Search Results (289)

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Circular RNAs (circRNAs) are covalently closed RNA molecules generated through a non-canonical splicing event known as back-splicing. This particular class of non-coding RNAs has attracted growing interest due to its evolutionary conservation across eukaryotes, high expression in the central nervous system, and frequent dysregulation in various pathological conditions, including cancer. Traditionally, circRNAs have been characterised by their ability to function as microRNA (miRNA) and protein sponges. However, recent discoveries from multiple research groups have uncovered a novel and potentially transformative mechanism of action: the direct interaction of circRNAs with messenger RNAs (mRNAs) to regulate their fate. These interactions can influence mRNA stability and translation, revealing a new layer of post-transcriptional gene regulation. In this review, we present and analyse the latest evidence supporting the emerging role of circRNAs in diverse biological contexts. We highlight the growing body of research demonstrating circRNA-mRNA interactions as a functional regulatory mechanism and explore their involvement in key physiological and pathophysiological processes. Understanding this novel mechanism expands our knowledge of RNA-based regulation and opens new opportunities for therapeutic strategies targeting circRNA-mRNA networks in human disease. Full article

Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as critical modulators of this pathway. Accumulating evidence indicates that specific circRNAs regulate Wnt/β-catenin signaling by sponging microRNAs, interacting with RNA-binding proteins, modulating protein function, and altering the expression of pathway components. Some circRNAs are also subject to feedback regulation by Wnt signaling itself. Clinically, tumor-associated circRNAs are present in body fluids and correlate with disease stage, metastatic burden, and patient survival, underscoring their potential as early and minimally invasive biomarkers. Moreover, targeting oncogenic circRNAs has shown promise in preclinical models of Wnt-driven gastrointestinal malignancies. In this review, we summarize the current understanding of the interplay between circRNAs and Wnt/β-catenin signaling in gastric and esophageal cancers. We discuss the translational challenges and emerging opportunities for biomarker development and targeted therapy. Full article

T-cadherin (CDH13) is an atypical, glycosyl-phosphatidylinositol-anchored cadherin with functions ranging from axon guidance and vascular patterning to adipokine signaling and cell-fate specification. Originally identified as a homophilic cue for migrating neural crest cells, projecting axons, and growing blood vessels, it later emerged as a dual metabolic receptor for cardioprotective high-molecular-weight adiponectin and atherogenic low-density lipoproteins. We recently showed that mesenchymal stem/stromal cells lacking T-cadherin are predisposed to adipogenesis, underscoring its role in lineage choice. Emerging evidence indicates that CDH13 expression and function are fine-tuned by non-coding RNAs (ncRNAs). MiR-199b-5p, miR-377-3p, miR-23a/27a/24-2, and the miR-142 family directly bind CDH13 3′-UTR or its epigenetic regulators, affecting transcription or accelerating decay. Long non-coding RNAs (lncRNAs), including antisense transcripts CDH13-AS1/AS2, brain-restricted FEDORA, and context-dependent LINC00707 and UPAT, either sponge these miRNAs or recruit DNMT/TET enzymes to the CDH13 promoter. Circular RNAs (circRNAs), i.e.circCDH13 and circ_0000119, can add a third level of complexity by sequestering miRNA repressors or boosting DNMT1. Collectively, this ncRNA circuitry regulates T-cadherin across cardiovascular, metabolic, oncogenic, and neurodegenerative conditions. This review integrates both experimentally validated data and in silico predictions to map the ncRNA-CDH13 crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics. Full article

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play crucial roles in regulating gene expression, and their dysregulation is implicated in various human diseases. Over the years, several research groups have identified miRNAs as promising therapeutic targets for intervention. Therapeutic strategies involve either overexpression or knockdown of specific miRNAs. This review aims to provide a comprehensive overview of synthetic poly-miRNAs and miRNA sponges, highlighting their therapeutic applications. It begins with an introduction to miRNAs and their role in human diseases, followed by a detailed discussion on synthetic poly-miRNAs and miRNA sponges by exploring their application in cardiovascular, inflammatory, autoimmune, and metabolic disorders, as well as in cancer therapy. Additionally, strategies for targeted delivery, challenges, and limitations of these therapies are addressed. Full article

There is a growing need for eco-friendly methods to control disease-carrying insects. The present study aimed to investigate the larvicidal activity of methanolic extracts and their various fractions from a plant, Artemisia arborescens L., and a marine sponge, Hyrtios erectus, against the mosquito, Culex pipiens L. Crude methanolic extracts of A. arborescens and H. erectus were prepared by maceration and successive fractionation were obtained using the liquid–liquid partition of crude extracts. The larvicidal activity of the extracts and their fractions was determined according to the WHO standard method. The results revealed that the n-hexane fraction of A. arborescens exhibited the highest larvicidal activity (LC₅₀ 346.74 μg/mL), exceeding the efficacy of the crude extract and other fractions. Furthermore, the sponge’s n-hexane (LC₅₀ 68.39 μg/mL), chloroform (LC₅₀ 63.03 μg/mL), and n-butanol (LC₅₀ 71.23 μg/mL) fractions showed a significant 3.9 to 4.5 times increase in the larvicidal potency compared to its crude extract (LC₅₀ = 280.74 μg/mL). The safety of the sponge extracts was tested in the embryos of zebrafish as a non-target organism. In this regard, the crude methanolic extract and n-butanol fraction exhibited weak toxicity and chloroform fraction showed no detectable toxicity. This study suggests the H. erectus sponge as a source for developing safe natural substitutes for use in the battle against Cx. pipiens mosquito, which may help in reducing the spread of mosquito vectors and mosquito-borne diseases. Full article

MicroRNAs (miRNAs) are small RNA molecules that do not have coding functions but play essential roles in various biological processes. In lung cancer, miRNAs affect the processes of tumor initiation, progression, metastasis, and resistance to treatment by regulating gene expression. Tumor-suppressive miRNAs inhibit oncogenic pathways, while oncogenic miRNAs, known as oncomiRs, promote malignant transformation and tumor growth. These dual roles position miRNAs as critical players in lung cancer biology. Studies in recent years have shown the significant potential of miRNAs as both prognostic and diagnostic biomarkers. Circulating miRNAs in plasma or sputum demonstrate specificity and sensitivity in detecting early-stage lung cancer. Liquid biopsy-based miRNA panels distinguish malignant from benign lesions, and specific miRNA expression patterns correlate with disease progression, response to treatment, and overall survival. Therapeutically, miRNAs hold promise for targeted interventions. Strategies such as miRNA replacement therapy using mimics for tumor-suppressive miRNAs and inhibition of oncomiRs with antagomiRs or miRNA sponges have shown preclinical success. Key miRNAs, including the let-7 family, miR-34a, and miR-21, are under investigation for their therapeutic potential. It should be emphasized that delivery difficulties, side effects, and limited stability of therapeutic miRNA molecules remain obstacles to their clinical use. This article examines the roles of miRNAs in lung cancer by indicating their mechanisms of action, diagnostic significance, and therapeutic potential. By addressing current limitations, miRNA-based approaches could revolutionize lung cancer management, offering precise, personalized, and minimally invasive solutions for diagnosis and treatment. Full article

Nanotheranostics—where nanoscale materials serve both diagnostic and therapeutic functions—are rapidly transforming gene therapy by tackling critical delivery challenges. This review explores the design and engineering of various nanoparticle systems (lipid-based, polymeric, inorganic, and hybrid) to enhance stability, targeting, and endosomal escape of genetic payloads. We discuss how real-time imaging capabilities integrated into these platforms enable precise localization and controlled release of genes, improving treatment efficacy while reducing off-target effects. Key strategies to overcome delivery barriers (such as proton sponge effect and photothermal disruption) and to achieve nuclear localization are highlighted, along with recent advances in stimuli-responsive systems that facilitate spatiotemporal control of gene expression. Clinical trials and preclinical studies demonstrate the expanding role of nanotheranostics in managing cancer, inherited disorders, and cardiovascular and neurological diseases. We further address regulatory and manufacturing hurdles that must be overcome for the widespread clinical adoption of nanoparticle-based gene therapies. By synthesizing recent progress and ongoing challenges, this review underscores the transformative potential of nanotheranostics for effective, targeted, and image-guided gene delivery. Full article

In 2022, an outbreak of fungal rot disease affected luffa crops in Shanghai and Zhejiang Province. Infected plants exhibited symptoms including yellowing, chlorosis, wilting, and water-soaked occurred on leaves and fruits. Dark brown, concave lesions developed, often accompanied by white or pale pink mold under moist conditions. Fourteen pathogen strains, morphologically resembling Fusarium species, were isolated. Molecular analysis confirmed Fusarium incarnatum as the causative agent. Pathogenicity tests on luffa plants fulfilled Koch’s postulates, with inoculated plants displaying the same symptoms. Re-isolation of the fungus from the inoculated plants confirmed its role in the disease. To our knowledge, this is the first report of F. incarnatum causing leaf spot and fruit rot on luffa in China. Moreover, the soil bacterial strain Bacillus velezensis BV171 displayed strong inhibition of F. incarnatum mycelia growth and promoted the growth of sponge gourd plants. These findings lay the foundation for the development of diagnostic tools, disease management strategies, and the breeding of resistant luffa varieties. Full article

Circular RNAs (circRNAs) make up approximately 10% of the human transcriptome. CircRNAs belong to the broad group of non-coding RNAs and characteristically are formed by backsplicing into a stable circular loop. Their main role is to regulate transcription through the inhibition of miRNAs’ expression, termed miRNA sponging. CircRNAs promote tumorigenesis/lymphomagenesis by competitively binding to miRNAs at miRNA binding sites. In diffuse large B-cell lymphoma (DLBCL), several circRNAs have been identified and their expression is related to both progression and response to therapy. DLBCL is the most prevalent and aggressive subtype of B-cell lymphomas and accounts for about 25% to 30% of all non-Hodgkin lymphomas. DLBCL displays great heterogeneity concerning histopathology, biology, and genetics. Patients who have relapsed or have refractory disease after first-line therapy have a very poor prognosis, demonstrating an important unmet need for new treatment options. As more circRNAs are identified in the future, we will better understand their biological roles and potential use in treating cancer, including DLBCL. For example, circAmotl1 promotes nuclear translocation of MYC and upregulation of translational targets of MYC, thus enhancing lymphomagenesis. Another example is circAPC, which is significantly downregulated in DLBCL and correlates with disease aggressiveness and poor prognosis. CircAPC increases expression of the host gene adenomatous polyposis coli (APC), and in doing so inactivates the canonical Wnt/β-catenin signaling and restrains DLBCL growth. MiRNAs belong to the non-coding regulatory molecules that significantly contribute to lymphomagenesis through their target mRNAs. In DLBCL, among the highly expressed miRNAs, are miR-155-5p and miR-21-5p, which regulate NF-ĸB and PI3K/AKT signaling pathways. The aim of this review is to describe the function and mechanism of regulation of circRNAs on miRNAs’ expression in DLBCL. This will help us to better understand the regulatory network of circRNA/miRNA/mRNA, and to propose novel therapeutic targets to treat DLBCL. Full article

The frequent occurrence of disasters has brought significant challenges to increasingly complex urban systems. Resilient city planning and construction has emerged as a new paradigm for dealing with the growing risks. Infrastructure systems like transportation, lifelines, flood control, and drainage are essential to the operation of a city during disasters. It is necessary to measure how risks affect these systems’ resilience at different spatial scales. This paper develops an infrastructure risk and resilience evaluation index system in city and urban areas based on resilience characteristics. Then, a comprehensive infrastructure resilience evaluation is established based on the risk–resilience coupling mechanism. The overall characteristics of comprehensive infrastructure resilience are then identified. The resilience transmission level and the causes of resilience effects are analyzed based on the principle of resilience scale. Additionally, infrastructure resilience enhancement strategies under different risk scenarios are proposed. In the empirical study of Zhengzhou City, comprehensive infrastructure resilience shows significant clustering in the city area. It is high in the central city and low in the periphery. Specifically, it is relatively high in the southern and northwestern parts of the airport economy zone (AEZ) and low in the center. The leading driving factors in urban areas are risk factors like flood and drought, hazardous materials, infectious diseases, and epidemics, while resilience factors include transportation networks, sponge city construction, municipal pipe networks, and fire protection. This study proposes a “risk-resilience” coupling framework to evaluate and analyze multi-hazard risks and the multi-system resilience of urban infrastructure across multi-level spatial scales. It provides an empirical resilience evaluation framework and enhancement strategies, complementing existing individual dimensional risk or resilience studies. The findings could offer visualized spatial results to support the decision-making in Zhengzhou’s resilient city planning outline and infrastructure special planning and provide references for resilience assessment and planning in similar cities. Full article

Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation. Full article

Galectins are widely distributed throughout the animal kingdom, from marine sponges to mammals. Galectins are a family of soluble lectins that specifically recognize β-galactoside-containing glycans and are categorized into three subgroups based on the number and function of their carbohydrate recognition domains (CRDs). The interaction of galectins with specific ligands mediates a wide range of biological activities, depending on the cell type, tissue context, expression levels of individual galectin, and receptor involvement. Galectins affect various immune cell processes through both intracellular and extracellular mechanisms and play roles in processes, such as apoptosis, angiogenesis, and fibrosis. Their importance has increased in recent years because they are recognized as biomarkers, therapeutic agents, and drug targets, with many other applications in conditions such as cardiovascular diseases and cancer. However, little is known about the involvement of galectins in liver diseases. Here, we review the functions of various galectins and evaluate their roles in liver diseases. Full article

As global demand for sheep products increases, improving reproductive efficiency and lamb growth performance has become a priority for sheep farmers. Artificial insemination (AI) offers several advantages over natural mating, including improved genetic selection and disease control. This study contributes to understanding the impact of different mating methods and semen preservation techniques on reproductive performance and growth traits in Palestinian Assaf sheep under local breeding conditions. The research included 123 adult Assaf ewes from two farms, which were hormonally synchronized and divided into three groups for different reproductive biotechnologies. Group 1 (G1) comprised 50 ewes inseminated with frozen semen straws, while Group 2 (G2) had 37 ewes inseminated with fresh semen from genetically superior rams. Both G1 and G2 used 0.5 mL straws containing 250 million sperm, with insemination occurring 48 h post sponge removal and eCG hormone injection. Group 3 (G3) consisted of 36 ewes that underwent natural mating at a ratio of 1 ram to 6 ewes. The study revealed that insemination methods significantly affected fertility rates (45.4, 61.1, and 71.9% for G1, G2, and G3, respectively; p < 0.05). Artificial insemination notably enhanced lamb performance indicators (p < 0.05), although it did not significantly influence prolific lambing (p > 0.05). Prolific lambing significantly impacted birth weight, weaning weight, and average daily gain at 60 days across all groups (p < 0.05), but not the average daily gain or final weight at 180 days (p > 0.05). The management system significantly affected birth and weaning weights at 60 days (p < 0.05), but not the final weight at 180 days or prolific lambing (p > 0.05). Lamb sex significantly influenced average daily gains at 60 and 180 days, as well as final weight at 180 days (p < 0.05). The findings suggest that, while artificial insemination with semen from elite rams may reduce fertility rates, it significantly improves lamb performance rates. In conclusion, our study demonstrates that, while natural mating offers higher fertility rates, AI with fresh semen can be a valuable tool for improving lamb growth performance in Palestinian Assaf sheep. These findings provide valuable insights for sheep farmers in the region to optimize reproductive strategies and enhance lamb production Full article

Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against Leishmania major promastigotes, with IC₅₀ values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL. Full article