APMIS

Wang, Lei; Wu, Guangyao; Li, Xixia; Liu, Xiaoqin; Xu, Xiaoyan

doi: 10.1111/apm.70045pmid: 40678918

Chronic rhinosinusitis with nasal polyps (CRSwNP) lacks effective therapies, highlighting miRNAs as potential therapeutic targets owing to their biological functions and analytical accessibility. This study aimed to investigate the role of miR‐145‐5p in CRSwNP. Serum samples and inferior turbinate mucosa tissues were collected from 175 CRSwNP patients and 90 nasal septum deviation (NSD) subjects. qRT‐PCR measured miR‐145‐5p expression in serum and tissue samples, and CD40 expression in tissues. ROC curve evaluated the diagnostic efficacy. Associations with disease severity and eosinophilic CRSwNP (ECRSwNP) risk were analyzed through correlation and logistic regression analysis. Dual‐luciferase assay confirmed miR‐145‐5p targeting CD40. LPS‐induced inflammation in human nasal epithelial cells (hNEpCs) assessed the miR‐145‐5p/CD40 axis's impact on IL‐6, IL‐1β, and TNF‐α levels. Tissue and serum miR‐145‐5p effectively diagnosed CRSwNP. Reduced miR‐145‐5p correlated with disease severity and was an independent ECRSwNP risk factor. In LPS‐stimulated hNEpCs, miR‐145‐5p overexpression suppressed IL‐6, IL‐1β, and TNF‐α. CD40 expression inversely correlated with miR‐145‐5p and amplified inflammatory responses mitigated by miR‐145‐5p overexpression. MiR‐145‐5p, serving as a diagnostic biomarker for CRSwNP, was negatively correlated with disease severity. MiR‐145‐5p overexpression attenuated inflammation in hNEpCs by targeting CD40, thereby involving itself in the progression of CRSwNP, suggesting therapeutic potential for CRSwNP management.

doi: 10.1111/apm.13434pmid: N/A

Fang, Jian; Liao, Liang

doi: 10.1111/apm.70042pmid: 40653697

Abnormal white blood cell (WBC) counts have been associated with ventilator‐associated pneumonia (VAP). However, the prognostic value of WBC trajectory changes in VAP patients remains understudied. This study aimed to explore the correlation between WBC trajectory changes and the 30‐day mortality rate in VAP patients. Data from VAP patients in the MIMIC‐IV database were included. Group‐based trajectory analysis was used to categorize patients based on their WBC patterns within 7 days of ICU admission. Cox proportional hazards regression analysis was conducted to assess the association between WBC trajectories and 30‐day mortality. A total of 1194 eligible VAP patients were included. Five distinct WBC trajectories were identified. Compared to the trajectory group with continuously normal WBC levels (Class 5), the group with initially high levels but subsequent decrease (Class 2) and the group with continuously increasing WBC levels (Class 3) showed independent associations with increased mortality (OR > 1, p < 0.05). Additionally, restricted cubic splines (RCS) results indicated a possible linear relationship between WBC counts on the 6th and 7th days and the 30‐day survival status of VAP patients. Within the first week of ICU admission, both the group with initially low levels but persistently increasing WBC trajectories and the group with initially high levels but continuously decreasing WBC trajectories were associated with increased 30‐day mortality in VAP patients. This finding offers insights into predicting short‐term mortality risks related to VAP and aids clinicians in early identification of high‐risk patients.

Gopalakrishnan, Vinoj; Saravanan, Vaijayanthi; Mahendran, Maria Infant Majula Shifani; Boopathy, Vinoth; Vaithianathan, Rajan; Srinivasan, Sowmya; Krishnamurthy, Srikrishna

doi: 10.1111/apm.70041pmid: 40590168

Colorectal cancer (CRC) is a rising threat in modern populations, driven by reduced dietary fiber intake, pollution, poor hygiene, and especially the overuse of antibiotics. Anaerobe‐induced CRC has emerged as a focal area in current research, with particular attention to anaerobic pathogenic bacteria such as Helicobacter pylori, Fusobacterium nucleatum, Solobacterium moorei, Bacteroides fragilis toxin (BFT), Peptostreptococcus anaerobius, and Parvimonas micra. Pathogens inhabit concerning niche within the gut, releasing virulence factors that disrupt gut microbiota homeostasis, leading to significant dysbiosis and chronic inflammation. Persistent inflammatory state activates various inflammatory markers, triggering cancer‐associated signaling pathways. Moreover, bacterial toxins and biofilm formation exacerbate these effects by activating multiple malignant signaling pathways. Review explores recent advances in therapeutic strategies, emphasizing the importance of a deeper understanding of anaerobes and their pivotal roles in CRC progression. We highlight the major anaerobes likely to be classified as grade I carcinogens in the future and underscore the critical need for effective interventions to mitigate their impact on CRC development.

Goshisht, Manoj Kumar

doi: 10.1111/apm.70050pmid: 40667603

The rampant increase in antimicrobial resistance and stagnant pipeline of antibiotic development is a global concern. Biofilms further make the infections more persistent and incurable by providing a protective environment to the microbes. It demands the development of innovative therapeutics without delay. Nanomaterial‐based therapeutics is a promising approach to combat deadly bacterial infections. The distinct shape, size, and physical characteristics of nanomaterials (NMs) make them able to target biofilms through various mechanisms and thrash recalcitrant deadly infections. This comprehensive review describes (i) historical perspective of antibiotics and their role in combating microbes; (ii) different mechanisms through which bacteria develop resistance against antibiotics; (iii) different sensing mechanisms to detect bacteria; (iv) NMs to treat planktonic bacteria; (v) NMs to treat biofilms (both oral and wound biofilms); (vi) different types of NMs (e.g., metal NMs, polymeric NMs, carbon NMs) along with photothermal effects to combat microbes.

Zhang, Tao; Xiao, Jing; Chen, Wenzhao

doi: 10.1111/apm.70043pmid: 40611699

The aim of this study is to explore the correlation between the levels of miR‐222‐3p and the onset of acute pancreatitis (AP) and further verify the role of miR‐222‐3p in the pathogenesis of AP through targeted regulation of Sirtuin 1 (SIRT1). This study encompassed a total of 160 AP patients, including 80 patients with mild and moderate AP (non‐SAP) and 80 patients with severe AP (SAP). The levels of miR‐222‐3p and SIRT1 were detected by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) technology, and the potential significance of miR‐222‐3p in the diagnosis of AP was evaluated by receiver operating characteristic curve. The proliferation activity of cerulein‐induced HPDE6‐C7 cells was investigated by Cell Counting Kit‐8 method. Meanwhile, the changes in the levels of inflammatory factors were quantified using enzyme‐linked immunosorbent assay (ELISA) kits. The result showed that miR‐222‐3p was elevated in AP patients, especially in SAP patients. Elevated miR‐222‐3p levels showed diagnostic significance for AP. Inhibiting miR‐222‐3p promoted the proliferation of cerulein‐damaged HPDE6‐C7 cells and reduced inflammatory factor increases induced by cerulein. SIRT1 inhibition reversed the effects of miR‐222‐3p on cerulein‐induced HPDE6‐C7 cells. Inhibition of miR‐222‐3p may alleviate the development of AP by targeting SIRT1.

Kapoor, Utsav; Aboujaoude, Michael T.; Cios, Konrad J.; Chobrutskiy, Andrea; Chobrutskiy, Boris I.; Blanck, George

doi: 10.1111/apm.70053pmid: 40653843

While the role of anti‐cytomegalovirus (CMV) T‐cell responses in the cancer setting is becoming increasingly recognized, the association between CMV and survival outcomes has not been subject to study through more recent immunogenomic approaches. Thus for this study, we extracted T‐cell receptor (TCR) recombination reads from whole exome sequencing (WXS) and RNA sequencing (RNAseq) files of stomach adenocarcinoma (STAD) and soft tissue sarcoma (SARC) samples from the Cancer Genome Atlas (TCGA) and matched the corresponding TCR complementarity determining region‐3 (CDR3) amino acid (AA) sequences represented by these reads to known anti‐CMV CDR3 sequences. Results indicated that the recovery of both TRA and TRB recombination reads from WXS files, from either blood or tumor samples, which corresponded to AA sequences matching anti‐CMV CDR3s, correlated with better survival probabilities for both STAD and SARC. However, TCR CDR3s represented by recombination reads recovered from RNAseq files and matching anti‐CMV TCR CDR3 AA sequences correlated with lower survival probabilities. These results raise the question of whether exposure to CMV prior to onset or progression of cancer may lead to better survival probability whereas a potentially active T‐cell response to CMV during cancer onset or progression could represent an ongoing comorbidity? In conclusion, TCR CDR3s may be an important indicator of prognosis for stomach cancer and soft tissue sarcoma and may support further research into anti‐CMV CDR3s as a tool for development of immunotherapy for these cancers.

Wiik, Erik Nesje; Pettersen, Henrik Sahlin; Skogseth, Haakon; Halgunset, Jostein; Wibe, Arne

doi: 10.1111/apm.70051pmid: 40642870

miR‐143 and miR‐145 have been reported as downregulated in colorectal cancer (CRC) compared to normal mucosa, with regulatory effects on proteins involved in carcinogenesis. These findings primarily derive from tissue homogenate analyses and experimental models. The present study employs in situ methodology to reassess miR‐143 and miR‐145 expression in CRC and their associations with validated protein targets within the native tumor microenvironment. Expression patterns of miR‐143, miR‐145, and eight previously experimentally validated target proteins were analyzed in clinical samples from 100 CRC patients using in situ hybridization, immunohistochemistry, and deep learning‐based epithelial segmentation. Expression levels of miR‐143 and miR‐145 showed no significant difference between CRC and normal mucosa, though considerable inter‐patient variability was observed. Among 11 examined miRNA‐protein relationships, only four showed significant correlations, exhibiting positive associations that contrast with previously reported inverse relationships. Subgroup analyses revealed no statistically significant association between miRNA expression variability and examined clinicopathological parameters. These findings highlight the importance of in situ validation for results obtained from tissue homogenates and in vitro experiments. Additional research is warranted to determine the prognostic significance of miR‐143 and miR‐145 in clinical outcomes.