Cholangiocarcinoma (CCA) is a lethal cancer associated with chronic inflammation caused by Opisthorchis viverrini infection, with high prevalence in Thailand. Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor involved in inflammation, has recently been identified as an oncogenic factor in several malignancies. However, its role in CCA remains unclear. Here, we demonstrate that SLPI is significantly upregulated during CCA development in both human and hamster-induced tissues. Higher SLPI expression was correlated with poor patient survival based on bioinformatic analyses. SLPI was elevated in highly metastatic CCA cell lines and further inducible by IL-6 stimulation. Overexpression of SLPI enhanced tumorigenic properties, including proliferation, migration, invasion, and in vivo tumor growth. SLPI also increased the activity of matrix metalloproteinases (MMP-2 and MMP-9), promoting metastatic potential. While conditioned media from SLPI-overexpressing cells did not affect angiogenesis, these cells promoted vasculogenic mimicry, with increased expression of VEGFA and VE-cadherin, and decreased N-cadherin. These findings suggest that SLPI promotes cholangiocarcinoma progression through inflammation-associated and vasculogenic mechanisms, highlighting its potential as a candidate molecular target for therapeutic intervention.

Introduction Cholangiocarcinoma (CCA) is a highly metastatic bile duct cancer with the highest global incidence in Northeastern Thailand. Most patients are diagnosed at advanced stages, necessitating the identification of novel prognostic markers and therapeutic targets. High mobility group A1 (HMGA1) is a non-histone chromosomal protein that orchestrates the transcription of genes involved in tumor progression, and its overexpression has been implicated in multiple malignancies. Aims: This study aimed to investigate the clinical significance and oncogenic roles of HMGA1 in CCA progression. Methods HMGA1 expression was evaluated in a hamster CCA model and human CCA tissues using immunohistochemistry. The functional effects of HMGA1 on cell growth, migration, and invasion, along with the underlying molecular mechanisms were investigated in vitro using human CCA cell lines. Results HMGA1 upregulation was detected as an early event in the cholangiocarcinogenesis of a hamster model. In the human cohort (n = 81), high HMGA1 expression significantly correlated with histological type ( p =0.014), metastatic stage ( p =0.004) and shorter overall survival ( p =0.024). In vitro , siRNA-mediated suppression of HMGA1 remarkably inhibited cell proliferation. While HMGA1 silencing increased cleaved caspase-3, it resulted in only a modest increase in the apoptotic cells. Instead, this caspase activation was primarily associated with a marked reduction in cell migration and invasion through the modulation of epithelial-mesenchymal transition (EMT) markers, and cytoskeletal remodeling in a cell line-specific manner. Conclusions: These retrospective and preclinical findings suggest that HMGA1 is a critical driver of CCA progression and a valuable prognostic indicator. HMGA1 promotes neoplastic transformation and aggressiveness of CCA. Targeting HMGA1 may serve as a potential therapeutic strategy to attenuate CCA progression, warranting further clinical validation.

This work reports on the development of paper-based analytical devices (PADs) that eliminate micropipette usage during sample loading. The sample was loaded into the PADs by dipping into the urine samples that contain creatinine (Cre), a biomarker commonly used to assess kidney function. The Cre reacted with picric acid (PA) in the first reaction zone and then successively flowed into the detection zone, which was designed to collect the soluble orange Cre-PA complex as the reagent-sample mixed along the pathway, yielding a homogeneous color distribution. The lamination of the PADs prevents solution evaporation and weakens capillary flow, allowing precise sampling volumes without the use of a micropipette. The PADs provide a linear relationship between Cre concentrations and green intensity within a range of 10.0-50.0 mg/dL with correlation coefficient of r(2) > 0.99. The limit of detection and quantification are 2.8 and 9.5 mg/dL, respectively. The intraday (n = 2) and interday (n = 4) precision, reported as a relative standard deviation (%RSD), were 5.1 %, and 5.7 %, respectively. The developed devices show good tolerance under the accelerated storage conditions at 4 degrees C and 25 degrees C for 2 years. The developed PADs were employed to analyze Cre in 10 clinical urine samples obtained from Srinagarind Hospital. The measured Cre concentrations ranged from 141.8 to 285.3 mg/dL, with accuracy of 82.8-114.2 %. The results showed good agreement with the enzymatic colorimetric assay, confirming the high accuracy of the developed PADs.

Background Meningiomas (MGs) are the most common primary brain tumors, arising from arachnoid cap cells within the meninges. There is currently no validated, clinically used serum marker for brain tumors; diagnosis still relies on imaging and histopathology/molecular testing of resected tissue. Several serum biomarker candidates are under active investigation. In this study, we explored the potential of serum mucin-4 (MUC4) and mucin-1 (MUC1) glycoproteins as tumor markers for detecting MG and other benign/malignant brain tumors (BTs). Methods We used an in-house lectin-based ELISA to measure serum MUC4 and MUC1 in patients with MG, benign BTs, and glioblastoma (GBM), compared with healthy controls (HE). We assessed the diagnostic and prognostic power of serum MUC4 and MUC1. Results In MG, BTs, and GBM, the MUC4/MUC1 ratio was substantially higher than in HE. ROC analysis suggested that the serum MUC4/MUC1 ratio can significantly classify MG, GBM, or BTs from HE. A higher MUC4/MUC1 ratio was linked to the malignant nature of brain tumors, as GBM showed a higher MUC4/MUC1 ratio than MG. Conclusions We have demonstrated a possible role for mucin glycoproteins and their glycosylation in the development and progression of brain tumors.

Chronic kidney disease (CKD) is increasingly linked to environmental toxins, including the cyanobacterial toxin microcystin-LR (MC-LR), particularly in populations with pre-existing renal injury. We have previously demonstrated that MC-LR promotes CKD, however the full underlying mechanism remains poorly understood. This study investigated how MC-LR exacerbates adenine-induced kidney disease in animal models using an integrative multi-omics approach. Male Sprague-Dawley rats were assigned to four groups: control, MC-LR, adenine, and adenine + MC-LR. Histopathology showed that MC-LR alone caused only mild, focal interstitial inflammation and fibrosis, whereas adenine alone induced granulomatous interstitial nephritis with tubular atrophy and acute tubular necrosis. The most severe lesions were in the co-exposure group, with widespread tubular injury, dense granulomatous inflammation, and extensive interstitial fibrosis. Proteomic analysis revealed distinct clustering and overexpression of Ctss, Wipf3, and Hmgcs2 in kidney tissue from the co-exposure group, together with enrichment of pathways related to DNA repair, p53 signaling, and integrin-HMGB1 complexes. Urinary metabolomics and peptidomics revealed metabolic and peptide signatures associated with CAMKK2 signaling, Farnesyl CoQ10, ferroptosis, and immune activation. Integrative multi-omics analysis demonstrated strong cross-omics correlations, highlighting coordinated oxidative stress, mitochondrial dysfunction, ferroptosis, altered mitophagy, and fibrotic remodeling as key mechanisms of MC-LR-enhanced nephrotoxicity. Together, these findings show that even sub-toxic, environmentally relevant MC-LR exposure can amplify kidney injury through tightly interconnected metabolic and inflammatory networks. This work provides mechanistic insight into cyanotoxin-associated kidney disease and supports the need for stricter monitoring and prevention strategies in regions affected by harmful algal blooms.

Artocarpus lakoocha agglutinin (ALA), which specifically targets the Gal/GalNAc components of complex glycans, was isolated from the seeds of Artocarpus lakoocha. This study is the first to explore the role of ALA in identifying aberrant glycans, designated ALA-binding glycans (ALAG), and its implications in cholangiocarcinoma (CCA). ALA-histochemistry was used to evaluate ALAG expression in liver fluke-induced CCA tissues from hamsters (n = 60). Elevated ALAG expression was observed in hyperplastic ducts and significantly increased in CCA tissues, while normal biliary epithelium and hepatocytes showed no expression. Similar results were found in patient CCA tissues (n = 68), where higher ALAG levels correlated with shorter survival rates, indicating the involvement of ALAG in CCA development and progression. Furthermore, ALA treatment inhibited cell viability in CCA cell lines, as demonstrated by MTT and colony formation assays, and Ki-67 expression. ALA treatment also decreased cell migration and invasion, as shown by Transwell assays. Gelatin zymography suggested that these effects might be associated with reduced MMP-9 activity. Overall, these findings may position ALAG as a potential marker for poor prognosis in CCA, while ALA may serve as a novel lectin for both detection and therapeutic applications in CCA.

Monosodium glutamate (MSG) is widely used as a food additive and flavor enhancer, but concerns have emerged regarding its potential effects on kidney function and vitamin B6 metabolism. This study investigated the impact of varying levels of dietary MSG intake on vitamin B6 status in a rat model. Male Wistar rats were divided into four groups and administered MSG in their drinking water at concentrations of 0, 0.5, 1.5, and 3.0 g % for 12 weeks. Three isoforms of vitamin B6, pyridoxal (PL), pyridoxal 5'-phosphate (PLP), and pyridoxic acid (PA), were measured in plasma, liver, kidney, and urine using HPLC-MS. Kidney metabolites were analyzed by 1H nuclear magnetic resonance spectroscopy to assess MSG-related metabolic changes. We found that plasma PL and PLP levels were elevated in all MSG-treated groups compared with controls, regardless of dose. This correlated with increased hepatic PLP levels and a decreased PLP catabolic ratio (PAr). In contrast to the liver, PLP levels in the kidney were significantly lower compared to controls. Metabolomics profiling of kidney tissue revealed elevated levels of various amino acids and metabolic intermediates in the MSG-treated rats. In conclusion, MSG consumption cannot induce vitamin B6 deficiency systematically, such as in the liver and plasma, as long as dietary vitamin B6 is adequate. However, depletion of PLP occurred locally in the kidney. Because MSG consumption may affect renal vitamin B6 status, there is a need for further studies to elucidate the underlying mechanisms and assess the potential health implications of habitual MSG intake.

Chronic kidney disease of unknown etiology (CKDu) has been reported mainly in agricultural communities, in hot and humid climates, but whether this is occurring in Thailand has not been fully documented. The prevalence of CKD is higher in Northeast Thailand compared to other parts of the country and this region is hot, tropical, and agriculturally based. Therefore, we evaluated the prevalence of CKDu determined by various criteria and the associated risk factors of CKDu in this region. A population-based survey was conducted in rural sub-districts between 2017–2019 in which blood and urine samples were collected for determination of CKD, and ultrasonography was performed to evaluate for renal structural abnormalities. Public and household water were analyzed for contaminants: sixteen samples of water within the study area, encompassing natural untreated surface water sources, shallow groundwater, and locally produced tap water were collected for physical and chemical analyses based on the guidelines for drinking-water quality, as recommended by the World Health Organization (WHO) in 2011. The mandatory criteria were: suspected CKDu one time measurement CKDu1: eGFR < 60 mL/min, CKDu2: eGFR < 60 mL/min and dipstick protein ≤ 1 +, in the absence of evidence of other kidney diseases or diabetes. Further assessment included: Repeat assessment after 12 weeks, confirmed one or more of; − eGFR < 60 ml/min/1.73 m2, Albuminuria ≥ 30 mg/g Cr, Hematuria > 3 RBCs/high power field. Ultrasound criteria were confirmed parenchymatous change without other structural abnormalities, assessed by two radiologists. The prevalence of CKD was 26.85

Background: Oxidative stress arises from an imbalance between excessive oxidant production and impaired antioxidant defense systems. This imbalance leads to biomolecular damage, contributing to aging and age-related diseases such as chronic kidney disease (CKD). Oxidative stress is a well-established risk factor for CKD and has been reported to accelerate disease progression. Hesperidin, a flavanone glycoside abundant in citrus fruits, exhibits antioxidant, anti-hypertensive, and anti-inflammatory properties and has been suggested to attenuate CKD progression. However, its potential role in reversing oxidative damage in kidney cells remains unclear. Methods: This study aimed to investigate whether hesperidin can reverse oxidative damage in human kidney proximal tubular epithelial (HK-2) cells. Oxidative stress was induced by exposing HK-2 cells to 500 μM hydrogen peroxide (H2O2) for 6 h, followed by treatment with 100 μM hesperidin for 24 h. Results: Our results showed that hesperidin significantly ameliorated H2O2-induced cytotoxicity. In the hesperidin post-treatment group (H2O2 + hesperidin), the expression of the antioxidant gene manganese superoxide dismutase (MnSOD) and the longevity-associated gene sirtuin 1 (SIRT1) was upregulated, while the expression of the senescence-associated gene β-galactosidase was downregulated compared to the H2O2-only treatment. Conclusions: These findings suggest that hesperidin promotes recovery from oxidative injury in kidney cells by enhancing antioxidant and longevity pathways and reducing cellular senescence. This may contribute to improved renal health and potentially slow CKD progression in patients suffering from oxidative stress-related kidney damage.

Background The cytochrome P450 family 3 subfamily A polypeptide 5 (CYP3A5) gene plays an important role in renal function through its product’s involvement in metabolizing endogenous substances and drugs, including immunosuppressants used following kidney transplantation. A single-nucleotide polymorphism, CYP3A5*3 (rs776746), produces a non-functional variant that may influence progression of chronic kidney disease (CKD) by impairing renal filtration. However, the frequency of the CYP3A5*3 allele in the Thai population and its association with renal parameters remain underexplored. This study aimed to determine the prevalence of CYP3A5 polymorphisms and their association with renal function. Methods We investigated the distribution of CYP3A5 polymorphisms in 329 northeastern Thai participants, including 205 CKD patients and 124 healthy controls. Genotyping was performed using the TaqMan allelic discrimination assay. Renal function parameters were assessed and compared between CYP3A5*1 and CYP3A5*3 allele carriers. Results In the entire cohort, the allele frequency of CYP3A5*3 was 63.2%, with genotype frequencies of CYP3A5*1/*1 (16.7%), CYP3A5*1/*3 (40.1%), and CYP3A5*3/*3 (43.2%). There was no significant difference in the CYP3A5 allele frequencies between CKD and control groups. CYP3A5*3 carriers exhibited significantly lower eGFR, urine creatinine and serum creatinine clearance and higher UACR compared to CYP3A5*1 carriers. After adjusting for confounders, CYP3A5*3 remained significantly associated with reduced urine creatinine. Conclusion This study highlights a high prevalence of CYP3A5 polymorphisms in the northeastern Thai population. The association of the CYP3A5*3 allele with renal function parameters underscores the need for further research into the mechanisms by which CYP3A5 affects kidney function, which could inform personalized CKD management strategies.

Introduction:Kidney injury molecule-1 (KIM-1), encoded by the Hepatitis A Virus Cellular Receptor 1 (HAVCR1) gene, plays a crucial role in kidney injury progression. Although serum and urinary KIM-1 levels are established biomarkers for kidney damage, the relationship between KIM-1 levels, HAVCR1 gene polymorphism, and chronic kidney disease (CKD) stages remains unclear. This study aimed to investigate KIM-1 as a potential biomarker for CKD progression in the Thai population and explore its association with genetic polymorphisms in the HAVCR1 gene. Methods:A total of 250 patients with CKD were recruited from Khon Kaen, Thailand. Serum and urinary KIM-1 levels were measured using an indirect enzyme-linked immunosorbent assay. Single-nucleotide polymorphism (SNP) genotyping was conducted using the TaqMan assay to assess the associations between KIM-1 levels, SNPs, and CKD progression. Statistical analyses were conducted to assess the correlations between estimated glomerular filtration rate (eGFR), KIM-1 levels, and SNPs. Results:Serum and urinary KIM-1 levels showed a significant negative correlation with eGFR, indicating higher KIM-1 levels in patients with more advanced CKD. However, the rs6555820 SNP in the HAVCR1 gene did not show a significant association with KIM-1 levels or eGFR. Interestingly, a significant association between rs6555820 and gender was observed, implying a potential gender-dependent genetic impact. Conclusion:Serum and urinary KIM-1 levels have been found to be associated with CKD stages and eGFR, suggesting their potential as biomarkers for assessing CKD severity. However, no direct associations were observed between the SNP rs6555820 and KIM-1 levels or eGFR. Further research is required to elucidate the genetic mechanisms underlying CKD progression.

Meningiomas are the most common primary intracranial tumors, and improved diagnostic and therapeutic strategies are needed. Meningioma (MG) exhibits abnormal glycosylation, which can be used for diagnosis, prognosis, and treatment strategies. In this study, we use Ulex europaeus agglutinin-I (UEA-I) to develop an in-house enzyme-linked lectin assay for detecting meningioma (MG)-associated glycan in patient serum. The level of serum UEA-I binding glycan (UEAG) was significantly higher in MG and other brain tumors compared with healthy controls (HC). Moreover, we found that patients with a higher grade of MG (WHO Grade II) have a higher level of serum UEAG compared to those with Grade I. The functional analysis in MG cell lines showed that UEA-I can inhibit the migration and invasion of MG cells, with no effect on cell viability, suggesting the role of UEAG in MG progression. In conclusion, we have demonstrated the potential of UEAG as a serum glycobiomarker for diagnosis, and it may also serve as a target for MG treatment.

We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3β/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.

Background: Iron overload can lead to organ and cell injuries. Although the mechanisms of iron-induced cell damage have been extensively studied using various cells, little is known about these processes in kidney cells.Methods: In this study, we first examined the correlation between serum iron levels and kidney function. Subsequently, we investigated the molecular impact of excess iron on kidney cell lines, HEK293T and HK-2. The presence of the upregulated protein was further validated in urine.Results: The results revealed that excess iron caused significant cell death accompanied by morphological changes. Transcriptomic analysis revealed an up-regulation of the ferroptosis pathway during iron treatment. This was confirmed by up-regulation of ferroptosis markers, ferritin light chain (FTL), and prostaglandin-endoperoxide synthase 2 (PTGS2), and down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) using real-time PCR and Western blotting. In addition, excess iron treatment enhanced protein and lipid oxidation. Supportively, an inverse correlation between urinary FTL protein level and kidney function was observed.Conclusion: These findings suggest that excess iron disrupts cellular homeostasis and affects key proteins involved in kidney cell death. Our study demonstrated that high iron levels caused kidney cell damage. Additionally, urinary FTL might be a useful biomarker to detect kidney damage caused by iron toxicity. Our study also provided insights into the molecular mechanisms of iron-induced kidney injury, discussing several potential targets for future interventions.

Thailand's aging society, particularly in rural areas, faces healthcare challenges as younger populations move to cities. Elderly residents often suffer from diabetes and hypertension, making hospital visits difficult. We propose a novel aptasensor for detecting urinary albumin, using DNA aptamer and graphene oxide, with detection limits of 50 ng/mL. Field trials showed 12% of 84 samples had elevated albumin levels, and 50% indicated early kidney dysfunction. This portable, point-of-care sensor can enhance early kidney disease detection and management in rural elderly populations, improving health outcomes.

Introduction: Chronic kidney disease (CKD) is a major health problem in Thailand and health behaviors are central to its risk and progression. Because of the shortage of healthcare personnel, village health volunteers (VHVs) have been collaborating in the primary health care system. However, the contribution of VHVs to CKD reduction has not been evaluated yet. This study aimed to evaluate the efficacy of the VHV-integrated model in preventing and slowing down CKD and its risk factors. Methods: The population-based cohort study was conducted in a rural community of Thailand between 2017 and 2019. Baseline clinical and behavioral characteristics including CKD, diabetes, hypertension, and other high-risk factors of the participants were collected. The integrated care model was initiated by the multidisciplinary care team that facilitated, empowered, and trained VHVs targeting risk factors of CKD, health literacy, and health promotion. Then the participants were educated and trained for lifestyle modification and were monitored continuously for 18 months by VHVs. Changes in the CKD risk factors, and kidney functions before and after the application of integrated care model were compared. Results: A total of 831 subjects participated in the study with an average age of 57.5 years, and 69.5% were female. Among them, 222 participants (26.7%) were diagnosed as having CKD, the vast majority (95%) of which were in the early stages (G1-G3 and A1-A2). CKD risk factors such as high salt intake, smoking, alcohol consumption, self-NSAID (non-steroidal anti-inflammatory drugs) use were significantly decreased after application of the care model. Also, hemoglobin A1c was significantly reduced in diabetic patients, and blood pressure was controlled better than before in the hypertensive patients. Most importantly, a decline of estimated glomerular filtration rate of the CKD group was improved and lower than the non-CKD group. Conclusion: The integrated care model through VHV significantly attenuated the risk factors associated with CKD in the general and high-risk population and effectively slowed down the progression of CKD.