1.Evolving Molecular Subtypes of Gastric Cancer: From Past Classifications to Present Consensus and Future Directions for Precision Therapy
Journal of Gastric Cancer 2026;26(1):16-30
Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multiomic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes.Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy.Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal growth factor receptor 2 amplification, microsatellite instability, and programmed death-ligand 1 expression are now used clinically to guide treatment with targeted agents and immune checkpoint inhibitors. Emerging single-cell and spatial transcriptomic analyses have further refined this landscape by deconstructing tumor microenvironments and potential evolutionary trajectories associated with disease progression. This review examines the evolution of molecular classification systems for gastric cancer, highlights current consensus frameworks, and discusses how subtype-based stratification will transform clinical trial design and enable biomarker-driven precision therapy.
2.Recent Advances in Therapeutic Approaches for Knee Osteoarthritis: a Narrative Review
Md. Solayman HOSSAIN ; Hyun Jae LEE ; Rajib HOSSAIN ; Chang Moo KIM ; Choong Jae LEE ; Sun-Chul HWANG
Biomolecules & Therapeutics 2026;34(1):80-101
Knee osteoarthritis (KOA) is a progressive and chronic musculoskeletal condition that continues to be the leading cause of disability worldwide. Conventional treatment approaches for the management of KOA largely focus on symptom alleviation rather than halting or reversing disease progression. However, recent advancements have highlighted the integrated interplay of mechanical stress, inflammation, cellular senescence, and chondrocyte dysfunction in the progression of KOA, in turn prompting new therapeutic strategies. Therefore, emerging interventions such as regenerative medicine, gene therapy, senolytic, platelet-rich plasma (PRP), disease-modifying osteoarthritis drugs (DMODs), and biologics have broadened the therapeutic options. Additionally, natural compounds demonstrated potential in KOA treatment with promising chondroprotective and anti-inflammatory effects.Moreover, digital technologies and clinical and molecular phenotyping enhanced early diagnosis, monitoring, and personalized management of the disease. Therefore, the current narrative review focuses on the molecular insights, clinical outcomes and prospects for the rapidly evolving landscape of current and emerging treatment approaches for the management of knee osteoarthritis (KOA).
3.Ferroptosis-Driven Senescence Loop as a Central Amplifier of Osteoarthritis Progression
Rajib HOSSAIN ; Hyun Jae LEE ; Md. Solayman HOSSAIN ; Jiwon JEONG ; Choong Jae LEE ; Sun-Chul HWANG
Biomolecules & Therapeutics 2026;34(3):506-518
Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.
4.Risk Assessment for Ramadan Fasting in People With Diabetes in Hospital-Based Diabetes Clinics Using the Updated 2026 IDF-DAR Risk Calculator
Raja Nurazni Raja Azwan ; Chin Voon Tong ; Lisa Mohamed Nor ; Marisa Khatijah Borhan ; Syarifah Syahirah Syed Abas ; Poh Shean Wong ; Ying Jie Tan ; Shartiyah Ismail ; Eunice Yi Chwen Lau ; Yueh Chien Kuan ; Noor Hafis Md Tob ; Shu Teng Chai ; Pei Lin Chan ; Xe Hui Lee ; Wei Wei Ng ; Jin Hui Ho ; Miza Hiryanti Zakaria ; Rabeah Md Zuki ; Wan Mohd Hafez Wan Hamzah ; Melissa Vergis ; Choon Peng Sun ; Vanusha Devaraja Pillai ; Chee Koon Low ; Shazatul Reza Mohd Redzuan ; Xin-Yi Ooi ; Siti Sanaa Wan Azman ; Deviga Lachumanan ; Saiful Shahrizal Shudim ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):42-43
Introduction:
The 2021 IDF-DAR risk calculator had been previously
evaluated in multiple studies and subsequently widely
accepted and applied in clinical practice as a practical
standardized tool for patient risk stratification. Recently
updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating
modern diabetes technologies, including continuous
glucose monitoring (CGM), automated insulin delivery
(AID) systems, and advanced insulin formulations to
enhance risk stratification. This tool allows medical
professionals to tailor Ramadan practices based on overall
factors toward promoting safe fasting.
Methodology:
This prospective multicentre observational study recruited
adults with Type 1 and Type 2 diabetes attending public
hospitals nationwide. People with diabetes (PwD) intending
to perform Ramadan fasting were invited to participate
and assessed using the 2026 IDF-DAR Risk Calculator in
the 6-week pre-Ramadan period between 30th January and
19th March 2026.
Results:
A total of 458 PwD were evaluated and stratified into low
(15.7%), moderate (41%), and high risk (43.3%) categories.
Most participants had Type 2 diabetes (83.6%), with 60.3%
having a disease duration exceeding 10 years and 43%
exhibiting poor glycemic control (hemoglobin A1c >9%).
Insulin therapy was used by 76.4% of participants, including
two individuals with Type 1 diabetes using AID systems.
Most participants reported no recent hypoglycemia (76.4%),
81.0% performed glucose monitoring, and 3.3% used CGM.
Severe comorbidities were uncommon, with 1.1% having
unstable macrovascular disease and 4.4% advanced chronic
kidney disease (estimated glomerular filtration rate <30).
Notably, 72.2% received structured Ramadan education.
Conclusion
Majority of PwD attending tertiary diabetes clinics were
in the moderate- to high-risk category and intended to
fast despite medical advice against fasting in some cases.
Although most participants were on insulin therapy,
hypoglycemia was low in the pre-Ramadan period.
Integration of modern technologies, advanced insulin
therapies, and structured education may support safer
fasting practices.
Risk Assessment
;
Diabetes Mellitus
;
Hospitals
;
Fasting
5.Prevalence and Neonatal Predictors of Metabolic Bone Disease of Prematurity in Hospital Tunku Azizah Kuala Lumpur
Muhamad Hanif Halim ; Choi Siang Choong ; Arini Nuran Md Idris ; Yee Lin Lee
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):127-
Introduction:
Metabolic bone disease of prematurity (MBDP) is characterized by biochemical and radiological findings related to bone
demineralization in premature babies. Despite early recognition, MBDP is still a prevalent problem and is associated with
significant morbidities in premature babies. This study aims to determine the prevalence and neonatal predictors of MBDP.
Methodology:
This retrospective cross-sectional study involved premature babies with gestational age ≤32 weeks and birth weight ≤1.5
kg, admitted to Hospital Tunku Azizah, Kuala Lumpur, between January 1, 2020, and January 31, 2024. Babies whose
serum phosphate was ≤1.5 mmol/L and serum alkaline phosphatase >500 IU/L at 3–6 weeks of age fulfilled the diagnosis
of MBDP. The maternal and neonatal characteristics of the study population were retrieved from the medical records.
Neonatal predictors for MBDP were analyzed by simple and multiple logistic regression.
Results:
A total of 292 subjects were enrolled. The prevalence of MBDP was 13.4%. On simple logistic regression, male gender, low
gestational age, poor APGAR score, delayed enteral feed initiation, prolonged TPN, delayed vitamin D supplementation,
use of unfortified expressed breast milk, patent ductus arteriosus, and bronchopulmonary dysplasia, cholestasis, prolonged
hospital stay, and prolonged ventilation were risk factors for MBDP (p <0.05). On multiple logistic regression, only cholestasis
(p 0.014), prolonged TPN use (p <0.001), and prolonged hospitalization (p <0.001) were independent neonatal predictors
for MBDP.
Conclusion
The risk of MBDP can be reduced by shortening TPN duration and hospitalization duration and preventing cholestasis.
This may be achieved by early enteral feeding initiation and use of fortified EBM, thus preventing the development of
MBDP.
Infant, Newborn
;
Prevalence
;
Bone Diseases, Metabolic
;
Hospitals
6.Hederacoside C Modulates EGF-Induced MUC5AC Mucin Gene Expression by Regulating the MAPK Signaling Pathway in Human Airway Epithelial Cells
Rajib HOSSAIN ; Md. Solayman HOSSAIN ; Hyun Jae LEE ; Choong Jae LEE
Biomolecules & Therapeutics 2025;33(3):510-517
This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.
7.Stem Cell-Based Approaches in Parkinson’s Disease Research
Min Seong KIM ; Subeen YOON ; Jiwoo CHOI ; Yong Jun KIM ; Gabsang LEE
International Journal of Stem Cells 2025;18(1):21-36
Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don’t alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.
8.Risk Factors for “Adjacent-Level Ossification Development” Other Than Short Plate-to-Disc Distance and Clinical Implications for Adjacent-Segment Pathology
Sang Hun LEE ; Micheal RAAD ; David B. COHEN ; Khaled M. KEBAISH ; Lee H. RILEY III
Neurospine 2025;22(1):194-201
Purpose:
To identify factors associated with adjacent-level ossification development (ALOD) after anterior cervical discectomy and fusion (ACDF) and associated clinical outcomes.
Methods:
We retrospectively reviewed records of 140 adults who underwent primary ACDF for degenerative disc disease. We compared patients with and without ALOD after ACDF. Radiographic measurements and factors associated with ALOD were assessed preoperatively and at minimum 24-month follow-up. Clinical outcomes were incidence of clinical adjacent-segment pathologies (CASP), revision surgery, and patient-reported outcomes.
Results:
Factors associated with both cranial and caudal ALOD were short plate-to-disc distance (PDD), adjacent-segment kyphosis, hyperlordotic ACDF causing junctional segment kyphosis, and preoperative ossification of the anterior longitudinal ligament (OALL). Mean final adjacent-segment range of motion (ROM) was less in those with cranial ALOD (6.9° ± 2.8°) than in those without cranial ALOD (12° ± 4.2°) (p < 0.01). Mean final adjacent-segment ROM was also less in those with caudal ALOD (5.5° ± 2.4º) than in those without caudal ALOD (8.2º ± 3.7º) (p < 0.01). The incidence of CASP-required surgery was higher in those with caudal ALOD (p = 0.02) but no different in those with cranial ALOD (p = 0.69) compared with those without ALOD.
Conclusion
Factors associated with ALOD were a kyphotic segment adjacent to ACDF, hyperlordotic fusion, preoperative OALL, and short PDD. ALOD was associated with less segmental ROM and, for those with caudal but not cranial ALOD, higher incidence of revision surgery for CASP.
9.Prevalence of asymptomatic malaria in high- and low-transmission areas of Tanzania: The role of asymptomatic carriers in malaria persistence and the need for targeted surveillance and control efforts
Ernest MAZIGO ; Hojong JUN ; Wang-Jong LEE ; Johnsy Mary LOUIS ; Fadhila FITRIANA ; Jadidan Hada SYAHADA ; Fauzi MUH ; Feng LU ; Md Atique AHMED ; Seok Ho CHA ; Wanjoo CHUN ; Won Sun PARK ; Se Jin LEE ; Sunghun NA ; Joon-Hee HAN ; Nyalali KIJA ; Smart GEODFREY ; Eun-Teak HAN ; Jim TODD ; Alphaxard MANJURANO ; Winifrida KIDIMA ; Jin-Hee HAN
Parasites, Hosts and Diseases 2025;63(1):57-65
As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.
10.Risk Factors for “Adjacent-Level Ossification Development” Other Than Short Plate-to-Disc Distance and Clinical Implications for Adjacent-Segment Pathology
Sang Hun LEE ; Micheal RAAD ; David B. COHEN ; Khaled M. KEBAISH ; Lee H. RILEY III
Neurospine 2025;22(1):194-201
Purpose:
To identify factors associated with adjacent-level ossification development (ALOD) after anterior cervical discectomy and fusion (ACDF) and associated clinical outcomes.
Methods:
We retrospectively reviewed records of 140 adults who underwent primary ACDF for degenerative disc disease. We compared patients with and without ALOD after ACDF. Radiographic measurements and factors associated with ALOD were assessed preoperatively and at minimum 24-month follow-up. Clinical outcomes were incidence of clinical adjacent-segment pathologies (CASP), revision surgery, and patient-reported outcomes.
Results:
Factors associated with both cranial and caudal ALOD were short plate-to-disc distance (PDD), adjacent-segment kyphosis, hyperlordotic ACDF causing junctional segment kyphosis, and preoperative ossification of the anterior longitudinal ligament (OALL). Mean final adjacent-segment range of motion (ROM) was less in those with cranial ALOD (6.9° ± 2.8°) than in those without cranial ALOD (12° ± 4.2°) (p < 0.01). Mean final adjacent-segment ROM was also less in those with caudal ALOD (5.5° ± 2.4º) than in those without caudal ALOD (8.2º ± 3.7º) (p < 0.01). The incidence of CASP-required surgery was higher in those with caudal ALOD (p = 0.02) but no different in those with cranial ALOD (p = 0.69) compared with those without ALOD.
Conclusion
Factors associated with ALOD were a kyphotic segment adjacent to ACDF, hyperlordotic fusion, preoperative OALL, and short PDD. ALOD was associated with less segmental ROM and, for those with caudal but not cranial ALOD, higher incidence of revision surgery for CASP.


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