Anti-double-stranded DNA (anti-dsDNA) autoantibodies are detected in 20%-90% of patients with systemic lupus erythematosus (SLE), with prevalence varying according to disease activity, patient population, and assay methodology. Traditionally, four categories of anti-DNA autoantibodies have been described. The first recognizes only native dsDNA; the second recognizes both dsDNA and single-stranded DNA (ssDNA); the third reacts predominantly with denatured or ssDNA; and the fourth comprises anti-nucleosome autoantibodies, which recognize DNA-histone complexes and may yield results that differ from those obtained with assays specific for native dsDNA. Combining the Crithidia luciliae indirect immunofluorescence test with solid-phase immunoassays improves the diagnostic accuracy for anti-dsDNA antibody screening in patients with SLE. However, several limitations remain in the performance and interpretation of anti-dsDNA immassays, potentially leading to diagnostic errors. These pitfalls may arise mainly from analytical variability, assay design constraints, and a lack of standardized interpretation. Recent advances indicate a growing shift toward solid-phase multi-analyte arrays coupled with algorithm-based analysis, which may help reduce the seronegative gap in SLE while improving the harmonization of anti-dsDNA testing. This minireview critically evaluates current immunoassays for anti-dsDNA antibody testing, with particular emphasis on their analytical limitations, diagnostic pitfalls, and emerging advances.
BACKGROUND It has been reported that transforming growth factor beta (TGFβ) might play an important role for the development of various types of carcinomas. TGFβ is produced from not only cancer cells but also stromal cells such as fibroblasts. Controversial functions of TGFβ for tumor progression such as tumor suppression and progression has been widely recognized. TGFβ has 3 subtypes including TGFβ1, TGFβ2, and TGFβ3. The role of TGFβ1 and TGFβ3 for gastric carcinoma (GC) progression has been well-known, but that of TGFβ2 remains to be unknown. AIM To clarify the significance of TGFβ2 in the development of GC. METHODS Immunohistochemical analysis of GC was performed to clarify the clinical function of TGFβ2 on the progression of GC by evaluating TGFβ2 expression on both cancer cells and cancer-associated fibroblasts (CAFs) using 518 GC specimens. RESULTS High TGFβ2 expression in cancer cells was significantly correlated with T factor and stage, but not with vascular invasion and lymphatic invasion. In contrast, TGFβ2 expression on CAFs was significantly correlated with lymph node metastasis and vascular invasion, but not with the T factor. Five-year survival of patients with TGFβ2-high on cancer cells and -low on CAFs was significantly worse in compared to the other group These findings suggest that TGFβ2 might play differential roles between cancer cells and CAFs in the development of GC. CONCLUSION TGFβ2 on cancer cells might stimulates the cancer proliferation and invasion, but not TGFβ2 on CAFs. TGFβ2 high on cancer cells and low on CAF or others might be a promising prognostic factor for patients with GC.
The von Hippel-Lindau (VHL) protein, traditionally known for oxygen sensing via HIF-1α degradation, is now recognized as a multifunctional regulator of neural stem cell (NSC) fate and central nervous system regeneration. This review examines VHL’s role in lineage specification and its therapeutic potential. Under normoxia, VHL promotes rapid neuronal differentiation by suppressing JAK2/STAT and Notch signaling pathways. This relief of repression activates proneural bHLH factors like Neurogenin2 and Ascl1, leading to the generation of electrophysiologically mature, MAP2-positive neurons. Conversely, hypoxia-induced HIF-1α stabilization biases NSCs toward a glial fate, supporting survival and astrocytic differentiation in the injured environment. Beyond its canonical role, specialized modules expand VHL’s utility: The transferable BC-box motif can independently induce neuronal commitment in various somatic stem cells, while the Daam2-VHL-Nedd4 axis supports oligodendrocyte maturation and remyelination. Translational studies in models of Parkinson’s disease and spinal cord injury demonstrate that VHL-based strategies can achieve significant functional recovery. Understanding the context-dependent dynamics of VHL signaling is crucial for advancing regenerative therapies for neurodegenerative and demyelinating disorders.
BACKGROUND The pancreas is particularly vulnerable to rapid post-retrieval degradation due to its high endogenous RNase and enzymatic activity. This presents a major challenge in both pancreas research and clinical transplantation for accurate transcriptomic analyses. Accurate molecular profiling is increasingly important for evaluating graft quality and characterising injury. Although RNA preservation strategies have been reported in animal tissue studies, their comparative performance in human pancreatic tissue remains under-reported. AIM To evaluate biopsy preservation methods to validate an optimal approach capable of stabilising human-pancreas biopsies for high-quality gene expression analysis. METHODS Four clinically declined human pancreata were regionally sampled (36 biopsies per pancreas). Tissue was preserved using either: (1) Immediate RNA isolation; (2) Snap freezing; (3) RNAlater submersion; or (4) RNAlater injection. Immediate samples were extracted the same day with snap frozen and RNAlater samples being snap frozen and freeze-thawed prior to extraction using a spin-column protocol. RNA concentration and purity were assessed by Nanodrop and RNA integrity number (RIN) generated using a TapeStation. Statistical analyses were conducted using R-Studio. RESULTS All samples bar one yielded RNA of acceptable concentration (25-500 ng/μL) and purity (260/280 ~2.00, 260/230 2.00-2.2). RIN values varied significantly. Both RNAlater injection (7.1 ± 1.10; adjusted P value = 0.0089) and RNAlater submersion (7.1 ± 1.13; adjusted P value = 0.0058) produced significantly higher RIN scores compared to snap freezing (3.7 ± 1.21). RNAlater preserved samples exceeded the minimum RIN threshold for downstream transcriptomic analysis (RIN ≥ 7.0). No significant difference was observed between RNAlater techniques or immediate isolation (5.0 ± 1.18). CONCLUSION RNAlater based preservation by submersion or injection provided superior stabilisation of human pancreatic RNA compared with conventional snap freezing. RNAlater preserves the transcriptome at the moment of tissue acquisition, minimising degradation post biopsy. Despite the wide adoption of RNAlater usage, this study provides confirmation that RNAlater reliably supports high-quality RNA extraction from biopsies filling the current gap in pancreas-specific evidence. Implementation of this method may enable more accurate evaluation of graft injury, improve biomarker development, and support high-quality biobanking of human pancreas biopsies for future studies.
Coronary artery calcification is a common manifestation of advanced atherosclerosis and an important determinant of cardiovascular risk and procedural complexity during percutaneous coronary intervention (PCI). Calcification evolves from microcalcifications within the intima to larger fragmented, sheet-like or nodular deposits. Although extensive calcification often reflects stable plaque, specific patterns such as spotty calcification and eruptive calcified nodules are associated with plaque vulnerability and thrombotic events. In calcified lesions, PCI is technically challenging because calcium impairs balloon expansion, stent delivery and optimal stent deployment, increasing the risk of under-expansion and adverse outcomes. Intracoronary imaging with intravascular ultrasound and optical coherence tomography enables detailed calcium characterization and guides lesion preparation. This review summarizes the mechanisms, prevalence, risk factors, clinical consequences and contemporary management of calcified coronary artery disease.
Phytosterols are plant-derived sterols structurally similar to cholesterol and present in vegetable oils, seeds, legumes, and whole grains. Their best-established health effect is lowering circulating low-density lipoprotein cholesterol, mainly through inhibition of intestinal cholesterol absorption. Beyond this classical role, recent studies suggest that phytosterols may influence biological processes relevant to human health. Proposed mechanisms include changes in membrane lipid organization, modulation of nuclear receptors such as liver X receptors and peroxisome proliferator-activated receptors, activation of AMP-activated protein kinase, and regulation of metabolic and inflammatory signaling pathways. Experimental and human evidence indicates possible effects on adipose tissue function, hepatic lipid accumulation, insulin sensitivity, inflammation, oxidative stress, and immune responses. These findings have increased interest in the relevance of phytosterols to obesity, metabolic dysfunction-associated steatotic liver disease, type 2 diabetes, and immune-mediated disorders such as rheumatoid arthritis. Interactions with the gut microbiota and bile acid metabolism may provide additional pathways linking phytosterol intake with systemic effects, although human evidence remains limited. Antioxidant and anti-inflammatory actions have also been linked to neuroprotective and anticancer effects, but current support is mainly from preclinical studies. This review critically summarizes mechanistic and translational evidence, with emphasis on bioavailability, interindividual variability, safety, and remaining research gaps.
BACKGROUND:Tinospora cordifolia (T. cordifolia) Miers is an evergreen and dioecious herb of the Menispermaceae family. Senna siamea (S. siamea) Lam. is a medium-sized tree of the Fabaceae family, and it is known for its nutritional, economic, and medicinal importance. AIM:To analyze the phytochemicals and enzymes in T. cordifolia and S. siamea and perform an in vitro therapeutic assay. METHODS:The phytochemical compounds in T. cordifolia stem aqueous extract (TCAE), S. siamea leaf aqueous extract (SLAE), and S. siamea pod aqueous extract (SPAE) were estimated. Activity of catalase, superoxide dismutase, peroxidase, polyphenol oxidase, and ascorbate oxidase was quantified in protein extracts from T. cordifolia stem, S. siamea leaf, and S. siamea pods, and an in vitro therapeutic assay was performed in THP-1 cells. RESULTS:Quantitative analysis revealed that the total flavonoid content was high in SLAE. The total phenolic compound content was high in SLAE. The total tannin content was high in SPAE. The enzymatic activity of catalase, peroxidase, and ascorbate oxidase was high in T. cordifolia stem, and the enzymatic activity of superoxide dismutase and polyphenol oxidase was high in S. siamea pods. TCAE, SLAE, and SPAE induced THP-1 cell apoptosis due to an increase in reactive oxygen species and a decrease in mitochondrial membrane potential activity. CONCLUSION:T. cordifolia and S. siamea may have therapeutic potential in leukemia, but further clinical studies are needed.
BACKGROUND:Oxidative stress has been suggested to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM) and development of complications by altering antioxidant levels and inducing lipid peroxidation. Although patients with T2DM are reported to be under oxidative stress because of prolonged exposure to hyperglycemia, the influence of glycemic control in diabetes on enhanced free-radical activity is poorly understood. AIM:To evaluate the levels of malondialdehyde (MDA) - a marker of lipid peroxidation and catalase (CAT) - an antioxidant enzyme in patients with T2DM categorized by glycemic control, and to compare these levels with those of apparently healthy individuals in Buea, Cameroon. METHODS:A hospital-based case-control study was conducted at Buea Regional Hospital from January 2024 to June 2024 involving patients with T2DM and age-matched healthy controls. Socio-demographic, clinical and anthropometric data were collected using a structured questionnaire. Levels of glucose, lipid profile, CAT and MDA were determined by spectrophotometry. Glycated hemoglobin was measured using ion exchange high performance liquid chromatography method. Data analyses were done using IBM SPSS version 26.0 for Windows. A P ≤ 0.05 was considered statistically significant. RESULTS:A total of 192 participants (96 patients with T2DM and 96 healthy controls) were recruited in this study. The mean age of the participants was were 47.97 ± 10.3 years with most being males (62.5%). CAT activity and high-density lipoprotein cholesterol levels were higher in control subjects (P < 0.05). The majority of patients with T2DM (80.2%) had a poor glycemic control. CAT activity was lower and MDA was significantly higher in patients with T2DM with poor glycemic control (P < 0.001). Glycated hemoglobin showed a significantly strong positive correlation with MDA levels (r = 0.846, P < 0.001) and a significantly strong negative correlation with CAT activity (r = -0.567, P < 0.001). Additionally, there was a significant negative correlation between CAT activity and MDA (r = -0.568, P < 0.001). CONCLUSION:The results of this study indicated a significantly higher level of MDA and lower CAT activity in patients with T2DM compared to apparently healthy age-matched and sex-matched controls. Increased lipid peroxidation and decrease antioxidant enzyme activity were associated with poor glycemic control. The correlation between lipid peroxidation, antioxidant activity, and glycemic control highlights the role of oxidative stress in the pathophysiology of T2DM.
Forensic deoxyribonucleic acid (DNA) interpretation is limited less by genotyping technology than by the biochemical and inferential effects of mixed, low-template, and environmentally complex traces. Single-cell and single-molecule strategies, including the United Kingdom Research and Innovation-funded single-cell and single-molecule analysis for DNA identification (SCAnDi) program, aim to preserve cellular resolution. They allow investigators to isolate and type individual cells or defined small-cell pools before heterogeneous evidence is converted into a bulk lysate. In selected validation settings, this approach has yielded near-complete diploid short tandem repeat (STR) profiles from small pools, credible genotype sets tightly concentrated on the true genotype across high-order mixtures, and improved access to donor-specific profiles from sexual assault and other complex samples. However, these studies also show important limits. Many operationally successful “single-cell” workflows are, in practice, single-cell-plus-consensus or few-cell workflows. Stochastic effects remain intrinsic, and cell capture itself becomes a probabilistic sampling step. This opinion review explicitly adopts an evaluative stance: It synthesizes recent validation studies and guidance documents to identify the performance thresholds and reporting boundaries that should be met before targeted forensic deployment of SCAnDi-like workflows. We argue that casework entry should require measured cell-recovery probabilities, phenotype-misclassification rates, locus- and cell-type-specific dropout and stutter models, quantified contamination and drop-in rates, validated minimum cell counts for consensus generation, and explicit database-upload criteria. It should also require strict separation between sub-source reporting and activity-level propositions. If those conditions are met, single-cell typing can complement, rather than replace, bulk STR analysis and probabilistic genotyping in a narrow but important set of high-value forensic scenarios.
Obesity, a global epidemic, is closely linked to metabolic complications like insulin resistance and type 2 diabetes. Pancreatic dysfunction (impaired islet secretion and local inflammation) is central to this deterioration, yet the underlying mechanisms remain unclear. Pancreatic macrophages regulate tissue inflammation and metabolic homeostasis, but their context-specific polarization in obesity is undefined. This review discusses the role of triggering receptor expressed on myeloid cells 2 (TREM2) in modulating pancreatic macrophage behavior in the context of obesity, based on findings from diet-induced obese mouse models and ex vivo pancreatic analyses. Emerging evidence indicates that TREM2 expression is markedly upregulated in pancreatic macrophages of obese subjects, where TREM2-driven macrophage activation promotes pro-inflammatory cytokine release and disrupts macrophage-islet β-cell crosstalk. Transcriptomic profiling reveals that TREM2 signaling reshapes macrophage transcriptional landscapes, enhancing pro-inflammatory phenotypes while impairing islet-supporting capacity. Notably, macrophage-specific TREM2 ablation has been shown to ameliorate pancreatic inflammation, restore islet insulin secretion, and alleviate systemic metabolic disorders in obese mice. Collectively, these findings identify TREM2 as a pivotal molecular switch governing pancreatic macrophage-mediated metabolic dysfunction in obesity, highlighting TREM2+ pancreatic macrophages as a potential therapeutic target. These findings advance the understanding of immune-metabolic crosstalk in the pancreas, laying a foundation for developing novel immunometabolic interventions.
Hepatitis B virus (HBV) reactivation after targeted therapy or immunomodulating therapy leads to active or fulminant hepatitis, low response to prophylactic vaccination, premature discharge from therapy and death. The hypothesis that seroreactive viral infection is caused by mutation/s in the precore/core is invaluable to elucidating the mechanisms of HBV reactivation. Precore/core mutations may correlate with, or predict susceptibility to seroreactivation in HBV-related hepatocellular carcinoma (HCC) patients receiving targeted therapy. This review's objective is to re-analyze the relationship between the precore/core mutations of HBV-DNA and HBV reactivation in HCC patients receiving targeted therapy. Further, to re-analyze clinically significant precore/core mutations affecting pregenomic RNA initiation and synthesis, and their regulation of viral and cellular gene expressions. This review shed light on the mechanism of HBV reactivation. We analyze the effects of antivirals lamivudine, entecavir, tenofovir alafenamide, tenofovir disoproxil fumarate and immune-based strategies on reactivation after treatment for HBV-related HCC. We proposed future directions for studying mutations in the precore/core region that are likely to cause relapse. This review recommends comparing the genome/proteome of blood from overt and relapsed HCC-related chronic HBV patients. This helps identifying persistent genetic/epigenetic profiles of HBV resistant variants, thus accurately selecting the appropriate antiviral therapy and eliminating the risk of viral reactivation.
Choline supports phospholipid synthesis, membrane integrity, neurotransmission, verylowdensity lipoprotein export, and one-carbon/epigenetic pathways, yet most United States adults fall short of adequate intake. Fatty liver is now viewed as a mitochondrial-centric metabolic-inflammatory disorder; ethanol and excess linoleic acid (LA) can magnify bioenergetic stress when choline is insufficient to sustain phosphatidylcholine/phosphatidylethanolamine. This narrative review examines whether optimized choline delivery, alongside reduced exposure to mitochondrial toxicants, offers a rational therapeutic approach. Low choline intake associates with higher liver fat and aminotransferases. In rodents, choline deficiency combined with ethanol or LA lowers mitochondrial membrane potential, limits β-oxidation, and promotes steatosis and inflammation. Advanced formulations-especially citicoline-demonstrate favorable absorption and tissue choline delivery and may lessen trimethylamine-N-oxide formation versus free choline salts. Early, small human studies suggest that choline repletion, together with curtailed ethanol or dietary LA, can reduce intrahepatic triglyceride content and improve insulin sensitivity, though large randomized trials are lacking. Framing fatty liver as nutrition-modifiable mitochondrial toxicosis highlights correctable choline insufficiency when the liver is burdened by ethanol or excess LA. A dual strategy-using higher-bioavailability, gutmicrobial trimethylamineNoxide-sparing choline forms and mitigating mitochondrial toxicants-targets core bioenergetic defects, may reverse early steatosis, and warrants testing in adequately powered clinical trials.
Pentadecanoic acid (C15:0) is an odd-chain fatty acid, the β-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux; higher circulating levels are associated with reduced type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, and mortality. Summarize the cellular and molecular mechanisms underlying these associations. A comprehensive literature search (2000-2025) identified studies of C15:0's mechanistic actions in vitro and in vivo, and multi-omics studies focused on receptor binding, signaling cascades, gene expression, and comparative pharmacology. C15:0 is a dual partial peroxisome proliferator-activated receptor α/δ agonist. It activates AMP-activated protein kinase, suppresses mechanistic target of rapamycin, and selectively inhibits histone deacetylase 6. It augments succinate-driven complex II respiration, preserves mitochondrial membrane potential, limits reactive oxygen species, and attenuates interleukin-6 (IL-6) - triggered Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B p65 signaling, lowering monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and IL-6. Across the BioMAP® human-primarycell platform - which tests 12 distinct primary human cell systems such as endothelial cells, fibroblasts, macrophages, and T-cells - C15:0 (17 µM) produced statistically significant changes in 36 mechanistically diverse biomarkers. This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. C15:0 engages receptor targets that converge on enhanced lipid oxidation, cellular energetics, and inflammation resolution. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.
BACKGROUND:Alzheimer's disease is a neurodegenerative dementia characterized by accumulation of β-amyloid plaques, tau hyperphosphorylation, and neuroinflammation. Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration, particularly the involvement of Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis. Experimental mouse models have been used to explore how P. gingivalis products contribute to neuroinflammatory and degenerative processes. However, a comprehensive synthesis of these findings is lacking. This systematic review evaluates the role of P. gingivalis-derived factors in triggering Alzheimer's-like pathology, with an emphasis on bacterial products and host immune responses. We hypothesize that P. gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease. AIM:To link gingival P. gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models. METHODS:This systematic review followed the 2020 PRISMA guidelines. A comprehensive search was conducted in five databases (PubMed, Scopus, ScienceDirect, Sage, SpringerLink) for original studies between 2014 and 2024. Studies included mouse models to evaluate the effect of P. gingivalis or its products on Alzheimer's-like pathologies. Exclusion criteria were in vitro, human, or review studies. Twenty-three studies met the inclusion criteria. Bacterial components and activated host factors were extracted, categorized, and analyzed using narrative synthesis and descriptive statistics. RESULTS:In 24 studies, lipopolysaccharides (54.84%) and gingipains (25.81%) were the most frequently reported P. gingivalis products. These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines. The host response included β-amyloid accumulation, Tau hyperphosphorylation, and changes in blood-brain barrier permeability. Glial cells were the most frequently mentioned host factors (n = 15), followed by proteins (n = 13) and cytokines (n = 11). These interactions promoted cognitive impairment, synaptic dysfunction, and neurodegeneration in mouse models, supporting a role for P. gingivalis in Alzheimer's-like pathology. CONCLUSION:P. gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models, supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
The canonical signaling of interferon gamma (IFN-γ) through the Janus kinase 1 and 2–signal transducer and activator of transcription 1 (STAT1) axis leads to the expression of several interferon-stimulated genes (ISGs), which have diverse effects depending on the cellular context. In glioblastoma, a highly aggressive primary brain tumor in adults, elements of IFN-γ canonical signaling are deregulated, resulting in the overexpression of STAT1-target ISGs associated with tumor progression. This mini-review highlights key ISGs, including STAT1 , interferon regulatory factor 1, programmed death-ligand 1, indoleamine 2,3-dioxygenase 1, and interferon-stimulated gene 15, involved in the pathology of glioblastoma. These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γ signaling in this malignancy.
BACKGROUND:Neurodegeneration refers to the progressive loss of neurons, affecting both their structure and function. It is driven by synaptic dysfunction, disruptions in neural networks, and the accumulation of abnormal protein variants. Endoplasmic reticulum (ER) stress, caused by the accumulation of misfolded or unfolded protein, is a major contributor to neurodegeneration. Dithiothreitol (DTT) is a widely used redox reagent that disrupts the oxidative protein folding environment, inducing ER stress and leading to the imbalance in protein homeostasis can activate stress response pathway, potentially contributing to neurodegenerative processes. Caenorhabditis elegans (C. elegans) is a widely used model organism for studying neurodegeneration due to its well-mapped nervous system, approximately one-third of neuron cells in their body, complete genome sequenced, and conserved stress response pathway. AIM:To study the neurodegeneration in C. elegans caused by DTT-induced ER stress, assessed by behavioral, molecular, and lifespan changes. METHODS:C. elegans were cultured on nematode growth medium plates with OP50, and ER stress was induced using DTT. Effects were assessed via behavioral assays such as locomotion, chemotaxis, lifespan assay, and molecular studies. RESULTS:DTT exposure led to a significant decline in locomotion and chemotaxis response, indicating neurotoxicity. A reduction in lifespan was observed, suggesting an overall impact on health. Molecular analysis confirmed ER stress activation. DTT-induced ER stress negatively affects C. elegans, leading to behavioral impairments and molecular alterations associated with neurodegeneration. CONCLUSION:These findings establish C. elegans as a potential model for studying ER stress-mediated neurotoxicity and its implications in neurodegenerative diseases.
Obesity is a major contributor to metabolic dysfunction, and its impact on pancreatic health has garnered increasing attention. Macrophages, as key regulators of inflammation and metabolism, play a central role in mediating obesity-induced pancreatic damage. In obese individuals, excessive lipid accumulation and chronic low-grade inflammation drive the infiltration and polarization of macrophages within the pancreas. These macrophages, particularly the pro-inflammatory Macrophage, pro-inflammatory phenotype (M1) phenotype, secrete cytokines such as C-C motif ligand 2 (CCL2) and transforming growth factor beta (TGF-β), which disrupt pancreatic β-cell function and impair insulin secretion. Conversely, anti-inflammatory Macrophage, anti-inflammatory phenotype (M2) macrophages contribute to tissue repair but may also promote fibrotic changes under prolonged metabolic stress. Pancreatic macrophages are activated under high-fat diet conditions, promoting inflammation and impairing β-cell function through the SUCLA2-HIF-1α axis and mechanistic Target of Rapamycin Complex 1 (mTORC1)/PD-1 pathway, thereby establishing a self-perpetuating "metabolic-immunosuppressive" vicious cycle. Targeted intervention strategies against macrophages-such as SUCLA2 inhibitors can ameliorate metabolic dysregulation. Meanwhile, exosome-mediated interorgan communication [e.g., via microRNA-155 (miR-155) and miR-30a] offers novel insights for multi-system synergistic therapies. Understanding the mechanisms by which macrophages mediate metabolic dysregulation in the pancreas under obese conditions provides critical insights into the pathogenesis of obesity-related pancreatic disorders.
BACKGROUND:Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy, limiting treatment efficacy and worsening patient outcomes. Recent studies have implicated the gut microbiome and its key metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), in mediating inflammation, oxidative stress, and cardiac damage. The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction. AIM:To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients. METHODS:A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2013 and December 2024. Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition, microbial metabolites (e.g., SCFAs, TMAO), or microbiome-targeted interventions. Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction focused on microbiota alterations, mechanistic pathways, cardiac outcomes, and quality assessments using standardized risk-of-bias tools. RESULTS:Eighteen studies met the inclusion criteria. Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains. This imbalance contributed to gut barrier disruption, systemic inflammation, and oxidative stress, all of which promote myocardial damage. SCFA depletion weakened anti-inflammatory responses, while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction. Preclinical studies showed promising cardioprotective effects from probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, though human data remain limited. CONCLUSION:Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity. Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury. Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology, warranting further clinical validation through well-designed trials.
