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This study aims to biosynthesize zinc oxide nanoparticles using aqueous leaf extracts of Cnidoscolus aconitifolius and investigate their biological activities. UV-Vis Spectroscopy, FT-IR, SEM and TEM were used for characterization. The antioxidant properties were determined using H 2 O 2 , NO, ABTS, FRAP and DPPH scavenging assays. For anti-inflammatory activities, membrane stabilization, albumin denaturation and proteinase inhibitory activity were assayed. The antibacterial effect was tested using well diffusion method. Statistical analyses were done using ANOVA. Synthesized nanoparticles showed an intensity peak at 378 nm in UV-Vis Spectroscopy. FT-IR shows the presence of O-H stretching, C = C bending, O-H bending and C-N stretching functional groups of the stabilizing action of the plant extract on the surface of the nanoparticles. NPs were shown to be spherical by SEM analysis, and the sizes were 100 nm by TEM analysis. The antioxidant properties of ZnO NPs compared to ascorbic acid standard showed significant antioxidant potential in H 2 O 2 , NO, ABTS, FRAP and DPPH scavenging assays. ZnO NPs showed excellent anti-inflammatory activity with the synthesized ZnO NPs performing better in membrane stabilization. Clinical pathogens were inhibited by ZnO NPs when compared with Cefuroxime, a standard drug. These efficient biological activities could be utilized in several biological applications.

Malaria, caused by Plasmodium parasites, remains a global health burden, with drug resistance threatening control efforts. CRISPR-Cas technologies, particularly CRISPR-Cas9, have transformed malaria research by enabling precise genetic manipulations to study antimalarial resistance mechanisms, develop novel therapeutics and enhance diagnostics. A systematic literature search (2015-2025) across Web of Science, Scopus and PubMed identified 39 peer-reviewed studies utilising CRISPR-Cas to investigate antimalarial drug resistance in Plasmodium species. Data were extracted on study design, genetic manipulations, target genes, resistance mechanisms and outcomes. CRISPR-Cas9 was the dominant tool (84.6%), primarily used for point mutations (PfK13C580Y, PfCRT K76T), gene knockouts and integrations in P. falciparum (87.2%) and P. berghei (12.8%). Key resistance mechanisms included drug efflux (PfCRT, PfMDR1), reduced binding affinity (PfDHODH, DHFR), metabolic compensation (PfDHODH CNV) and impaired haemoglobin trafficking (PfK13, UBP-1). Novel mediators like PfCARL and PfExo were identified, alongside compensatory mutations mitigating fitness costs. High-throughput screening (BarSeq) and diagnostics (SHERLOCK, CRISPR-Cas 12a) enhanced resistance surveillance. Challenges included low editing efficiency in nonasexual stages, limited P. vivax tools, off-target risks and scalability constraints. CRISPR-Cas technologies have elucidated critical resistance pathways and supported innovative diagnostics, but challenges persist. Future advancements in base editing, omics integration and in vivo models will expand CRISPR's utility in nonfalciparum species and field isolates, informing novel antimalarials and surveillance strategies to combat drug-resistant malaria.

Background Human papillomavirus (HPV) and human immunodeficiency virus (HIV) co-infection present a significant impact on women's health globally, especially in immunocompromised individuals. HIV-induced immunosuppression promotes the persistence of high-risk HPV infection and increased the progression to cervical cancer. The aim of this systematic review was to assessed the impact of HPV/HIV co-infection on the prevalence and distribution of HR-HPV genotypes, the level of immunosuppression and expression of cervical cancer biomarkers. Method The article selection method for this review was based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The total of eighty-four (84) articles from standard electronic databases mainly Web of Science, PubMed, and Scopus were extracted and reviewed. The articles were published in English between 2008 and 2024 and comprised a total of 80023 participants. Results The HR-HPV genotypes reported across various studies include HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 70, 73, and 82. Among HIV positive individuals, the most common circulating HR-HPV genotypes were HPV16, 18, 45, 35, and 58, accounted for 11%, 10%, 9%, 8%, and 8% of cases, respectively. Approximately 29.1% and 30.0% of patients had CD4 counts of 200–400 cells/L and 300–400 cells/L, respectively. The most commonly reported cervical cancer biomarkers were p16INK4a and Ki-67, according to the analysis. Conclusion The findings indicate high prevalence of multiple HR-HPV genotypes among HIV positive individuals, indicating the impact of HPV/HIV co-infection on immunosuppression and persistence of HPV infection. The expression of cervical cancer biomarker such as p16INK4a and Ki-67 emphasized target screening and early detection strategy in high-risk population. However, there was no direct impact of HPV/HIV co-infection reported on these biomarkers and required to be studied more especially in people living with HIV. Highlights ◦ An analysis revealed a significant occurrence of high-risk HPV genotypes, namely HPV16, 18, and 45, among women who had HIV. ◦ In comparison to HIV-negative women, HIV-positive women had a higher probability of experiencing persistent HPV infections and more severe cervical lesions. ◦ Significant correlations were seen between CD4 levels and the occurrence of high-risk HPV infections, suggesting the involvement of immunosuppression in the persistence of HPV. ◦ Cervical cancer biomarkers reported across various studies were p16INK4a and Ki-67, despite these biomarkers reported there was no established direct impact of HPV/HIV co-infection to indicate aggressive disease development. ◦ The results suggest the need for implementation of focused screening and vaccination programs for cervical cancer in populations at high risk, particularly among women who are HIV-positive.

Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)—proteins that associate with RNA but lack known RNA-binding domains (RBDs). The vast majority of ucRBPs have uncharacterized RNA-binding specificities. We analyzed 492 human ucRBPs for intrinsic RNA-binding in vitro and identified 23 that bind specific RNA sequences. Most (17/23), including 8 ribosomal proteins, were previously associated with RNA-related function. We identified the RBDs responsible for sequence-specific RNA-binding for several of these 23 ucRBPs and surveyed whether corresponding domains from homologous proteins also display RNA sequence specificity. CCHC-zf domains from seven human proteins recognized specific RNA motifs, indicating that this is a major class of RBD. For Nudix, HABP4, TPR, RanBP2-zf, and L7Ae domains, however, only isolated members or closely related homologs yielded motifs, consistent with RNA-binding as a derived function. The lack of sequence specificity for most ucRBPs is striking, and we suggest that many may function analogously to chromatin factors, which often crosslink efficiently to cellular DNA, presumably via indirect recruitment. Finally, we show that ucRBPs tend to be highly abundant proteins and suggest their identification in RNA interactome capture studies could also result from weak nonspecific interactions with RNA.

Malaria remains a significant and worldwide health threat with increasing resistance to current treatments, stimulating the demand for innovative approaches in pursuing drug discovery. This systematic review integrates the progress made from 2014 through 2024 regarding molecular methods like gene expression profiling, molecular docking and machine learning to understand the biology of and identify new drug targets and compounds, focusing on herbal remedies and computational methods. Several studies were found using a PRISMA-guided search of PubMed, Scopus and Web of Science (64 studies found). The data extracted were gene expression outcomes, docking affinities, ML models and experimental validations (in vitro/in vivo). Molecular docking emerged as the dominant technique (32.37%), followed by in vitro antiplasmodial assays (14.39%), ADMET profiling (10.79%) and gene expression studies (3.60%). RNA-seq analysis revealed key host and parasite genes modulated by herbal treatments, including those involved in apoptosis and inflammation. Notably, compounds like isorhamnetin and myricetin 3-O-glucoside showed exceptionally high binding affinities to and lactate dehydrogenase (PfLDH) (ΔG < -13 kcal/mol). ML models like random forest and support vector machine (SVM) exhibited high predictive results (AUC value up to 0.87) for bioactivity and resistance patterns that showed flavonoids (quercetin) and terpenoids (eugenol) as good candidates. Pathways that are often attacked are haemoglobin degradation, glycolysis, pyrimidine metabolism and protein synthesis. Multiomics, docking and ML integration improve the target identification and prioritise the compounds. This review illustrates the great potential of molecular techniques for the development of drugs against antimalarial helicases that are not resistant to drug therapy. However, in vivo data holes and methodology inconsistency limit clinical translation. Future work should include standardisation of protocols and studies of synergistic combinations of phytochemicals.

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector–based assay.

HIV remains a major global health challenge with antiretroviral therapy (ART) effectively suppressing viral replication. However traditional ART does not eliminate viral reservoirs and is limited by systemic toxicity, long-term adherence burdens, and incomplete tissue penetration. These limitations highlight an important scientific problem in the inability of conventional ART to achieve durable remission or cure. Nanoparticle-mediated drug delivery systems have emerged as a transformative approach to address these limitations by improving drug solubility, stability, and targeted delivery to infected cells and viral sanctuaries such as the brain, lymphoid organs, and gastrointestinal mucosa. Different nanocarrier platforms including liposomes, polymeric nanoparticles, dendrimers, and lipid-based vesicles enable both passive and active targeting strategies. Functionalization with ligands such as antibodies, peptides, aptamers, and sugar moieties enhance cellular uptake, reduces off-target effects, and optimizes pharmacokinetics and biodistribution. Controlled-release formulations extend drug half-life and reduce dosing frequency, supporting long-acting regimens. Beyond drug delivery, nanoparticles also facilitate immunomodulatory therapies, therapeutic vaccines, and advanced gene-editing technologies such as CRISPR–Cas9. The convergence of nanotechnology, mRNA platforms, and artificial intelligence-driven drug development represents a paradigm shift toward individualized and precision HIV treatment. Despite these advances, significant translational challenges remain, including nanotoxicity, long-term safety, large-scale GMP manufacturing, regulatory barriers, and cost-effectiveness. Addressing these barriers is essential to unlock the full potential of nanoparticle-based strategies and translate them into equitable and sustainable clinical solutions.HighlightsThis review synthesizes evidence on nanoparticle-mediated antiretroviral delivery, focusing on pharmacokinetics, biodistribution, and viral reservoir targeting.Lipid- and polymer-based nanoparticles demonstrate measurable improvements in lymphoid tissue penetration and sustained plasma concentrations in preclinical models.Long-acting nanosuspensions of cabotegravir and rilpivirine provide clinical proof-of-concept for bi-monthly injectable HIV therapy.Emerging nanoplatforms enable integration with RNA therapeutics, immunomodulators, and CRISPR-based gene editing for future personalized interventions.Key translational challenges include nanotoxicity, GMP-scale manufacturing, regulatory frameworks, and cost-effectiveness, particularly in resource-limited settings.

Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4 + and CD8 + T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection. Immunocompromised individuals are predisposed to severe SARS-CoV-2 infection, with transplant recipients typically displaying impaired immune response to pathogens, due to typical life-long immunosuppressive treatment. In this work, the authors evaluate the immune response to Omicron subvariants BA.1 and BA.2 in organ transplant recipients across a diverse clinical spectrum.

This present study carried out a systematic review and meta-analysis of peptide nanoparticles in diabetes management for improved patient outcomes from 2014 to 2024. Different electronic databases, including PubMed, Scopus, Web of Science, ResearchGate, Google Scholar, and the Cochrane Library, were searched for relevant literature using Medical Subject Headings (MeSH) and boolean operators. A total of 317 articles were obtained and include PUBMED (39), Scopus (215), ResearchGate (30), Google Scholar (25), and Cochrane Library (8). From these, 186 duplicate entries were eliminated, while 76 articles were dismissed for some reasons. After scanning the titles, abstracts, and contents of the remaining 55 articles for relevance, 22 articles were eliminated. After a full-text screening using inclusion/exclusion criteria, an additional 11 articles were discarded, while 4 were excluded during the data extraction phase. In the end, seven (7) publications were considered relevant based on the eligibility criteria, representing 2.22%. Results showed that sequential exclusion of the studies did not have a significant impact on the effects of peptide nanoparticles on glucose control, insulin delivery, bioavailability, efficacy, safety, and patient outcomes in diabetes management. Also, peptide nanoparticles had positive improvement on glycemic control, insulin levels, glycated hemoglobin (HbA1C) levels, and overall patient outcomes. The study concludes that peptide nanoparticles harbour the potential to improve diabetes management through enhanced glucose control, insulin delivery, and patient outcomes. However, there is a significant gap in knowledge. Further research is required to understand the long-term safety and efficacy of many of the enlisted nanoparticles. Additionally, future studies should explore a wider range of peptides and proteins for encapsulation, develop delivery systems for larger and conformationally diverse molecules, and improve the oral bioavailability of encapsulated therapeutics. Long-term clinical trials are needed to validate this approach in humans and elucidate the underlying mechanisms for optimal treatment design. If these knowledge gaps are addressed, peptide nanoparticles will unavoidably become a powerful tool for effective management of diabetes along with traditional methods.HighlightsThe study performed a systematic review and meta-analysis on the use of peptide nanoparticles in diabetes management for the past decade, from 2014 to 2024.The study adopted PRISMA guidelines and PICOS framework in addressing the research questions. The results showed that the use of peptide nanoparticles was associated with improved glycemic control, insulin levels, reduced HbA1C, and overall patient outcomes in diabetes management.The study identified various types of peptide nanoparticles, including silica-based, polymeric, liposomes, dendrimers, inorganic, and carbon-based nanomaterials, that have been used for diabetes management.The study highlights the need for further research to fully understand the long-term effects, safety, and optimal dosage of peptide nanoparticles for diabetes management.

Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986–987) mutation present in other COVID-19 vaccines. The aim of the study was to evaluate safety, tolerability, and immunogenicity of PTX-COVID19-B vaccine in healthy seronegative adults 18–64 years old. The trial design was observer-blinded, randomized, placebo-controlled, and tested ascending doses of 16-µg, 40-µg, or 100-µg in a total of 60 subjects who received two intramuscular doses, 4 weeks apart. Participants were monitored for solicited and unsolicited adverse events after vaccination and were provided with a Diary Card and thermometer to report any reactogenicity during the trial. Blood samples were collected on baseline, days 8, 28, 42, 90, and 180 for serum analysis of total IgG anti-receptor binding domain (RBD)/Spike titers by ELISA, and neutralizing antibody titers by pseudovirus assay. Titers in BAU/mL were reported as geometric mean and 95% CI per cohort. After vaccination, few solicited adverse events were observed and were mild to moderate and self-resolved within 48 h. The most common solicited local and systemic adverse event was pain at the injection site, and headache, respectively. Seroconversion was observed in all vaccinated participants, who showed high antibody titers against RBD, Spike, and neutralizing activity against the Wuhan strain. Neutralizing antibody titers were also detected against Alpha, Beta, and Delta variants of concerns in a dose dependent manner. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-µg dose showed fewer adverse reactions than the 100-µg dose, and therefore was selected for a Phase 2 trial, which is currently ongoing. Clinical Trial Registration number: NCT04765436 (21/02/2021). ( https://clinicaltrials.gov/ct2/show/NCT04765436 ).