Background: Interleukin (IL)-1β is a proinflammatory cytokine that has a role in disease-related inflammation, including malaria. However, reports on the effect of IL-1β on malaria severity are inconsistent. Therefore, meta-analyses to compare differences in IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls were performed.Methods: The PRISMA standards were used to perform a systematic review and meta-analysis. A search of PubMed, Scopus, EMBASE and reference lists was conducted for articles providing data on IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls between January 1988 and March 2022, using a combination of search terms. The quality of all studies included in this review was determined using the Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. The evidence was synthesized quantitatively and qualitatively. The differences in IL-1 levels across participant groups were recounted narratively for qualitative synthesis. For quantitative synthesis, the mean difference in IL-1β levels across groups of participants was calculated using a random effects meta-analysis. The publication bias was assessed using funnel plots, Egger’s test and a contour-enhanced funnel plot.Results: A total of 1281 articles were discovered, and the 17 that satisfied the inclusion criteria were included for syntheses. The meta-analysis results using data from 555 cases of severe malaria and 1059 cases of uncomplicated malaria showed that severe malaria had a higher mean of IL-1β levels than uncomplicated malaria (P < 0.01, pooled mean difference: 1.92 pg/mL, 95% confidence interval: 0.60–3.25 pg/mL,I²: 90.41%, 6 studies). The meta-analysis results using data from 542 cases of uncomplicated malaria and 455 healthy controls showed no difference in mean IL-1β levels between the two groups (P = 0.07, pooled mean difference: 1.42 pg/mL, 95% confidence interval: − 0.1–2.94 pg/mL,I²: 98.93%, 6 studies).Conclusion: The results from the meta-analysis revealed that IL-1β levels were higher in patients with severe malaria than in patients with uncomplicated malaria; however, IL-1β levels were similar in patients with uncomplicated malaria and healthy controls. Based on the limitations of the number of studies included in the meta-analysis and high levels of heterogeneity, further studies are needed to conclude that differences in IL-1β levels can be useful for monitoring the malaria severity.

Although many studies have investigated the role of interleukin (IL)-12 cytokine in the pathogenesis of severe malaria, these studies were based on a limited number of participants, possibly affecting their outcomes. We analyzed the difference in IL-12 levels between patients with severe and uncomplicated malaria through a meta-analysis. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Interventions and was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Systematic literature searches were performed between 20 February and 2 March, 2022 in PubMed, Scopus, and Embase to identify studies reporting IL-12 levels in patients with severe and uncomplicated malaria. The quality of included studies was determined using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The pooled mean difference (MD) in IL-12 between patients with severe and uncomplicated malaria was estimated using the DerSimonian–Laird method for the random-effects model. Altogether, 1885 potentially relevant articles were identified, and 10 studies enrolling 654 patients with severe malaria and 626 patients with uncomplicated malaria were included in the meta-analysis. Patients with severe malaria had lower mean IL-12 levels than those with uncomplicated malaria (p = 0.01, MD: −33.62, 95% confidence interval [CI]: −58.79 to −8.45, I²: 99.29%, 10 studies). In conclusion, decreased IL-12 levels might significantly contribute to the development of severe malaria. As most published literature demonstrated the role of IL-12 in animal models, human studies are required to understand the mechanisms involved in low IL-12 levels in patients with severe malaria.

Background and Aim: Alzheimer’s disease (AD) poses a significant health-care challenge, often linked to cognitive decline caused by oxidative stress. This study investigated the potential neuroprotective effects of the Paederia foetida leaf extract (PFE) in rats that exhibited scopolamine-induced dementia mimicking AD. Materials and Methods: Forty-two male rats were treated with either donepezil (0.5 mg/kg) or PFE at doses of 250, 500, and 1000 mg/kg for 14 days before and 14 days after the beginning of Alzheimer’s-like symptoms after 14 consecutive days of scopolamine administration. Behavioral tests, including the open-field test for locomotor activity and the Morris water maze task for learning and memory assessment, were conducted. Neuronal cell counts and biochemical assays were performed to further analyze outcomes. Results: All groups exhibited normal locomotor activity. The scopolamine group displayed longer escape latency times, reduced time in the target quadrant, decreased number of surviving neurons, and increased malondialdehyde and decreased glutathione levels compared with the control group. However, pre-treatment with 1000 mg/kg PFE notably mitigated the neurotoxic effects of scopolamine. Conclusion: The neuroprotective properties of PFE are highlighted, suggesting its potential as a promising treatment strategy for AD. Keywords: Alzheimer’s disease, neuroprotection, oxidative stress, Paederia foetida, scopolamine.

Transforming growth factor-β (TGF-β) is important in the pathophysiology of malaria, but its role in acute and severe malaria is largely unknown. As a result, this study used a meta-analysis approach to investigate the difference in TGF-β levels between several groups of malaria patients and healthy controls. The systematic review protocol was registered at PROSPERO (ID: CRD42022318864). From inception to 7 March 2022, studies that reported TGF-β levels in patients with uncomplicated and healthy controls and patients with severe and uncomplicated malaria were searched in PubMed, Scopus and Embase. The assessment of the quality of the included studies was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Qualitative and quantitative syntheses were performed to narratively describe and quantitatively pool the mean difference (MD) in TGF-β levels between uncomplicated malaria and healthy controls, and between severe and uncomplicated malaria, using a random-effects model. A total of 1027 relevant articles were identified, and 13 studies were included for syntheses. The meta-analysis results show 233 patients with uncomplicated malaria and 239 healthy controls. Patients with uncomplicated malaria (233 cases) had lower mean TGF-β levels than healthy controls (239 cases; p < 0.01, pooled MD = −14.72 pg/mL, 95% confidence interval (95% CI) = −20.46 to 8.99 pg/mL, I² = 98.82%, seven studies). The meta-analysis found no difference in mean TGF-β levels between patients with severe malaria (367 cases) and patients with uncomplicated malaria (180 cases; p = 0.11, pooled MD = −6.07 pg/mL, 95% CI = −13.48 to 1.35 pg/mL, I² = 97.73%, six studies). The meta-analysis demonstrated decreased TGF-β levels in patients with uncomplicated malaria compared to healthy controls. In addition, no difference in TGF-β levels was found between patients with severe and uncomplicated malaria. More research is needed to determine whether TGF-β levels could be a candidate marker for malarial infection or disease severity.

Background and Aim: Keratitis is a serious ocular infection often caused by pathogenic micro-organisms such as Acanthamoeba spp. Among other harmful microbes, Acanthamoeba keratitis presents a particular challenge due to its resistance to conventional antimicrobial agents. Piper betle Linn., commonly known as betel leaf, has been traditionally used for its medicinal properties. This study aimed to assess the potential of the leaf ethanol extract of P. betle Linn. in the treatment of Acanthamoeba triangularis in monoculture and co-culture with two prevalent pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, associated with keratitis. Materials and Methods: Minimum inhibitory concentrations (MICs) of A. triangularis, S. aureus, and P. aeruginosa extracts in monoculture and coinfected conditions were examined. In addition, this study explored the potential of the extract in preventing Acanthamoeba adherence in both monoculture and co-culture environments. Scanning electron microscopy (SEM) analysis confirmed the impact of the extract on Acanthamoeba cell membranes, including acanthopodia. Furthermore, a time-kill kinetic assay was used to validate the amoebicidal activity of the extract against A. triangularis and the tested bacteria. Results: MICs for trophozoites, cysts, P. aeruginosa, and S. aureus in the monoculture were 0.25, 0.25, 0.51, and 0.128 mg/mL, respectively, whereas the MICs for Acanthamoeba coinfected with bacteria were higher than those in the monoculture. This extract inhibited the growth of A. triangularis trophozoites and cysts for up to 72 h. Moreover, P. betle extract effectively prevented the adherence of Acanthamoeba to contact lenses under monoculture conditions. SEM analysis confirmed that P. betle extract affects the cell membrane of Acanthamoeba, including Acanthopodia. In addition, the time-kill kinetic assay confirmed that the extract contained amoebicidal activity against A. triangularis, including the tested bacteria. Notably, S. aureus was more susceptible than A. triangularis and P. aeruginosa to P. betle extract treatment. Unexpectedly, our study revealed that S. aureus negatively affected A. triangularis in the co-culture after 3 days of incubation, whereas P. aeruginosa facilitated the growth of A. triangularis in the presence of the extract. Conclusion: This study provides compelling evidence of the anti-adhesive and anti-Acanthamoeba properties of P. betle leaf extract against A. triangularis under monoculture and co-culture conditions. The observed impact on Acanthamoeba cell membranes, coupled with the time-kill kinetic assay results, underscores the potential of P. betle leaf extract as a promising agent for combating Acanthamoeba-related infections in humans and animals. Keywords: Piper betle extract, Acanthamoeba triangularis, co-infection, keratitis, Pseudomonas aeruginosa, Staphylococcus aureus.