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Japanese encephalitis virus (JEV) is a mosquito-borne pathogen that causes severe neurologic disease. Its endemicity in Asia has prompted its inclusion in nationwide immunization programs. However, the Philippines, which is also endemic for related viruses like dengue (DENV), has not yet adopted this practice. Vaccine hesitancy is a major challenge, exacerbated by concerns over cross-reactive antibodies that may enhance viral infection. This study aimed to determine whether IMOJEV vaccination would induce cross-neutralizing or enhancing antibodies against DENV. Pre- and one-month post-vaccination samples from IMOJEV-vaccinated Filipino children (9-24 months old) were analyzed. A reporter virus particle (RVP)-based neutralization assay against JEV showed neutralization in 28/29 subjects post-vaccination. Presence of DENV2-reactive antibodies was measured via DENV2 VLP ELISA, which revealed increased DENV2 binding reactivity post-vaccination. Pre-vaccination DENV2 binding reactivity also had no significant correlation with the JEV vaccine response. RVP-based neutralization and enhancement assays against DENV2 showed that there was no significant change in neutralizing or enhancing antibody activity against DENV2 after JEV vaccination. This study shows that IMOJEV vaccination elicited a JEV neutralizing response in 97% of vaccinees and that the magnitude of JEV neutralizing titers post-vaccination was not associated with pre-existing binding antibodies to DENV2. Further, while live JEV vaccination increases DENV2-binding antibodies, this cross-reactivity does not lead to DENV2 enhancement. These findings contribute to a better understanding of the orthoflavivirus antibody response following immunization and the influence of pre-existing heterologous orthoflavivirus antibodies. This could guide vaccination strategies, especially in orthoflavivirus-endemic regions.

The unregulated and inappropriate use of antibiotics triggered the rapid spread of antimicrobial resistance in pathogenic microorganisms such as Pseudomonas aeruginosa . Antimicrobial peptides (AMPs) require investigations of their remarkable bioactivities and unique microbicidal mechanisms as potential replacement treatments for conventional antibiotics. Specifically, a naturally occurring antimicrobial dodecapeptide named Histatin 8 (HS8), from the Histatin family, has weak to moderate antimicrobial activities but is a promising bioactive molecule. In this study, three well-represented HS8-derived peptides with potential in silico bioactive propensities namely HS8-1 (Tyr12Phe), HS8-2 (Ser8Phe and Tyr12Phe), and HS8-3 (Gly11Phe) were explored. Results showed that HS8-1 was a significantly more active AMP than HS8-2 and HS8-3, displaying 3.0-fold and 3.56-fold decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, respectively, against wild-type P. aeruginosa . Furthermore, HS8-1 and HS8-2 displayed the lowest MIC and MBC values against the antibiotic-resistant P. aeruginosa . Both HS8-2 and HS8-1 are the more active peptides showing inhibitory activities against wild-type and antibiotic-resistant P. aeruginosa biofilms in vitro, respectively. HS8-1 and HS8-2, at their MICs, can both primarily induce surface roughening and corrugation suggesting possible disruptive effects on the P. aeruginosa membrane reflecting antimicrobial action. HS8-1 lyses human red blood cells (RBCs) in vitro at concentrations 250 µg/mL and below, suggesting it to be the least hemolytic peptide compared to HS8-2 and HS8-3 which strongly lyse RBCs at relatively lower concentrations. Overall, the results imply that the HS8-derived peptide bioactivities can be enhanced by site-specific phenylalanine (Phe) substitutions against P. aeruginosa .

miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, CHD 25, ENI 25) using next-generation sequencing (NGS). Overall miRNA profiles were consonant in serum and HBsAg-particles but significantly different according to the presence of hepatitis independently of Hepatitis D Virus (HDV)-co-infection. Stringent (Bonferroni Correction < 0.001) differential expression analysis showed 39 miRNAs upregulated in CHB vs. ENI and 31 of them also in CHD vs. ENI. miRNA profiles were coincident in CHB and CHD with only miR-200a-3p upregulated in CHB. Three miRNAs (miR-625-3p, miR-142-5p, and miR-223-3p) involved in immune response were upregulated in ENI. All 3 hepatocellular miRNAs of MiR-B-Index (miR-122-5p, miR-99a-5p, miR-192-5p) were overexpressed in both CHB and CHD patients. In conclusion, CHD and CHB patients showed highly similar serum miRNA profiling that was significantly different from that of individuals with HBeAg-negative infection and without liver disease.

Saliva has been demonstrated as feasible alternative to naso-oropharyngeal swab (NOS) for SARS-CoV-2 detection through reverse transcription quantitative/real-time polymerase chain reaction (RT-qPCR). This study compared the diagnostic agreement of conventional NOS, saliva with RNA extraction (SE) and saliva without RNA extraction (SalivaDirect) processing for RT-qPCR in identifying SARS-CoV-2. All techniques were also compared, as separate index tests, to a composite reference standard (CRS) where positive and negative results were defined as SARS-CoV-2 detection in either one or no sample, respectively. Of 517 paired samples, SARS-CoV-2 was detected in 150 (29.01%) NOS and 151 (29.21%) saliva specimens. The saliva-based tests were noted to have a sensitivity, specificity and accuracy (95% confidence interval) of 92.67% (87.26%, 96.28%), 97.55% (95.40%, 98.87%) and 96.13% (94.09%, 97.62%), respectively, for SE RT-qPCR and 91.33% (85.64%, 95.30%), 98.91% (97.23%, 99.70%) and 96.71% (94.79%, 98.07%), respectively, for SalivaDirect RT-qPCR compared to NOS RT-qPCR. Compared to CRS, all platforms demonstrated statistically similar diagnostic performance. These findings suggest that both conventional and streamlined saliva RT-qPCR are at least non-inferior to conventional NOS RT-qPCR in detecting SARS-CoV-2.

Chorion trophoblasts (CTCs) and immune cell-enriched decidua (DECs) comprise the maternal-fetal membrane interface called the chorio-decidual interface (CDi) which constantly gets exposed to maternal stressors without leading to labor activation. This study explored how CTCs act as a barrier at CDi. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating immune homeostasis were also investigated. The CDi was recreated in a two-chamber microfluidic device (CDi-on-chip) with an outer chamber of primary DECs and immune cell line-derived innate immune cells and an inner chamber of wild-type or PGRMC2 or HLA-G knockout immortalized CTCs. To mimic maternal insults, DECs were treated with lipopolysaccharide, poly(I:C), or oxidative stress inducer cigarette smoke extract. Expression levels of inflammation and immunity genes via targeted RNA sequencing, production of soluble mediators, and immune cell migration into CTCs were determined. In CDi-on-chip, decidua and immune cells became inflammatory in response to insults while CTCs were refractory, highlighting their barrier function. HLA-G and PGRMC2 are found to be vital to immune homeostasis at the CDi, with PGRMC2 serving as an upstream regulator of inflammation, HLA-G expression, and mesenchymal-epithelial transition, and HLA-G serving as a frontline immunomodulatory molecule, thus preventing fetal membrane compromise. An organ-on-chip model of the maternal-fetal membrane interface reveals that HLA-G and PGRMC2 produced by chorion trophoblasts modulate inflammation, thus serving as immunological barrier to prevent membrane compromise.

Background Hypertension is a major health problem in the Philippines, being the second leading disease and the second leading factor driving the most death and disability in the country. Despite efforts made toward increasing awareness, improving availability of medications, and strengthening patient adherence, more than 7 in every 10 hypertensive Filipinos still have uncontrolled hypertension. Main body In the recent years, the role of gut microbiota in hypertension has been highlighted, with studies showing alterations in the gut microbiota of hypertensive individuals and its positive effect on the pharmacokinetics of some antihypertensive drugs. Conclusions These findings show how gut microbiota can be an important but possibly overlooked consideration in the management of hypertension in the Philippines. Clinicians might benefit from maximizing the relationship between gut microbiota and hypertension to achieve good BP control and ultimately address the burden of uncontrolled hypertension in the country.

Flaviviruses include virus species that are major public health threats worldwide. To determine the immunity landscape of these viruses, seroprevalence studies are often performed using IgG ELISA, which is a simple and rapid alternative to the virus neutralization test. In this review, we aim to describe the trends in flavivirus IgG ELISA-based serosurveys. A systematic literature review using six databases was performed to collate cohort and cross-sectional studies performed on the general population. A total of 204 studies were included in this review. The results show that most studies were performed on dengue virus (DENV), whereas Japanese Encephalitis Virus (JEV) was the least studied. For geographic distribution, serosurveys followed known disease prevalence. Temporally, the number of serosurveys increased after outbreaks and epidemics except for JEV, for which studies were performed to demonstrate the effectiveness of vaccination campaigns. Commercial kits were more commonly used than in-house assays for DENV, West Nile Virus (WNV), and Zika virus (ZIKV). Overall, most studies employed an indirect ELISA format, and the choice of antigens varied per virus. This review shows that flavivirus epidemiology is related to the regional and temporal distribution of serosurveys. It also highlights that endemicity, cross-reactivities, and kit availabilities affect assay choice in serosurveys.

Human immunodeficiency virus (HIV) infection continues to present a global health issue. Recent studies have explored the potential role of the gut microbiome in HIV infection for novel therapeutic approaches. We investigated the gut microbiome composition of people living with HIV (PLHIV) in the Asia–Pacific region. This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. An electronic search was conducted in the PubMed/MEDLINE, Scopus, and ScienceDirect databases using keywords such as “HIV”, “PLHIV”, “AIDS”, “gut microbiome”, “gut dysbiosis”, and “metagenomics”. Only peer-reviewed and full-text studies published in English were included. A total of 15 studies from the Asia–Pacific region were included for analysis. Compared to healthy controls, PLHIV showed an increased abundance of Proteobacteria and its genera, which may be considered pathobionts, and decreased abundances of Bacteroidetes and several genera under Firmicutes with known short-chain fatty acid and immunoregulatory activities. Predominant taxa such as Ruminococcaceae and Prevotellaceae were also associated with clinical factors such as CD4 count, the CD4/CD8 ratio, and inflammatory cytokines. This review highlights gut microbiome changes among PLHIV in the Asia–Pacific region, indicating potential bacterial signatures for prognostication. The partial restoration of the microbiome toward beneficial taxa may ensure the long-term success of treatment, promoting immune recovery while maintaining viral load suppression.

ABSTRACT Here, we aim to understand the condition of the gut microbiome of Filipino adults in relation to their diet and metabolic status. Compared to rural Albay (n = 67), the gut microbiome of subjects living in urban Manila (n = 25) was more colonized by the order Clostridiales, which was negatively correlated with host carbohydrate consumption. Principal component analysis using the genus composition of the 92 total subjects indicated four microbiome types: one type driven by Prevotella, which was associated with high rice consumption and mainly consisted of healthy Albay subjects, one Clostridiales-driven group containing a number of type 2 diabetes mellitus (T2D) subjects from both Manila and Albay who showed lower butyrate levels in association with a decrease in Mediterraneibacter faecis, and the other two types showing dysbiosis-like microbiomes with Lactobacillus and Bifidobacterium overgrowth, with a high ratio of T2D and obese subjects. Multivariate logistic regression analysis suggested high dietary energy intake, and two Veillonellaeae genera, Dialister and Megasphaera, as T2D risk factors, while Prevotella and M. faecis as anti-T2D factors. In conclusion, low-carbohydrate diets restructured the Prevotella-driven gut microbiome, which may predispose Filipino people with high energy diet to T2D. Urban-type low-carbohydrate diets restructured the Prevotella-driven gut microbiome, which may predispose Filipino people with high energy diet to type 2 diabetes mellitus.

HPV infection is one of the most studied risk factors in cervical cancer—the second most common cancer site and cause of death due to cancer in the Philippines. However, there is a lack of population-based epidemiological data on cervical HPV infection in the Philippines. Local reports on co-infections with other lower genital tract pathogens, commonly reported globally, are also lacking, which emphasizes the need to increase efforts in targeting HPV prevalence, genotype, and distribution. Hence, we aim to determine the molecular epidemiology and natural history of HPV infection among reproductive-age Filipino women using a community-based prospective cohort design. Women from rural and urban centers will be screened until the target sample size of 110 HPV-positive women (55 from rural sites and 55 from urban sites) is reached. Cervical and vaginal swabs will be collected from all screened participants. For HPV-positive patients, HPV genotypes will be determined. One hundred ten healthy controls will be selected from previously screened volunteers. The cases and controls will comprise the multi-omics subset of participants and will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analyses of the vaginal swabs will also be performed at baseline, after 6 months, and after 12 months. The results of this study will update the prevalence and genotypic distribution of cervical HPV infection among Filipino women, determine whether the current vaccines used for HPV vaccination programs capture the most prevalent high-risk HPV genotypes in the country, and identify vaginal community state types and bacterial taxa associated with the natural history of cervical HPV infection. The results of this study will be used as the basis for developing a biomarker that can help predict the risk of developing persistent cervical HPV infection in Filipino women.