Biomedical Journal最新文献

Background: Major Depressive Disorder (MDD) is increasingly viewed through the lens of the neuroinflammatory hypothesis and gut-brain axis dysfunction. Short-Chain Fatty Acids (SCFAs), the primary metabolites produced by the gut microbiota, are vital signaling molecules that maintain intestinal barrier integrity, modulate peripheral immunity, and influence microglial function. While individual studies suggest altered SCFAs levels in MDD, a definitive, quantitative synthesis establishing a robust biomarker signature is currently lacking. This meta-analysis aimed to precisely characterize the signature of SCFAs (acetic, propionic, butyric, and isobutyric acid) in MDD patients compared to healthy controls.

Methods: We systematically searched major databases across PubMed, Embase, and Web of Science databases for studies quantifying SCFAs levels up to September 15, 2025. Studies examining SCFAs levels in depressed patients and depressive-like murine models, as well as studies investigating SCFAs interventions for depressive-like behavior, were selected for synthesis. Risk of bias was evaluated using the Newcastle-Ottawa Scale. The effect sizes were synthesized using a random-effects model and presented as standardized mean differences.

Results: Eight human and 52 murine studies were included in the meta-analyses. Depressed patients showed significantly lower concentrations in blood (plasma and serum) of propionic (SMD = -0.60, p-value = 0.007), butyric (SMD = -0.50, p-value = 0.006), isobutyric (SMD = -0.72, p-value = 0.020), valeric (SMD = -0.43, p-value = 0.040) and isovaleric acids (SMD = -0.75, p-value = 0.002). Secondary analysis of MDD patients confirmed consistent reductions. High heterogeneity was observed. In murine models, SCFAs depletion was frequently observed, while supplementation improved depressive-like behaviors.

Conclusion: MDD is characterized by a significant, quantifiable deficit in the circulating SCFAs metabolome, which provides strong empirical validation for the gut-brain axis hypothesis in depression. We advocate for the investigation of SCFAs as novel, measurable peripheral biomarkers and targeted therapeutic agents (e.g., butyrate supplementation) for precision nutritional psychiatry.

This issue brings together reviews and original research addressing diverse aspects of immune regulation, disease mechanisms, and clinical management. Several reviews focus on macrophages as integrative regulators across physiological systems, including their circadian control of immune activity, their role in coordinating endocrine signaling within the hypothalamic-pituitary axes, and their functions in cardiac tissue homeostasis and repair. Additional contributions revisit the development of regulatory T cells as a central mechanism of peripheral immune tolerance, examine the potential of artificial intelligence for infectious disease surveillance, and discuss emerging roles of long non-coding RNAs in cardiac regeneration. Further reviews evaluate multidisciplinary care strategies for pelvic floor disorders and analyze the inflammatory consequences of photodynamic therapy. Original studies in this issue investigate areca nut-associated head and neck carcinogenesis, determinants of persistent carbapenem-resistant Klebsiella pneumoniae bacteremia, treatment outcomes in hepatocellular carcinoma with portal vein tumor thrombus, protective effects against gastric ulceration, machine-learning-assisted interpretation of syphilis serology, and relapse patterns following orthognathic surgery.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its broad-spectrum antimicrobial resistance and capacity for horizontal gene transfer.

Methods: Three clinical CRKP isolates, each carrying one of the three major classes of carbapenemase as class A (bla_KPC), class B (bla_NDM), and class D (bla_OXA) were selected. A CRISPR/Cas9-based system (pCasKP-pSGKP) was employed to target carbapenem resistance genes in these strains (KP21040 with bla_OXA-181, KP4-78 with bla_NDM-1, and KP5-4 with bla_KPC-2).

Results: CRISPR/Cas9-mediated editing led to partial reduction or complete loss of resistance plasmids, as evidenced by S1 nuclease-pulsed-field gel electrophoresis. This plasmid elimination correlated with a marked restoration of susceptibility to ertapenem, showing a greater than 64-fold reduction in minimum inhibitory concentrations (MICs) across all strains. In KP21040, MICs for ertapenem and levofloxacin decreased to 0.006 μg/mL and 0.125 μg/mL, respectively. Whole-genome analysis revealed that bla_OXA-181 was flanked by insertion sequence (IS)26 elements, which mediated homologous recombination upon CRISPR-induced double-strand breaks, resulting in excision of a ∼15 kb segment including bla_OXA-181 and qnrS1. These findings suggest that ISs may enhance CRISPR efficacy by promoting recombination-driven deletion. Moreover, the complete removal of all three resistance plasmids was observed in the KP5-4 strain harboring bla_KPC-2.

Conclusion: This study demonstrates that CRISPR/Cas9-based genome editing can eliminate plasmid-encoded carbapenemase genes in clinical CRKP isolates and, in specific genetic contexts, facilitate the concurrent removal of associated quinolone resistance determinants. These findings support CRISPR-based genome editing as a proof-of-concept strategy for addressing plasmid-mediated multidrug resistance in Gram-negative pathogens.

The rising threat of antimicrobial resistance has underscored the urgent need for rapid, standardized, and automated antimicrobial susceptibility testing (AST) solutions. Leveraging recent advances in computer vision and deep learning, this study introduces a fully image-based diagnostic framework that integrates a YOLOv8n object detection model with a Convolutional Neural Network (CNN) to perform end-to-end bacterial identification and susceptibility classification directly from Petri dish images. The YOLOv8n model accurately localizes handwritten bacterial species labels with a mean Average Precision (mAP@0.50) exceeding 0.93, demonstrating robustness across diverse handwriting styles and imaging conditions. Complementarily, the CNN achieves a balanced accuracy of 94.7% and 100% sensitivity for susceptible cases by analyzing inhibition zone morphology without manual measurements or interpretive rules. Notably, the system achieved a 0% Very Major Error (VME) rate, ensuring no resistant isolates were misclassified as susceptible. The dual-model system generalizes effectively across experimental variations and produces high-confidence predictions, highlighting its potential to streamline AST workflows, minimize human variability, and enhance diagnostic reliability in clinical microbiology.

Hepatitis D virus (HDV) infection represents a major global public health challenge and is responsible for the most severe form of chronic viral hepatitis. Affecting an estimated 12 million individuals worldwide, chronic hepatitis D is associated with rapid progression to advanced liver disease, including cirrhosis and hepatocellular carcinoma. Despite its clinical burden, therapeutic options for HDV remain limited. In this context, pegylated interferon alpha (PEG-IFN-α) continues to be the most widely used treatment globally, particularly outside Europe where access to newly approved therapies is restricted. However, PEG-IFN-α is characterized by modest and heterogeneous antiviral efficacy, frequent viral relapse, and a high rate of adverse effects, highlighting the need for improved therapeutic strategies. A better understanding of the mechanisms underlying interferon responsiveness and resistance in HDV infection is therefore essential. The complex interplay between HDV and the innate immune response plays a central role in determining viral persistence and treatment outcome. HDV is sensed by innate immune receptors and induces type I and type III interferon responses, yet these responses are insufficient to control viral replication. Viral nuclear replication, interferon-stimulated gene accessibility, and active interference with interferon signaling pathways contribute to the limited antiviral activity of interferons against HDV. This review synthesizes current knowledge on the interactions between HDV and the interferon response, discusses experimental models used to study these mechanisms, and highlights key limitations and open questions that must be addressed to optimize future interferon-based and combination therapies.

Background: Eye care is crucial for patients with mental disorders, yet it is often overlooked. Previous studies suggest a link between mental disorders and dry eye disease, but results on objective tear function are inconsistent. This meta-analysis aimed to compare tear function between patients with and without mental disorders.

Methods: We systematically searched Embase, PubMed, Cochrane and PsycINFO up to November 19, 2025. We included studies reporting the comparison of tear function outcomes measured by the Schirmer test or tear break-up time (TBUT) between adult patients with and without mental disorders. The meta-analysis based on a random-effects model presented pooled mean differences between groups.

Results: We included 15 studies with a total of 3,319 participants. Our meta-analysis revealed that patients with mental disorders had lower TBUT (MD: -3.72, 95% CI: -5.76 to -1.69, I²: 99%) and Schirmer test (MD: -4.62, 95% CI: -7.42 to -1.83, I²: 98%). Results remained consistent across subgroup analyses based on gender, study country, psychiatric diagnosis, psychiatric medication use and study design. Notably, significantly lower Schirmer test results were observed even in patients not receiving psychiatric medication.

Conclusion: Compared to patients without mental disorders, patients with mental disorders were associated with poor tear function. Regular monitoring and early detection of tear dysfunction should be considered for patients with mental disorders. However, due to the substantial heterogeneity and the cross-sectional design of most included studies, the findings should be interpreted with caution and are best viewed as hypothesis-generating.

Short-term systemic corticosteroids are widely prescribed to treat acute flare-ups of chronic immunologic diseases or to manage acute inflammatory conditions such as allergic reactions, skin disorders, and respiratory infections. This review revisits the safety of short-term systemic corticosteroids, focusing on emerging evidence of their potential unexpected risks. Epidemiological studies reveal an increasing trend in the prescribing of short-term systemic corticosteroids to the general population. However, concerns have been raised regarding the safety of short-term oral corticosteroids, with recent evidence suggesting that even brief courses are associated with rare but serious adverse events, including sepsis, pneumonia, gastrointestinal bleeding, acute pancreatitis, heart failure, venous thromboembolism, and fracture. Recent studies also highlight long-term risks of antenatal corticosteroids. While crucial for reducing neonatal respiratory distress syndrome in pregnancies at risk of preterm delivery, antenatal corticosteroids are linked to long-term risks of neuropsychiatric disorders, serious infections, and even mortality in children, along with heightened risks of infections, heart failure, and gastrointestinal bleeding in mothers. These findings suggest the potential harms of short-term systemic corticosteroids may have been previously underrecognized. Raising awareness of these risks can help clinicians balance therapeutic benefits with potential harms and ensure safer clinical practice. Cautious and evidence-based approaches to prescribing short-term systemic corticosteroids are necessary, particularly in vulnerable populations. Further research is needed to develop a "corticosteroid stewardship" approach that promotes prescribing systemic corticosteroids only for appropriate indications, minimizes unnecessary use, and encourages careful monitoring of adverse effects to optimize patient outcomes.

Background: Depression is a multifactorial neuropsychiatric disorder linked to neuroinflammation and epigenetic dysregulation, particularly in histone acetylation. Although magnolol has demonstrated antidepressant-like properties, its precise molecular mechanisms remain unclear. This study aimed to evaluate the antidepressant effects of magnolol and its influence on epigenetic regulation of synaptic plasticity in a chronic unpredictable mild stress (CUMS) mouse model.

Material and methods: C57BL/6 mice subjected to CUMS were treated orally with magnolol. Depressive-like behaviors were assessed using standard behavioral tests. Expression levels of histone deacetylase 2 (HDAC2), synaptic proteins such as neuroligin-1 (NLGN1) and neurexin-1β (NRXN1β), and their associated co-localized puncta were examined. Golgi staining and immunofluorescence were performed to assess dendritic spine density and DCX-positive cell population in the hippocampus.

Results: Magnolol treatment alleviated depressive-like behaviors, evidenced by increased sucrose preference and reduced immobility in behavioral assays. It also attenuated hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as shown by normalization of serum corticosterone levels and restoration of glucocorticoid receptor (GR) expression in the hippocampal CA1 region. At the molecular level, magnolol reduces HDAC2 expression, which may be associated with altered histone acetylation, thus upregulation of NLGN1 and NRXN1β, enhancing the formation of pre- and postsynaptic co-localized puncta. Additionally, magnolol promoted hippocampal DCX-positive cell population and synaptogenesis, supporting improvements in structural and functional neuroplasticity.

Conclusion: Our findings demonstrate the ability of magnolol to modulate histone acetylation and synaptic architecture involved in its antidepressant-like action. These results provide a foundation for further exploration of magnolol-based interventions targeting epigenetic and synaptic mechanisms in depression.

The 2025 Nobel Prize in Physiology or Medicine, awarded to Shimon Sakaguchi, Mary E. Brunkow, and Fred Ramsdell, recognizes the discovery and molecular definition of regulatory T cells (Tregs) as the cornerstone of peripheral immune tolerance. This recognition honors a transformative journey marked by Sakaguchi's identification of CD4⁺CD25⁺ T cells as a regulatory population (1995), followed by Brunkow and Ramsdell's discovery that mutations in the FOXP3 gene cause both the scurfy mouse phenotype and human IPEX syndrome (2001), and culminating in the demonstration that FOXP3 governs Treg development and function (2003). This achievement crowns a turbulent half-century arc. The suppressor T-cell (Ts) hypothesis of the 1970s proposed an active T-cell brake on immunity but collapsed in the 1980s due to phenotypic ambiguity and reproducibility failures. Following this "dark age," the concept of active suppression was kept alive through functional studies in organ-specific autoimmunity (Parish, Kong, Rose) and transplantation tolerance (Waldmann). However, it was Sakaguchi's discovery of CD25 as a specific marker that finally provided the physical identity of these cells, bridging the gap between functional observation and cellular definition. The subsequent identification of FOXP3 as the lineage-defining transcription factor transformed a disputed concept into a reproducible, engineerable immune module. Today, this molecular precision drives broad clinical translation, ranging from Treg-based therapies in autoimmunity and transplantation to targeted Treg modulation in cancer immunotherapy. This Short Review traces the trajectory-from controversy to molecular definition-and frames a forward path for context-dependent modulation of Tregs in clinical medicine.

Background: Aging is associated with impaired muscle protein turnover, oxidative stress, and functional decline. Both renin-angiotensin system (RAS) inhibition and exercise modulate redox balance and anabolic-catabolic signaling; however, how aging influences their effects under physiological conditions remains unclear.

Methods: Middle-aged (50 weeks) and old (72 weeks) female C57BL/6 mice were randomly assigned to control (C), losartan (L; RAS inhibitor), exercise (E), or combined losartan plus exercise (LE) groups for a four-month intervention. Exercise capacity, cardiac function, oxidative stress markers [thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC)] in skeletal muscles, and key regulators of muscle protein turnover (Akt, mTOR, ERK1/2, Smad2, FoxO3a, and p38 MAPK) were evaluated. Two-way analysis of variance was used to determine whether age influences the effects of interventions.

Results: Exercise training (E and LE) improved exercise capacity in both age groups. The combined LE intervention significantly enhanced cardiac systolic function compared to exercise alone. Losartan exerted age-dependent, opposite redox effects. In middle-aged mice, losartan increased TBARS and reduced TAC. Conversely, in old mice, losartan significantly reduced TBARS and increased TAC. Most protein turnover regulators (Akt, mTOR, ERK, FoxO3a, and p38 MAPK) remained unchanged by interventions, while Smad2 activation exhibited age-dependent patterns. Smad2 activation levels increased in middle-aged LE mice but were reduced by exercise in old mice.

Conclusions: While exercise is a robust intervention, losartan's efficacy is critically dependent on the animal's baseline oxidative status. These findings highlight the importance of considering age as a critical factor when designing pharmacological interventions for age-related muscle atrophy.