Shivaswamy Umamaheshwari

Background: Candida species are among the most important opportunistic fungal pathogens responsible for superficial mucosal infections and life-threatening invasive candidiasis, particularly in immunocompromised individuals. The increasing prevalence of antifungal resistance, biofilm-associated tolerance, and the emergence of multidrug-resistant species such as Candida auris have highlighted the need for alternative or adjunctive therapeutic strategies. Probiotics have emerged as promising microbiome-based interventions owing to their ability to inhibit Candida growth, suppress virulence traits, restore microbial homeostasis, and modulate host immune responses. Methods: This systematic review comprehensively evaluated the experimental and mechanistic evidence regarding the anti- Candida activity of probiotics and probiotic-derived products. A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 1 January 2015 and 5 January 2026 in accordance with PRISMA 2020 guidelines. Studies meeting the predefined eligibility criteria were included in the qualitative synthesis. Results: Eighteen studies met the predefined eligibility criteria. Most studies investigated Lactobacillus species, followed by Bifidobacterium , Saccharomyces , and probiotic-derived metabolites or postbiotics, using predominantly in vitro models with limited in vivo evidence. Across studies, probiotics consistently demonstrated anti- Candida activity through inhibition of fungal growth, adhesion, yeast-to-hyphal transition, biofilm formation, and virulence-associated gene expression. Additional mechanisms included the production of antimicrobial metabolites, competitive exclusion, immune modulation, enhancement of epithelial barrier function, and restoration of microbial homeostasis. Emerging evidence also supports the antifungal potential of postbiotics and activity against non-albicans Candida species and Candida auris , although available evidence remains limited. Considerable heterogeneity in probiotic strains, experimental models, methodologies, and outcome measures precluded quantitative meta-analysis. Conclusions: Current evidence supports probiotics and postbiotics as promising microbiome-based strategies for reducing Candida pathogenicity; however, the available evidence remains predominantly preclinical. Well-designed clinical studies are required to establish strain-specific efficacy, optimal formulations, dosing strategies, safety, and therapeutic applicability before routine clinical implementation. Systematic review registration: https://www.crd.york.ac.uk/prospero/view/CRD420261278363 , identifier CRD420261278363.

Background: Invasive and mucosal infections caused by Candida species continue to pose a significant global health burden, particularly due to the species’ increasing resistance to conventional antifungal agents. This systematic review evaluates the antifungal potential of pyrrolidine-based derivatives, focusing on structure–activity relationships, mechanisms of action, and activity against Candida species. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2015 and January 2026, following PRISMA guidelines and registered in PROSPERO (CRD420261279035). Studies reporting in vitro, in vivo, or in silico evaluation of pyrrolidine derivatives against Candida species were included. Data extraction and risk-of-bias assessment were performed using predefined criteria. Results: Twelve studies met the inclusion criteria, describing diverse pyrrolidine-based scaffolds, including spirooxindole, dispiro, triazole-linked, tetrazole, and quinoline-fused derivatives. The compounds demonstrated antifungal activity against multiple Candida species, including resistant isolates with minimum inhibitory concentrations ranging from approximately 0.5 to 16 µg/mL. Several derivatives showed comparable activity to standard antifungal agents under the reported experimental conditions. Mechanistic investigations indicated inhibition of biofilm formation, disruption of fungal cell wall and membrane integrity, suppression of hyphal transition, and modulation of virulence-associated pathways. Multi-mechanism antifungal effects were reported across different structural classes. Conclusions: Pyrrolidine-based derivatives represent promising antifungal scaffolds with potent activity against Candida species and associated virulence factors. However, limited in vivo validation and insufficient pharmacokinetic and toxicity data remain major barriers to clinical translation. Further optimization of structure–activity relationships and comprehensive preclinical evaluation are required to advance these scaffolds toward therapeutic development.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood–brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

Aim: Effective toothbrushing is the most simple way to maintain a child’s oral hygiene for a cavity-free mouth. Yet, most children find it an uninteresting task and they fail to understand its scientific basis. Augmented reality (A-R)-assisted toothbrushes for pediatric population are commercially available to make toothbrushing interactive, interesting, and educative for the child, aided by gamification providing an interactive videogame platform between the real and the virtual world. The aim of the study was to evaluate the efficacy of A-R-assisted brushing experience of children with respect to fluorescence imaging data and plaque Streptococcus mutans count at clinical and microbiological levels, respectively. Materials and Methods: A total of 32 children in the age group of 6-8 years were included and allocated in two study groups (A-R-assisted toothbrushing and manual toothbrushing). Fluorescence-based lesion area scoring was done using FC, Duerr Dental, Vistaproof, Germany. Microbiological analysis of plaque Streptococcus mutans was done to evaluate change in bacterial count. The parameters were recorded again after two weeks. Pre- and post-intervention scores were subjected to statistical analysis. Results: Significantly higher reduction of fluorescent scores and mean bacterial count were found in A-R-assisted tooth-brushing group when compared to that of manual toothbrushing. Conclusion: Based on the findings of the study, A-R-assisted toothbrushing proves to be an effective tool for motivating and maintaining oral hygiene among children and efforts should be made in incorporating this practice in daily domestic healthcare.