Hyaluronic acid: comprehensive review of a multifunctional biopolymer

Abstract Background Hyaluronic acid (HA) has a broad range of cosmetic and therapeutic applications due to its unique physicochemical properties and involvement in various essential biological processes, including cell signaling, wound reparation, and tissue regeneration. Main body In this review, we provide a comprehensive overview of HA, including its history, physicochemical properties, roles, molecular biology, and biochemistry (including occurrence, biosynthesis, and degradation), as well as its chemical modifications and conventional and emerging production methods. We also examine HA's medical, pharmaceutical, and cosmetic applications and its derivatives in arthrology, ophthalmology, wound healing, odontology, oncology, drug delivery, 3D bioprinting, and cosmetology. Finally, we discuss the potential role of HA in preventing Covid-19. Conclusion Hyaluronic acid, a naturally found substance, has shown immense potential in the clinic. Thus, it is imperative to highlight its applications in the diverse fields impacting the lives of patients and healthy individuals

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Background: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. Aim: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. Methodology: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. Results: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. Conclusion: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models

A comprehensive review of key factors affecting the efficacy of antibody drug conjugate

Antibody Drug Conjugate (ADC) is an emerging technology to overcome the limitations of chemotherapy by selectively targeting the cancer cells. ADC binds with an antigen, specifically over expressed on the surface of cancer cells, results decrease in bystander effect and increase in therapeutic index. The potency of an ideal ADC is entirely depending on several physicochemical factors such as site of conjugation, molecular weight, linker length, Steric hinderance, half-life, conjugation method, binding energy and so on. Inspite of the fact that there is more than 100 of ADCs are in clinical trial only 14 ADCs are approved by FDA for clinical use. However, to design an ideal ADC is still challenging and there is much more to be done. Here in this review, we have discussed the key components along with their significant role or contribution towards the efficacy of an ADC. Moreover, we also explained about the recent advancement in the conjugation method. Additionally, we spotlit the mode of action of an ADC, recent challenges, and future perspective regarding ADC. The profound knowledge regarding key components and their properties will help in the synthesis or production of different engineered ADCs. Therefore, contributes to develop an ADC with low safety concern and high therapeutic index. We hope this review will improve the understanding and encourage the practicing of research in anticancer ADCs development

Phytochemical Investigation, Antimicrobial, Antioxidant and Anticancer Activities of Acer cappadocicum Gled

The appearance of novel microbial resistance, diverse cancer ailment and several other morbidities such as appetite loss, hair loss, anemia, cell damage, etc., are among most critical situation that keeps the phytochemical quest on. Thus, this study characterized the antimicrobial, antioxidant, and anticancer potentials of a rarely accessed Acer cappadocicum gled (AC) population thriving in a remote Palas Valley in northern Pakistan. Leaf extracts of the plant were prepared in organic solvents with different polarities through maceration. Extracts were subjected to antimicrobial, antioxidant, and anticancer activities using agar well, DPPH and cell viability assays. A. cappadocicum methanolic extract (ACM) significantly inhibited bacterial growth, followed by n-butanolic extract (ACB) with the second-highest bacterial inhibition. Similar activity was observed against mycelial growth inhibition in plant-fungal pathogen by ACM and ACB. However, human pathogenic fungi did not affect much by extracts. In antioxidant assessment, the chloroform extract (ACC) showed strong scavenging activity and in cytotoxic evaluation, extracts restricted growth proliferation in cancer cells. The inhibitory evidence of extracts, potent scavenging ability, and low cell viability of human-derived cell lines supports the antimicrobial, antioxidant and anticancerous potential of A. cappadocicum. It advances our quest for natural product research

Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips

The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS

Evaluation of Antimicrobial and Anticancer Activities of Selected Medicinal Plants of Himalayas, Pakistan

Medicinal plants are known for their diverse use in the traditional medicine of the Himalayan region of Pakistan. The present study is designed to investigate the anticancer and antimicrobial activities of Prunus cornuta and Quercus semicarpifolia. The anticancer activity was performed using cancerous human cell lines (HepG2, Caco-2, A549, MDA-MB-231, and NCI-H1437 carcinoma cells), while the antimicrobial activity was conducted with the agar-well diffusion method. Furthermore, toxicity studies were performed on alveolar and renal primary epithelial cells. Initially, different extracts were prepared by maceration techniques using n-hexane, chloroform, ethyl acetate, butanol, and methanol. The preliminary phytochemical screening showed the presence of secondary metabolites such as alkaloids, tannins, saponins, flavonoids, glycosides, and quinones. The chloroform extract of P. cornuta (PCC) exhibited significant inhibitory activity against Acinetobacter baumannii (16 mm) and Salmonella enterica (14.5 mm). The A. baumannii and S. enterica strains appeared highly susceptible to n-hexane extract of P. cornuta (PCN) with an antibacterial effect of 15 mm and 15.5 mm, respectively. The results also showed that the methanolic extracts of Quercus semecarpifolia (QSM) exhibited considerable antibacterial inhibitory activity in A. baumannii (18 mm), Escherichia coli (15 mm). The QSN and QSE extracts also showed good inhibition in A. baumannii with a 16 mm zone of inhibition. The Rhizopus oryzae strain has shown remarkable mycelial inhibition by PCM and QSN with 16 mm and 21 mm inhibition, respectively. Furthermore, the extracts of P. cornuta and Q. semicarpifolia exhibited prominent growth inhibition of breast (MDA-MB-231) and lung (A549) carcinoma cells with 19–30% and 22–39% cell viabilities, respectively. The gut cell line survival was also significantly inhibited by Q. semicarpifolia (24–34%). The findings of this study provide valuable information for the future development of new antibacterial and anticancer medicinal agents from P. cornuta and Q. semicarpifolia extracts