Publications by Year: 2026

The gut microbiome is defined as the collective assembly of microbial communities inhabiting the gut, along with their genes and metabolic products. The gut microbiome systematically regulates host metabolism, immunity, and neuroendocrine homeostasis via interspecies interaction networks and inter-organ axes. Given the importance of the gut microbiome to the host, this review integrates the composition, function, and genetic basis of the gut microbiome with host genomics to provide a systematic overview of recent advances in microbiome-host interactions. This encompasses a complete technological pipeline spanning from in vitro to in vivo models to translational medicine. This technological pipeline spans from single-bacterium CRISPR editing, organoid-microbiome co-culture, and sterile/humanized animal models to multi-omics integrated algorithms, machine learning causal inference, and individualized probiotic design. It aims to transform microbiome associations into precision intervention strategies that can be targeted and predicted for clinical application through interdisciplinary research, thereby providing the cornerstone of a new generation of precision treatment strategies for cancer, metabolic, and neurodegenerative diseases.

Background/Objectives: There is limited data regarding the association of anti-drug antibody (ADA) levels with the efficacy of anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). We aimed to investigate the association between antibody to adalimumab (ATA) and antibody to infliximab (ATI) levels and treatment failure in IBD. Methods: This single-center, retrospective cohort study included consecutive IBD patients with ADA evaluated with a drug-tolerant assay between September 2012 and February 2023. A time-to-event analysis was performed for treatment failure, defined as the need for drug discontinuation due to primary non-response, loss of response, a serious adverse event, or an IBD-related surgery. Patients were followed from first positive ADA until treatment failure or the end of the follow-up (May 2024). Results: The study population consisted of 134 patients with IBD [n = 58 (43%) on adalimumab; n = 86, (64%) with Crohn's disease]. Multiple COX regression analysis identified higher ADA levels to be associated with treatment failure (HR: 1.034, 95%CI: 1.024-1.045, p < 0.001). A ROC analysis identified an ATA and ATI level threshold of 5.2 U/mL (AUC: 0.705; 95%CI: 0.569-0.841; p = 0.003; sensitivity: 64%; specificity: 82%) and 8.8 U/mL (AUC: 0.809; 95%CI: 0.713-0.906; p < 0.001; sensitivity: 69%; specificity: 93%), respectively, to distinguish patients with or without treatment failure. Conclusions: In this large retrospective cohort study, higher levels of ADA were associated with treatment failure to anti-TNF therapy in IBD. Moreover, we identified ATA and ATI level thresholds of 5.2 U/mL and 8.8 U/mL, respectively, to be associated with treatment failure.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in hematologic malignancies but has limited efficacy in solid tumors due to tumor microenvironment (TME) barriers that impede CAR T cell recognition, infiltration, and sustained function. Traditional 2D assays inadequately recapitulate these constraints, necessitating improved in vitro models. This study validated a 3D tumor spheroid platform using an agarose microwell system to generate uniform B7-H3-positive spheroids from multiple solid tumor cell lines, enabling the evaluation of CAR T cell activity. TME-relevant immune modulation under 3D conditions was analyzed by flow cytometry for B7-H3, MHC I/II, and antigen processing machinery (APM), followed by co-culture with B7-H3 CAR T cells to assess cytotoxicity, spheroid integrity, tumor viability, and CAR T cell activation, exhaustion, and cytokine production. Two human cancer-cell-line-derived spheroids, DU 145 (prostate cancer) and SUM159 (breast cancer), retained B7-H3 expression, while MC38 (mouse colon cancer)-derived spheroids served as a B7-H3 negative control. Under 3D culture conditions, DU 145 and SUM159 spheroids acquire TME-like immune evasion characteristics and specifically downregulated MHC-I and APM (TAP1, TAP2, LMP7) with concurrent upregulation of MHC-II and calreticulin. Co-culture showed effective spheroid infiltration, cytotoxicity, and structural disruption, with infiltrating CAR T cells displaying higher CD4+ fraction, activation, exhaustion, effector/terminal differentiation, and IFN-γ/TNF-α production. This 3D platform recapitulates critical TME constraints and provides a cost-effective, feasible preclinical tool to assess CAR T therapies beyond conventional 2D assays.

Traumatic brain injury (TBI) is a leading cause of critical illness and mortality in children. Transfusion of blood products, a common intervention in the management of pediatric TBI, has important implications for related principles, including trauma-induced coagulopathy, cerebral perfusion, and cerebral oxygen delivery. Knowledge gaps persist due to the limited availability of pediatric-specific data regarding blood product transfusion in TBI. In particular, there is a lack of prospective studies defining appropriate specific laboratory thresholds and transfusion targets, as well as insufficient evidence to guide the weighing of potential benefits against transfusion-related risks in this population. Although blood product transfusion in pediatric TBI has been associated with worse clinical outcomes, the underlying mechanisms and contributing factors remain poorly understood. In this review, we aimed to describe the pediatric literature on component and whole blood product transfusion in children with TBI and the pathophysiological mechanisms underlying the development of coagulopathy in this population. In addition, we incorporated available pediatric guidelines and recommendations specific to the setting of acute brain injury.

Immunogenic cell death (ICD) is a programmed pathway leading to cell death and promotion of immunological responses. Melanoma is resistant to chemotherapy and radiotherapy (RT). Disulfiram (DSF), which forms complexes with copper (Cu), has been shown to induce ICD of many tumor types. Here, we aim to investigate whether DSF/Cu combined with irradiation (IR) can induce ICD and exert anti-cancer effects in melanoma. In vitro experiments, treatment of MV3 and B16F10 melanoma cells with DSF/Cu + IR significantly increased the cellular apoptosis and increased ICD markers: damage-associated molecular pattern molecule (DAMP) exposure and release, including calreticulin cell surface expression, high-mobility group box 1 (HMGB1) release, and decreased intracellular ATP levels. In addition, DSF/Cu combined with IR treatment inhibited tumor growth and enhanced tumor-infiltrating immune cells in the B16F10-bearing C57BL/6 model. Our findings reveal that combining IR with DSF/Cu induces ICD and inhibits tumor growth in melanoma, providing a promising strategy to overcome the inherent resistance of RT in melanoma.

Germline genetic testing plays a critical role in diagnosing inherited predispositions and increasingly guides therapeutic and surveillance choices-but becomes technically challenging after allogeneic hematopoietic stem cell transplantation (HSCT), when donor-derived DNA contaminates host tissues. To address this, we compared donor-derived DNA across three accessible tissues-buccal swab, nail, and eyebrow follicles-in recipients after hematopoietic stem cell transplantation using two orthogonal assays (34-SNP next-generation sequencing and a 27-marker short tandem repeat panel) and modeled clinical covariates that influence chimerism. Eyebrow follicles showed consistently low donor DNA (median 1% by NGS; 3% by STR) whereas buccal swabs and nails carried substantially higher donor fractions (+25 and +22 percentage points versus eyebrow, respectively; both p < 0.01). Across methods, STR yielded on average ≈6 percentage points higher donor fractions than NGS at low-level chimerism. Several transplant covariates correlated with chimerism: matched-related donors and a perfect HLA match (10/10) were each associated with lower donor DNA (≈12-14 and 15-20 percentage points, respectively); longer times since hematopoietic stem cell transplantation correlated with lower levels for nail samples, and donor-recipient sex match correlated with higher donor DNA ( 7-8 percentage points). Even low-level chimerism can distort germline variant interpretation. We propose a pragmatic protocol for post-hematopoietic stem cell transplantation germline testing that prioritizes eyebrow follicles as the default tissue. An SNP-based quality control assay is used to flag unsafe donor fractions (≥ 5-10%) before comprehensive germline analysis, reducing the risk that chimeric donor DNA distorts germline variant interpretation.

Ovarian cancer is one of the deadliest gynecological malignancies, where most patients become clinically symptomatic at advanced stages of disease due to the lack of effective diagnostic screening. Despite recent advances in surgical resection and chemotherapy, recurrent ovarian cancer remains largely refractory to treatment, resulting in poor prognosis. The ovarian cancer tumor microenvironment (TME) is highly abnormal and presents a significant barrier to successful therapy. A combination of abnormal vasculature, desmoplastic extracellular matrix, and aberrantly activated hypoxic and immune-suppressive pathways culminates in promoting tumor growth, dissemination, chemoresistance, and immunosuppression. Whilst immune checkpoint inhibitors have shown success in other cancers, their application in ovarian cancer, particularly at advanced stages, remains limited. In this review, we discussed the application of tumor extracellular matrix normalizing therapies in preclinical models of advanced ovarian cancer, and their synergistic benefit to chemotherapy and immunotherapy. Collectively, these insights underscore TME normalization as a promising therapeutic strategy with the potential to improve ovarian cancer management.

Hepatic ischemia-reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent.

Atherosclerosis is a chronic, multifactorial vascular disease and the leading global cause of cardiovascular morbidity. Its development reflects interconnected disturbances in lipid metabolism, endothelial function, inflammation, smooth muscle cell (SMC) phenotypic switching, and extracellular matrix remodeling. Genetic predisposition, including monogenic disorders such as familial hypercholesterolemia and polygenic risk variants, modulates disease susceptibility by altering lipid homeostasis as well as inflammatory and thrombotic pathways. Epigenetic regulators and noncoding RNAs, such as histone modifications, microRNAs, and long noncoding RNAs, further shape gene expression and link environmental cues to vascular pathology. Endothelial injury promotes lipoprotein retention and oxidation, triggering monocyte recruitment and macrophage-driven foam cell formation, cytokine secretion, and necrotic core development. Persistent inflammation, macrophage heterogeneity, and SMC plasticity collectively drive plaque growth and destabilization. Emerging insights into immune cell metabolism, intracellular signaling networks, and novel regulatory RNAs are expanding therapeutic possibilities beyond lipid-lowering. Current and evolving treatments include statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, anti-inflammatory agents targeting interleukin-1 beta (IL-1β) or NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and advanced approaches such as gene editing, siRNA, and nanoparticle-based delivery. Integrating multi-omics, biomarker-guided therapy, and precision medicine promises improved risk stratification and next-generation targeted interventions. This review summarizes recent molecular advances and highlights translational opportunities for enhancing atherosclerosis prevention and treatment.

Airborne iodine-131 plays a pivotal role in both nuclear medicine and nuclear safety due to its radiotoxicity, volatility, and affinity for the thyroid gland. Although the total exhaled activity after medical I-131 therapy is minimal, over 95% of this activity appears in volatile organic forms, which evade standard filtration and reflect metabolic pathways of iodine turnover. Our experimental work in patients and mice confirms the metabolic origin of these species, modulated by thyroidal function. In nuclear reactor environments, both under routine operation and during accidents, organic iodides such as [131I]CH3I have also been identified as major airborne components, often termed "penetrating iodine" due to their low adsorption to conventional filters. This review compares the molecular speciation, environmental persistence, and dosimetric impact of airborne I-131 across clinical, technical, and accidental release scenarios. While routine reactor emissions yield negligible doses (<0.1 µSv/year), severe nuclear incidents like Chernobyl and Fukushima have resulted in significant thyroid exposures. Doses from these events ranged from tens of millisieverts to several Sieverts, particularly in children. We argue that a deeper understanding of chemical forms is essential for effective risk assessment, filtration technology, and emergency preparedness. Iodine-131 exemplifies the dual nature of radioactive substances: in nuclear medicine its radiotoxicity is therapeutically harnessed, whereas in industrial or reactor contexts it represents an unwanted hazard. The same physicochemical properties that enable therapeutic efficacy also determine, in the event of uncontrolled release, the range, persistence, and the potential for unwanted radiotoxic exposure in the general population. In nuclear medicine, exhaled activity after radioiodine therapy is minute but largely organically bound, reflecting enzymatic and metabolic methylation processes. During normal reactor operation, airborne iodine levels are negligible and dominated by inorganic vapors efficiently captured by filtration systems. In contrast, major accidents released large fractions of volatile iodine, primarily as elemental [131I]I2 and organically bound iodine species like [131I]CH3I. The chemical nature of these compounds defined their atmospheric lifetime, transport distance, and deposition pattern, thereby governing the thyroid dose to exposed populations. Chemical speciation is the key determinant across all scenarios. Exhaled iodine in medicine is predominantly organic; routine reactor releases are negligible; severe accidents predominantly release elemental and organic iodine that drive environmental transport and exposure. Integrating these domains shows how chemical speciation governs volatility, mobility, and bioavailability. The novelty of this review lies not in introducing new iodine chemistry, but in the systematic comparative synthesis of airborne radioiodine speciation across medical therapy, routine nuclear operation, and severe accident scenarios, identifying chemical form as the unifying determinant of volatility, environmental transport, and dose.