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Volume 12 ， Issue 4 ， 2025
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P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasiavia IL-6/IL-6R pathway AI Introduction“In the field of benign prostatic hyperplasia (BPH), a study led by experts has explored the role and mechanism of Porphyromonas gingivalis (P. gingivalis) in the development of BPH. The research found that P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.”
Abstract：Background:Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.Methods:The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.Results:P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Sp and Pf in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97-fold and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81-fold and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.Conclusion:P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.Keywords：Porphyromonas gingivalis (P. gingivalis);Benign prostatic hyperplasia (BPH);Periodontitis;Oral pathogens;Inflammation57|0|0Updated：2025-12-13 -
Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers AI Introduction
“In the field of cancer research, a comprehensive analysis of enhancer RNA quantitative trait loci (eRNAQTLs) was conducted, identifying 300,112 eRNAQTLs across 30 cancer types. Expert established the CancereRNAQTL system, which provides solutions to solve cancer heritability problems and lays a foundation for the construction of eRNA-based therapeutic strategies.”
Abstract：Background:Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, largescale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR=0.91, 95%CI 0.88–0.95, P=2.92×10−7) and Europe (OR=0.92, 95%CI 0.88–0.95, P=4.61×10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL (http://canernaqtl.whu.edu.cn/#/) to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.Keywords：Enhancer RNA (eRNA);eRNA quantitative trait loci (eRNAQTLs);Genome-wide association study (GWAS);ENSR00000155786;SENP735|0|0Updated：2025-12-13 - “Reporting on the cutting-edge research in rapid antidepressant mechanisms, a study delves into the role of the neuropeptide PACAP in mediating swift responses to depression treatment. The research, involving 446 mice and various behavioral and molecular assays, reveals that activating hippocampal PACAP signaling triggers a rapid antidepressant effect by modulating CaMKⅡ inhibition-governed eEF2-mTOR-BDNF signaling, offering a new therapeutic approach for depression.”
Abstract：Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression, but the underlying cellular and molecular mechanisms remain unclear. Implicated in depression regulation, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms. The signaling mechanism of PACAP in the hippocampal dentate gyrus (DG) was evaluated by utilizing site-directed gene knockdown, pharmacological interventions, or optogenetic manipulations. Overall, 446 mice were used for behavioral and molecular signaling testing. Mice were divided into control or experimental groups randomly in each experiment, and the experimental manipulations included: chronic paroxetine treatments (4 d, 9 d, 14 d) or a single treatment of ketamine; social defeat or lipopolysaccharides-injection induced depression models; different doses of PACAP (0.4 ng/site, 2 ng/site, 4 ng/site; microinjected into the hippocampal DG); pharmacological intra-DG interventions (CALM and PACAP6-38); intra-DG viral-mediated PACAP RNAi; and opotogenetics using channelrhodopsins 2 (ChR2) or endoplasmic natronomonas halorhodopsine 3.0 (eNpHR3.0). Behavioral paradigms included novelty suppressed feeding test, tail suspension test, forced swimming test, and sucrose preference test. Western blotting, ELISA, or quantitative real-time PCR (RT-PCR) analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression, and intra-DG blockade of PACAP attenuated the onset of the antidepressant response. The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors. Conversely, a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice. Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses, while optogenetic inhibition induced depression-like behaviors. The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses. Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ)-eukaryotic elongation factor 2 (eEF2) and activating the mammalian target of rapamycin (mTOR). Pre-activation of CaMKⅡ signaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor (BDNF) signaling. Finally, acute ketamine treatment upregulated hippocampal PACAP expression, whereas intra-DG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡ inhibition-governed eEF2-mTOR-BDNF signaling.Keywords：Antidepressant response;Pituitary adenylate cyclase-activating polypeptide (PACAP);Ketamine;Optogenetic;Novelty suppressed feeding (NSF)37|0|0Updated：2025-12-13
RESEARCH
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Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine AI Introduction
“In the field of aging and regeneration research, spatiotemporal multi-omics approaches have made significant progress. Expert researchers have established the spatiotemporal multi-omics system, which provides solutions to solve the problems of molecular dynamics, cellular interactions, and signaling pathways in aging and regeneration research.”
Abstract：Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.Keywords：Spatiotemporal multi-omics;Aging and regeneration;Cellular interactions;Innovative therapeutic strategies32|0|0Updated：2025-12-13 - “In the field of gut microbiome research, advancements in isolation and cultivation techniques such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion have been made. Expert xx established the xx system, which provides solutions to solve the problem of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms.”
Abstract：The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.Keywords：Gut microbes;Culturomics;Microbial identification;Droplet microfluidics;Strain-level investigation24|1|0Updated：2025-12-13 -
Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives AI Introduction
“Reporting on the latest research in the field of neuroendocrine neoplasms, this review highlights the limitations and recent advancements in understanding the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of gastroenteropancreatic NENs, which provides solutions to solve the delays in diagnosis and timely treatment of these patients.”
Abstract：Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic NENs (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.Keywords：Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs);Neuroendocrine neoplasms (NENs);diagnosis;Chemotherapy;Immunotherapy21|0|0Updated：2025-12-13 -
Bone-organ axes: bidirectional crosstalk AI Introduction
“Reporting on the latest research, this review delves into the bidirectional communication between bone and various organs, with a spotlight on osteokines and the role of extracellular vesicles in bone-organ interactions. It lays a foundation for developing physiologically relevant in vitro models and offers insights into bone-organ axis-related diseases.”
Abstract：In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines (also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles (EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.Keywords：Bone-organ axes;Bidirectional crosstalk;cytokines;Osteokines;Extracellular vesicles (EVs);Hormones;Metabolites40|1|0Updated：2025-12-13
REVIEW
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Alleviating mitochondrial dysfunction in diabetic cardiomyopathy through the Adipsin and Irak2 pathways AI Introduction
“In the field of xxx, expert xx has made significant research progress. They established the xx system/explored the xx topic/verified the xx conjecture, offering solutions to tackle xx problems and paving the way for future research in xx.”Keywords：Diabetic cardiomyopathy;Mitochondrial function;Lipotoxicity;Cardiomyocytes;Interleukin-1 receptor-associated kinase-like 2 (Irak2);interleukin-1;Protein kinase R24|0|0Updated：2025-12-13 -
In situ genetic engineering of host T-cells based on acellular scaffold strategy: a big but also small step for solid tumor immunotherapy AI Introduction“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Acellular biomaterial scaffold;T-cell therapy;Solid tumor immunotherapy;Biomaterial-biosystem interaction;Multidisciplinary and interdisciplinary;Clinical transformation23|0|0Updated：2025-12-13 -
Emerging roles of ADP-dependent glucokinase in prostate cancer AI Introduction
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, they have provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Prostate cancer (PCa);ADP-dependent glucokinase (ADPGK);Aldolase C;AMP-activated protein kinase (AMPK);Glycolysis27|0|0Updated：2025-12-13
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