Primary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, remains an aggressively fatal infection with often ineffectual treatment avenues. This study reviews the antiamoebic efficacy of natural-derived compounds, including plant-based, marine-sourced, and nano-conjugated metabolites, bringing light to their potential as next-generation therapeutics. Notably, plant-derived kaempferol and diosgenin were found to induce programmed cell death (PCD) in N. fowleri via mitochondrial signalling and production of reactive oxidative species (ROS), without the added toxicity to normal human cell lines. Terpenes such as thymol and forskolin effectively targeted both trophozoites and cysts by disrupting intracellular signalling and cell membrane integrity. The ability to cross the blood-brain barrier (BBB) was exhibited by marine-derived oxasqualenoids and sesquiterpenes a key requirement for effective PAM therapy, with the added ability to induce apoptosis in trophozoites. These compounds interfere with critical pathogenic mechanisms, including phagocytosis, adhesion, and protease activity highlighting their potential for multi-targeted therapy. Compared to current PAM treatments, which are limited by toxicity and poor central nervous (CNS) penetration, these natural compounds offer a safer and potentially more effective alternative. Additionally, nanoconjugation significantly enhanced the compound bioavailability, brain-targeting, and retention, further amplifying their therapeutic potential. This comprehensive review aims to bring to the apogee, the scientific importance of these findings and lays the foundation for future drug development strategies that harness the structural diversity and mechanistic specificity of natural products for treating PAM.
Klebsiella pneumoniae is one of the most common opportunistic pathogens colonizing the preterm infant gut, and it is associated with neonatal infections. However, the use of antibiotics against infections can disrupt the gut microbiota and lead to emergence of antibiotic-resistant bacteria. Probiotics possess antimicrobial or antagonistic properties that play a key role in inhibiting pathogens. Probiotics (Bifidobacterium and Lactobacillus) could be a promising prophylactic or alternative therapy in aiding to curtail the spread of antibiotic-resistant bacteria in the gut and to overcome infection in preterm infants. This study aims to present findings on the antagonistic potential of probiotic strains against the isolated antibiotic-resistant Klebsiella pneumoniae from preterm infant stool samples. The antagonistic activity of these probiotic strains was assessed using cross-streak assay. Results demonstrated that Bifidobacterium longum subsp. infantis JCM 1222T, and Lactiplantibacillus plantarum JCM11125 exhibited remarkable antagonistic effects on Klebsiella pneumoniae isolated from preterm infant stools, while the antagonistic activity exhibited by Bifidobacterium bifidum JCM 1255T was weaker. Overall, our findings showed that selected probiotic strains could be a promising adjunct or preventive strategy for the management of Klebsiella pneumoniae infections in preterm infants, especially in settings where antibiotic resistance is prevalent. Nonetheless, future in vivo studies and clinical trials are essential to validate these findings, as well as to determine the optimal combinations, dosages, and safety profiles for their clinical applicability for neonatal use.
Streptomyces species are among the most prolific natural sources of antibiotics and other bioactive secondary metabolites, supporting major therapeutic advances, including streptomycin and ivermectin. In addition to their ecological role as saprophytic decomposers, they remain central to modern medicine and agriculture, with nearly two-thirds of clinically used antibiotics originating directly or indirectly from this genus. Recent progress in genome sequencing, CRISPR-Cas9 editing, and synthetic biology has expanded our ability to modify Streptomyces genomes, activate silent biosynthetic gene clusters, remove competing pathways, and increase metabolite output. Yet, industrial use of these bacteria continues to be difficult due to their complex multicellular life cycle and pronounced phenotypic heterogeneity. Even genetically identical cells display differences in germination, growth, and metabolic activity, leading to inconsistent fermentation performance and variable yields. More recent studies have shown that this heterogeneity is not simply a technical barrier but a beneficial ecological strategy that improves survival in changing environments. These findings underscore the need to understand the spatial and temporal diversity that shapes Streptomyces biology. New single-cell technologies, including microfluidics and Raman spectroscopy, now allow direct observation of developmental processes, spatial mapping of metabolite production, and high-resolution screening of superior producer strains. This review summarises current advances in engineering Streptomyces and examines how single-cell approaches are transforming our understanding of their variability. By combining genetic tools with precise phenotypic analysis, researchers are moving toward more consistent and scalable production systems for valuable natural products.
Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world. Despite extensive research, its aetiology and pathogenesis remain poorly understood, often leading to delayed or missed diagnoses, especially in early-onset cases. One of the important hallmarks of PD is the progressive loss of dopaminergic neurons in the substantia nigra, which underlies the manifestation of motor symptoms. Current therapeutic interventions, which primarily offer symptomatic relief, do not alter the deteriorating course of the disease. These limitations have led to a greater emphasis on regenerating dopaminergic neurons as a potential approach for PD management. Mammals, however, exhibit limited reparative capacity in renewing cellular components of the central nervous system (CNS), making mammalian-based models unsuited for the understanding of neuroregeneration. As such, the zebrafish (Danio rerio) has emerged as a powerful model for neuroregeneration studies given its robust neurogenic potential, high proliferative capacity, and significant genetic and structural homology to the human brain. This review aimed at highlighting current findings on zebrafish neuroregeneration, with particular emphasis on 1) cellular responses and neuroinflammation following the loss of neurons and 2) brain repair through the regeneration of new neurons through sequential stages of progenitor cell proliferation, migration, and differentiation at the injured brain regions. The latest findings on the conserved neuroregenerative mechanisms in zebrafish further imply translational potential into novel therapeutic strategies against PD, such as drug discovery and activation of endogenous repair pathways. By contrasting the mammalian limitations, this review underscores advances in zebrafish neuroregeneration which could provide new therapeutic avenues for PD.
Polycystic ovary syndrome (PCOS) is a multifactorial endocrine metabolic disorder affecting up to one in ten women of reproductive age, with implications on fertility, metabolic health, and quality of life. Recent evidence has shown that gut microbiota dysbiosis plays a role in the PCOS pathophysiology. Based on the 25 articles extracted from PubMed, Ovid Medline, and Scopus (2020–2025), this review reveals that PCOS is consistently associated with reduced gut microbial α-diversity, distinct β-diversity clustering, and compositional shifts marked by depletion of beneficial taxa. These dysbiosis correlate with PCOS phenotypes such as insulin resistance, hyperandrogenism, dyslipidemia, and chronic inflammation via mechanisms involving impaired short-chain fatty acid production, disrupted bile acid metabolism, increased intestinal permeability, and immune-mediated dysregulation of the hypothalamic–pituitary–ovarian axis. Recognising the increasing role of the gut microbiome in PCOS highlights its systemic pathology and points towards the opportunities for microbiota-targeted therapies that address underlying pathophysiological mechanisms rather than symptomatic care alone.
