Wanna Chaijaroenkul

Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota–gut–brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, prebiotics, dietary indices, and botanicals, in alleviating insomnia, restoring circadian rhythms, and modulating neurochemical markers. Methods: In strict accordance with PRISMA 2020 guidelines, we searched PubMed, ScienceDirect, Scopus, and The Cochrane Library for English language studies published from inception to March 31, 2026. Eligibility was restricted to studies with rigorously controlled designs, specifically randomized controlled trials (RCTs) and controlled in vivo animal studies. Interventions had to target the gut microbiota, with primary outcomes measuring sleep quality (subjective or objective) or sleep-related neurochemical markers. We excluded uncontrolled, single-arm, or observational designs; in vitro studies; non-original research; and studies involving subjects with severe medical or psychiatric comorbidities (e.g., cancer, ADHD, severe psychiatric disorders) to prevent confounding variables, though mild-to-moderate anxiety and depression were permitted. Risk of bias was assessed using the Cochrane RoB 2.0 and SYRCLE tools. Due to significant methodological heterogeneity, a narrative synthesis stratified by intervention and population was conducted. This review was not registered in PROSPERO. Results: A total of 56 studies (33 humans, 23 animals) met the inclusion criteria. Taxonomic nomenclature was updated to reflect 2020 reclassifications (e.g., Lactiplantibacillus plantarum). In human trials, interventions significantly improved subjective sleep metrics (PSQI, ISI). Recent additions demonstrated the efficacy of the Dietary Index for Gut Microbiota (DI-GM) and the improvement in N3 sleep latency by yeast mannan. Furthermore, whole-food patterns (e.g., the MIND diet) and Traditional Chinese Medicine (TCM) decoctions successfully enriched beneficial taxa, such as Bacteroides coprophilus, and increased short-chain fatty acid (SCFA) production. Animal models demonstrated that “psychobiotic” strains (Bifidobacterium breve, Lacticaseibacillus paracasei), prebiotics (GOS/PDX), and TCM formulas effectively restored GABA/5-HT profiles, lowered morning cortisol, and facilitated REM rebound in PCPA-induced models, while also consolidating non-rapid eye movement (NREM) sleep and downregulating clock genes (Per1/Per2). Conclusions: Psychobiotics, prebiotics, and botanicals represent a highly viable non-pharmacological strategy for treating insomnia. However, current evidence is constrained by a heavy reliance on subjective human questionnaires, short follow-up durations limiting insight into long-term stability, and a substantial translational gap between mechanistic rodent models and human clinical outcomes.

Atractylodes lancea (AL) has been shown to be a promising candidate for the treatment of cholangiocarcinoma (CCA). The study explored the potential of atractylodin (AT) and β-eudesmol (BE) to chemosensitize the effects of standard chemotherapeutics in CCA. The cytotoxicities of AT and BE on CL6, HuCCT1, and HuH28 when used in combination with 5-fluorouracil (5FU), gemcitabine (GEM), and cisplatin (Cis) were assessed by MTT assay. The modulatory effects of both compounds on mRNA expression of the reuptake and efflux transporters were determined by real-time PCR. The FIC (Fractional Inhibitory Concentration) indices indicated synergistic interactions (AT-5FU in all cell lines and BE-5FU in HuH28) and antagonistic interactions (BE-Cis in all cell lines and AT-Cis or AT-GEM in HuCCT1). The synergistic interactions observed with the AT-5FU and BE-5FU combinations were well correlated with the significant upregulation of the mRNA expression of the reuptake transporter genes hENT1 (2.64-fold) and hOCT3 (5.02-fold) and the significant downregulation of the mRNA expression of the efflux transporter gene ABCC2 (0.33-fold). AT and BE, when purified or present as significant components in AL, may benefit CCA treatment when used as adjunct therapy to standard chemotherapeutic drugs, particularly 5FU. The mechanism of synergistic activity may, at least in part, involve modulation of transporter gene expression and activity.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy in which numerous biomarker candidates have been reported, yet few progress to clinical use. Beyond biological complexity, this low translational yield reflects the lack of systematic criteria for prioritizing biomarkers during the discovery stage. In particular, tumor-derived signals identified in tissue often fail to persist in clinically accessible biofluids, as cross-compartment signal behavior is rarely evaluated explicitly. Methods: We developed an extracellular vesicle (EV)-guided, multi-compartment proof-of-concept framework to assess biomarker robustness and translatability early in discovery. EV proteomes from three biologically distinct CCA cell lines and a normal cholangiocyte were analyzed using multivariate and machine-learning-assisted approaches to identify conserved EV-associated features. These were integrated with public transcriptomic, epigenetic, copy-number, promoter usage, and miRNA regulatory data. Tissue relevance was assessed using TCGA/GTEx RNA-seq datasets, and exploratory signal behavior was examined in pooled serum- and urine-derived EVs from CCA patients and controls. Results: EV proteomics revealed marked molecular heterogeneity across CCA models but identified a small subset of conserved EV-associated proteins. SERPINF2 was used as a representative example, showing consistently reduced EV-associated abundance across all CCA models with coordinated regulation across multiple molecular layers. SERPINF2 expression was independent of patient sex and tumor stage and clearly distinguished tumor from normal bile duct tissue. Exploratory biofluid analyses demonstrated compartment-dependent signal behavior, with SERPINF2 depletion detectable in urine-derived EVs but not in serum-derived EVs. Conclusions: Rather than validating a single biomarker, this study presents an EV-guided, multi-compartment framework for prioritizing biomarker candidates at the discovery stage. By explicitly accounting for tumor heterogeneity and compartment-specific signal preservation, this proof-of-concept approach provides a practical decision-support strategy for identifying biomarkers with greater translational potential in heterogeneous cancers such as CCA.

Microalbuminemia, characterized by a urinary albumin concentration between 20 and 200 mg/L, is a critical marker in assessing the risk of chronic kidney disease (CKD), diabetic nephropathy, and various other chronic conditions. Previously, we developed and validated the MyACR point-of-care (PoC) device, which facilitates the monitoring of CKD progression through real-time data transmission, thus enhancing patient management. This device utilizes a spectrophotometric dye-binding assay to measure albumin and creatinine concentrations in urine samples, providing an albumin-to-creatinine ratio (ACR) result. In the present study, we introduced a refined version of the PoC device, MyμAlbumin, designed to offer a simple, accurate, specific, sensitive, and rapid method for detecting microalbumin in urine as an early indicator of CKD and related diseases. The measurement is based on a specific immunoturbidimetric assay in a microcuvette, using a total solution volume of 125 µL (n = 5 for each validation test). The MyμAlbumin device demonstrated excellent performance, achieving high accuracy (%DMV ≤ 4.67) and precision (%CV < 5) and a strong correlation (R² > 0.995) with laboratory spectrophotometry (dye-binding assay) and reference hospital-based immunoturbidimetric assay. Its high sensitivity (LOQ = 5 mg/L) positions MyμAlbumin as a highly viable and cost-effective tool for clinical use. Additionally, the device supports real-time, seamless data transmission, making it ideal for integration into remote healthcare settings.

Chronic kidney disease (CKD) continues to pose a critical global health challenge, making ongoing monitoring vital for effective management and preventing its progression to end-stage renal disease. The urinary albumin-to-creatinine ratio (uACR) stands out as a reliable biomarker. MyACR was developed and validated as a novel point-of-care (POC) device for identifying and monitoring the progress of CKD. MyACR device operates using a colorimetric-based spectroscopy to quantify albumin and creatinine levels at 625 nm and 515 nm, respectively. Calculated uACR values were compared with results from the reference turbidimetry method using a dataset of 103 random urine samples from patients at high risk of advanced CKD. The device showed excellent performance in detecting severe nephropathy, with sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively. The PPV (positive predictive value) was 100%, indicating perfect identification of patients with severe nephropathy (uACR > 300 mg/g creatinine). The NPV (negative predictive value) was 100%, suggesting a strong ability to rule out severe nephropathy, though a small risk of false negatives remained. Bland–Altman analysis confirmed a high level of agreement, with 96.11% (for all data) and 95.87% (for uACR > 300 mg/g creatinine) of MyACR measurements falling within the 95% confidence interval (−27 to +19). Correlation analysis revealed a significant alignment between MyACR and the reference method (r² 0.9720 to 0.9836). The ROC analysis suggested that combining uACR with the estimated glomerular filtration rate (eGFR) demonstrated strong predictive performance, yielding an area under the curve (AUC) of 0.933 (95% CI: 0.86–1.0). In conclusion, the MyACR device is a robust, affordable, and user-friendly tool for detecting nephropathy, showing performance comparable to the reference method. Its portability and cost-effectiveness make it particularly suitable for use in low-resource environments. Additionally, integrating uACR with eGFR enhances prognostic capabilities, offering a comprehensive approach to assessing kidney function and predicting CKD progression.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world’s population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device, MyACR, for uACR measurement, intended for use in community healthcare to screen for the risk and monitor the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25 °C) for 30 min before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (0–60 mg/L and 0–2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (R²) of >0.997. Good accuracy (% deviation of mean value (DMV) ≤ 5.42%) and precision (% coefficients of variation (CV) ≤ 12.69%) were observed from both the intra- and inter-day assays for the determination of albumin and creatinine using MyACR. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined using MyACR and a laboratory spectrophotometer were 5 mg/L and 0.25 mg/dL, respectively, using 37.5 μL urine spiked samples (n = 5). The device was well-applied with clinical samples from 20 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.48 (−17.05 to 21.64)%, with a high correlation coefficient (R² > 0.98). In conclusion, MyACR showed satisfactory test performance in terms of accuracy, reproducibility, and sensitivity. Cost-effectiveness and improvement in clinical decision making need to be proven in future multisite community and home studies.

Plasmodium vivax (Pv) accounts for over 50% of malaria cases in Latin America and Asia. Despite a significant reduction in Pv transmission in Thailand, the parasite remains endemic to the border areas. This study aimed to investigate the genetic diversity of the parasites and the host factors, as well as their relation to parasite density in Pvisolates, along the Thai–Myanmar border. Genetic variations in Pv markers, specifically the ookinete surface protein Pvs25, and host genes, including Toll-like receptor 6 (TLR6), TLR9, TIR Domain-containing adaptor protein (TIRAP), Toll-interacting protein (TOLLIP), Duffy antigen receptor for chemokines (DARC), and intercellular adhesion molecule 1 (ICAM-1), were investigated using polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). A total of 548 PCR-positive Pv samples collected from Tak and Kanchanaburi provinces during two periods (2006–2007 and 2014–2016) were included in the study. Pvs25 exhibited four haplotypes, with H1 (EGTKV) being the most prevalent in both provinces. Kanchanaburi isolates exhibited greater genetic diversity than Tak isolates. No significant deviations from neutrality were observed for Pvs25 in either area. ICAM-1 and TOLLIP s3750920 heterozygous carriers had greater median parasite densities than homozygous mutants. The TLR9 rs187084 T genotype had a significantly higher parasite density than the non-T genotype. The findings underscore the significant association between the rs3750920 C/T, rs5498 A/G, and rs187084 T genotypes and high parasite density in patients infected with Pv, highlighting their potentially critical role in malaria susceptibility.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world's population. Monitoring urine albumin and creatinine ratio (µACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device - MYμALBUMIN that community healthcare professionals can use in resource-limited facilities and by patients in their own homes for screening the risk and monitoring the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe’assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25oC) for 30 minutes before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (2-60 mg/L and 0.25-2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (r2) of > 0.999. Good accuracy (%DMV < + 2.88%) and precision (%CV < 3.0%) were observed from both the intra- or interday assays for the determination of albumin and creatinine by MYµALBUMIN. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined by MYµALBUMIN and laboratory spectrophotometer were 2 mg/L and 0.1 mg/dL, respectively, using 37.5 μL urine samples. The device was well applied with clinical samples from 13 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.18 (-10.11 to 14.12)%, with a high correlation coefficient (r2 >0.99). In conclusion, MYμALBUMIN showed satisfactory test performance in terms of accuracy, reproducibility, sensitivity, and specificity. The device would have significant economic benefits besides obviously improving clinical decision-making processes.

Plasmodium vivax malaria cases remain high along the Thai-Myanmar and Thai-Cambodia borders. Plasmodium vivax circumsporozoite protein (pvcsp) and Plasmodium vivax ookinete surface protein (pvs25) genes are promising molecular markers of the genetic diversity of P. vivax. This study investigated the genetic diversity of pvcsp and pvs25 in P. vivax isolates collected from the Thai-Myanmar border. The DNA samples were amplified, and the genotypes were analyzed by PCR–RFLP and DNA sequencing. Pvcsp genotypes, VK210, VK247, and mixed types, were found in 203 (91.9%), 15 (6.8%), and 3 (1.3%) of the isolates, respectively. Twenty-four allelic variants were observed, of which a high prevalence of VK210E and VK247E were reported. Two pvcsp variants, VK210C and VK210M showed significantly higher parasite density (46,234 (1154–144,000) vs. 25,606 (1373–68,878), respectively). The genetic diversity of pvcsp along the Thai-Myanmar border during 2002–2015 showed dynamic changes with both positive and negative selection. The frequency and distribution of pvcsp pattern might be changed over time and might be other factors contributing to gene selection. Three amino acid substitutions of pvs25, i.e., E97Q, I130T, and Q131K, were investigated with frequencies of 10 (4.5%), 221 (100%), and 204 (92.3%) isolates, respectively. There was no association between parasite density and pvs25 polymorphisms. The frequency of pvs25 polymorphism was similar to that previously reported, with the absence of random mutation. In conclusion, the genetic variation of pvcsp was changed over times whereas the genetic diversity of pvs25 was limited; these variations would be helpful for further vaccine development against P. vivax malaria.

High levels of genetic variants of Plasmodium vivax have previously been reported in Thailand. Circumsporozoite surface protein (CSP), merozoite surface protein (MSP), and microsatellite markers were used to determine the genetic polymorphisms of P. vivax. This study aimed to investigate the molecular epidemiology of P. vivax populations at the Thai–Myanmar border by genotyping the PvCSP, PvMSP-3α, and PvMSP-3β genes. Four hundred and forty P. vivax clinical isolates were collected from the Mae Sot and Sai Yok districts from 2006–2007 and 2014–2016. Polymerase chain reaction with restriction fragment length polymorphism (RFLP) was used to investigate the genetic polymorphisms of the target genes. Based on PCR band size variations, 14 different PvCSP alleles were identified: eight for VK210 and six for VK247. The VK210 genotype was the dominant variant during both sample collection periods. Based on PCR genotyping, three distinct types (A, B, and C) for both PvMSP-3α and PvMSP-3β were observed. Following RFLP, 28 and 14 allelic variants of PvMSP-3α and 36 and 20 allelic variants of PvMSP-3β with varying frequencies were identified during the first and second periods, respectively. High genetic variants of PvMSP-3 and PvCSP were found in the study area. PvMSP-3β exhibited a higher level of genetic diversity and multiple-genotype infection versus PvMSP-3α.