we report new findings on the immunomodulatory effect and signaling mechanism of Wba-MIF2 in macrophage cells. Accordingly, we observed 1201 phosphorylated sites on 467 proteins. Out of the 1201 phosphorylated sites, 1075, 117, and 9 were found on serine (S), threonine (T), and tyrosine (Y) residues, respectively. Our bioinformatics analysis led to identification of major pathways, including spliceosomes, T cell receptor signaling pathway, Th17 differentiation pathway, interleukin-17 signaling pathway, and insulin signaling pathway upon Wba-MIF2 treatment. Wba-MIF2 treatment also enriched CDK4, CDK1, and DNAPK kinases. The comparison of the signaling pathway of Wba-MIF2 with that of human-MIF suggests both share similar signaling pathways. These findings collectively offer new insights into the role and mechanism of Wba-MIF2 as an immunomodulator and inform future diagnostics and drug discovery research for W. bancrofti.