1.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
2.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
3.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
4.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
5.Cross-reactive IgE-binding proteins from Philippine allergenic weeds and trees pollen extracts.
Maria Katrina Diana M. CRUZ ; Mary Anne R. CASTOR ; Krystal M. HATE ; Gregg Austine M. BALANAG ; Roche Dana C. REYES ; Maria Socorro AGCAOILI-DE JESUS ; Cherie C. OCAMPO-CERVANTES ; Leslie Michelle M. DALMACIO
Acta Medica Philippina 2025;59(Early Access 2025):1-6
BACKGROUND
The Philippines has a wide variety of plant species with potential to produce allergenic pollen grains. Most of the study subjects which are residents in Manila tested positive to Fabaceae and Amaranthaceae. Weeds, especially the Amaranthaceae and Fabaceae families, are relevant triggers of allergy as they are highly adaptive and can grow despite adverse weather conditions. However, only a few allergens have been identified among these families and listed in the International Union of Immunological Societies allergen nomenclature database. Currently, local pollen grains are being processed at the Medical Research Laboratory of our institution to produce crude pollen extracts for use in specific diagnostic skin tests and in subcutaneous immunotherapy of patients with respiratory allergies all over the country. However, these extracts have not been characterized and data of cross-reactivity is limited.
OBJECTIVESThis study aimed to evaluate the IgE binding activity of allergen extracts from Philippine weeds and trees, and determine their cross-reactive components.
METHODSPollen extracts from Amaranthus spinosus (pigweed), Mimosa pudica (makahiya), Tridax procumbens (wild daisy), Albizia saman (acacia), Leucaena leucocephala (ipil-ipil), Mangifera indica (mango), and Cocos nucifera (coconut) were extracted and analyzed for crossreactivity using ELISA and Western blot.
RESULTSCross-reaction was observed between ipil-ipil and coconut, and between makahiya and wild daisy. IgE bound to protein components at ~20, 18, and 15 kDa of the weeds, while for the trees, IgE bound to protein components at ~35 and ~15 kDa which may be responsible for the cross-inhibitions observed.
CONCLUSIONData may contribute to the development of immunotherapeutic strategies and diagnostic applications for respiratory allergies, comprising the production of standardized panel of allergens thus eliminating unwanted side effects and providing patients with safer diagnosis and therapy.
Plants ; Pollen ; Allergens ; Amaranthus ; Arecaceae
6.Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model
Diana M. ELIZONDO ; Lais L. de Oliveira REKOWSKY ; Ayane de Sa RESENDE ; Jonathan SEENARINE ; Ricardo Luis Louzada da SILVA ; Jamel ALI ; Dazhi YANG ; Tatiana de MOURA ; Michael W. LIPSCOMB
Tissue Engineering and Regenerative Medicine 2025;22(1):43-55
Background:
Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required.
Methods:
Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments.
Results:
Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial.
Conclusion
These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.
7.The development of an order set for adults admitted for acute heart failure at a National University Hospital in the Philippines.
John Vincent U. MAGALONG ; Felix Eduardo R. PUNZALAN ; Marie Kirk Patrich A. MARAMARA ; Frederick Berro B. RIVERA ; Zane Oliver O. NELSON ; Bai Sitti Ameerah B. TAGO ; Cecileen Anne M. TUAZON ; Ruth Divine D. AGUSTIN ; Lauren Kay M. EVANGELISTA ; Michelle Marie Q. PIPO ; Eugenio B. REYES ; John C. ANONUEVO ; Diana R. TAMONDONG-LACHIC
Acta Medica Philippina 2025;59(3):45-56
BACKGROUND AND OBJECTIVES
Heart Failure (HF) remains a major health concern worldwide. In the Philippine General Hospital (PGH), HF is consistently a top cause of mortality and readmissions among adults. The American College of Cardiology (ACC) and European Society of Cardiology (ESC) published guidelines for interventions that improve quality of life and survival, but they are underused and untested for local acceptability. Hospitals overseas used order sets created from these guidelines, which resulted in a considerable decrease in in-hospital mortality and healthcare costs. We aimed to develop an order set for adult patients with acute heart failure (AHF) admitted to the PGH Emergency Department (ED) to improve care outcomes.
METHODSThis study utilized a mixed methods approach to create the AHF order set. ESC and ACC HF guidelines were appraised using the AGREE II tool. Class I interventions for AHF were included in the initial order set. Through focused group discussions (FGD), clinicians and other care team members involved in the management of AHF patients at PGH ED modified and validated the order set. Stakeholders were asked to use online Delphi and FGD to get a consensus on how to amend, approve, and carry out the order given.
RESULTSUpon review of HF guidelines, 29 recommendations on patient monitoring, initial diagnostic, and therapeutic interventions were adopted in the order set. Orders on subspecialty referrals and ED disposition were introduced. The AHF patient was operationally defined in the setting of PGH ED. The clinical orders fit the PGH context, ensuring evidence-based, cost-effective, and accessible care responsiveness to patients’ needs and suitable for local practice. Workflow changes due to COVID-19 were considered. Potential barriers to implementation were identified and addressed. The final order set was adopted for implementation through stakeholder consensus.
CONCLUSIONThe PGH developed and adopted its own AHF order set that is locally applicable and can potentially optimize outcomes of care.
Human ; Quality Of Life ; Critical Pathways ; Quality Improvement
8.Health protocol practices and personal preventive measures among fully vaccinated individuals with comorbidities in the National Capital Region, Philippines during the COVID-19 pandemic: A mixed-method study.
Maria Luisa OLANO ; Matthew Spencer T. HO ; Mareeya P. YUMENA ; Diana Leah MENDOZA ; Patricia Anne C. TY ; Erin Grace B. VILLANUEVA ; Christine Rozien M. PALAYAD ; Jaye Kirsten U. MELCHOR ; Chrissea B. CUSTODIO
Acta Medica Philippina 2025;59(4):26-41
BACKGROUND AND OBJECTIVE
The Philippine Inter-Agency Task Force for the Management of Emerging Infectious Diseases implemented health protocol guidelines to reduce the risk of COVID-19 transmission. Individuals with comorbidities were advised to take precautionary measures due to their increased vulnerability. This study aimed to assess the relationship between knowledge, acceptance, and adherence to health protocols among fully vaccinated individuals with comorbidities in the National Capital Region, Philippines.
METHODSThe study employed an explanatory-sequential mixed-method design. The quantitative phase involved an online survey with 384 respondents. The survey included questions on socio-demographic profile, COVID-19 knowledge, acceptability of health protocols, and adherence to preventive practices. Chi-square Test of Independence and Pearson’s Correlation Test were used to analyze the data. Semi-structured interviews were conducted with 11 participants, providing rich insights into their personal experiences. The interview transcripts were analyzed using Colaizzi’s descriptive method with the aid of qualitative analysis software (MAXQDA), ensuring a rigorous approach to thematic analysis. The integration of the two phases was achieved by connecting quantitative results with qualitative insights, creating a comprehensive understanding of the phenomena under study.
RESULTSFindings showed that the relationship of sociodemographic characteristics and level of knowledge (Gender pCONCLUSION
The study suggests that multiple factors contribute to non-adherence to health protocols. Recognizing these holes and weaknesses in the COVID-19 pandemic response stresses the need for national leaders to place urgency on properly implementing preventive measures and providing health education to the masses during public health situations. Collaboration from all sectors is crucial in addressing public health crises. This study can be a valuable resource for future researchers, local government units, and policymakers in prioritizing public health care and pandemic preparedness.
Human ; Comorbidity ; Covid-19 ; Public Health Practice ; Vaccines
9.Accuracy of the Brighton Pediatric Early Warning Score in detecting clinical deterioration events among pediatric patients: Retrospective cohort study
Giselle Godin ; Mae Anne Cansino-Valeroso ; Diana M. Dadia
Southern Philippines Medical Center Journal of Health Care Services 2025;11(1):8-8
BACKGROUND
Pediatric Early Warning Scores (PEWS) help identify children at risk of clinical deterioration, but their accuracy across diverse settings, populations, interventions, and outcomes remains unexplored.
OBJECTIVETo determine the accuracy of PEWS in detecting clinical deterioration events (CDE) among pediatric patients seen at the emergency department (ED).
DESIGNRetrospective cohort study.
PARTICIPANTSPediatric patients aged 1 month to 18 years seen at the ED.
SETTINGSouthern Philippines Medical Center Emergency Department, Davao City, Philippines from January 2021 to December 2022.
MAIN OUTCOME MEASURESArea under the curve (AUC) of PEWS in detecting CDE; Brighton PEWS optimal cut-off and its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR).
MAIN RESULTSAmong the 345 patients, 56 experienced CDE and 289 did not. Patients with CDE had significantly lower median age (1.00 year vs 5.00 years; p < 0.001), oxygen saturation (93.00% vs 98.00%; p < 0.001), and pediatric Glasgow Coma Scale scores (8.00 vs 15.00; p < 0.0001) compared to those without CDE. Heart rate (135.00 vs 111.00 beats per minute; p < 0.001), and respiratory rate (32.50 vs 24.00 breaths per minute; p < 0.001) were significantly higher in patients with CDE. The two groups also differed significantly in terms of comorbidity distribution (p < 0.001) and diagnosis (p < 0.001). The AUC of Brighton PEWS was 0.9064 (95% CI 0.8716 to 0.9357), with an optimal cut-off score of ≥4.00. This threshold yielded 76.79% sensitivity, 88.58% specificity, 56.60% PPV, 95.20% NPV, 6.72 LR+, and 0.26 LR-.
CONCLUSIONThe Brighton PEWS demonstrates strong diagnostic accuracy in predicting CDE among pediatric patients. A cut-off score of ≥4.00 offers a balanced combination of sensitivity, specificity, and likelihood ratios for ED application.
Human ; Emergency Departments ; Emergency Service, Hospital ; Resuscitation ; Mortality
10.Comparative copy number variation profiling of GL01, an immortalized non-small cell lung cancer cell line derived from a Filipino patient, and A549 lung adenocarcinoma cells.
Treena Rica D. TEH ; Kim Claudette J. FERNANDEZ ; Maria Katrina Diana M. CRUZ ; Patrick Gabriel G. MORENO ; Ruel C. NACARIO ; Gladys C. COMPLETO ; Francisco M. HERALDE III
Acta Medica Philippina 2025;59(10):37-51
BACKGROUND AND OBJECTIVES
Cell lines serve as invaluable tools in studying lung cancer biology and developing new therapies to combat the disease. However, commercially available cell lines are typically of Caucasian origin and may be less representative of the local genetic background. To address this, our lab previously immortalized cells from pleural fluid of a Filipino non-small cell lung cancer (NSCLC) patient via CDK4 transduction. Copy number variations (CNVs) are a type of genetic variation which may affect physiology and disease by disrupting gene function or altering gene expression, and in cancer, these may be associated with patient outcomes. CNV profiling can be valuable for understanding the biology of our immortalized cells and identifying genes that could serve as potential targets for diagnostic, prognostic, and therapeutic interventions. This study aimed to characterize previously immortalized NSCLC-derived cells, GL01, in comparison with an established lung adenocarcinoma (LUAD) cell line, A549, through whole-genome microarray-based copy number profiling.
METHODSDNA was extracted from GL01 and A549 cells using a commercially-available silica-based DNA extraction kit. DNA extracts were quantified and normalized for microarray analysis. Whole-genome copy number profiling was done using the OncoScan CNV Plus Assay following the manufacturer’s protocols, and data was analyzed using the Chromosome Analysis Suite software. Functional analysis of genes identified to be involved in copy number aberrations was done using the PANTHER Classification System.
RESULTSCopy number aberrations span 1,592,737,105 bp in GL01 and 1,715,708,552 bp in A549, with a high degree of concordance between the two. Large-scale and focal copy number aberrations previously identified to be recurrent in various LUAD cohorts were present in both GL01 and A549. Focal copy number aberrations associated with previously described lung cancer-related genes involve the PDE4D gene in GL01 and the SKIL and CDKN2A/CDKN2B genes in both GL01 and A549. PANTHER Pathway analysis of genes positively correlated with mRNA expression showed that the ubiquitin proteasome pathway was significantly overrepresented in both GL01 (FDR p = 0.000074) and A549 (FDR p = 0.000075), with 20 genes involved. Additionally, the KRAS:p.G12C/S:c.34G>T/A somatic mutation variant was detected in both GL01 and A549.
CONCLUSIONThis study provides a method for identifying potentially clinically-relevant genes associated with a sample’s copy number aberrations and the pathways they represent, providing personalized mechanistic, prognostic, and therapeutic insights into the cancer biology of our cells.
Human ; Carcinoma, Non-small-cell Lung ; Adenocarcinoma Of Lung


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