Apmis

doi: 10.1111/apm.13241pmid: N/A

Pang, Jiangna; Wu, Yongfu; Ji, Yanlin; Si, Yilan; Liang, Fang

doi: 10.1111/apm.13321pmid: 37185991

The clinical application of human‐derived mesenchymal stem cells (hMSCs) in osteoporosis (OP) treatment is promising. We aimed to uncover the role of circular RNA 0006873 (circ_0006873) in OP progression using hMSCs. The levels of circ_0006873, pantothenate kinase 2 (PANK2) messenger RNA (mRNA), microRNA‐20a (miR‐20a), SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) mRNA and the mRNA levels of osteogenesis‐related markers were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). The protein expression of osteogenesis‐related markers and SMURF2 was detected by Western blot assay. Alkaline phosphatase (ALP) staining and activity were determined using an ALP staining Kit and an ALP Colorimetric Assay Kit. Circ_0006873 was highly expressed in the serum samples and bone tissue samples of OP patients compared with control cases. Circ_0006873 overexpression down‐regulated the expression of osteogenesis‐related markers and reduced ALP staining and activity. Circ_0006873 down‐regulated miR‐20a level through its interaction with miR‐20a in hMSCs. Circ_0006873 suppressed osteogenic differentiation through targeting miR‐20a. SMURF2 was a molecular target of miR‐20a, and miR‐20a promoted osteogenic differentiation through targeting SMURF2. Circ_0006873 suppressed the osteogenic differentiation of hMSCs by upregulating SMURF2 level via sponging miR‐20a in vitro.

Jensen, Louise Kruse; Birch, Julie Melsted; Jensen, Henrik Elvang; Kirketerp‐Møller, Klaus; Gottlieb, Hans

doi: 10.1111/apm.13312pmid: 36951581

Two chronic osteomyelitis patients, a diabetic foot osteomyelitis patient and a fracture‐related infection patient, all with staphylococci‐positive microbiology, were examined to confirm the clinical relevance of bacterial invasion of the submicron osteocyte lacuna–canaliculi network (OLCN) in bone tissue. Based on immunohistochemistry and light microscopy both Staphylococcus aureus and Staphylococcus epidermidis were identified within the OLCN of all four patients. The findings consolidate that bacterial OLCN invasion is a clinically relevant part of osteomyelitis disease biology, which from experimental porcine infections, seems to be time depending. The microscopy pictures of the four patients significantly add to visualize the phenomenon of bacterial OLCN invasion.

Jääskeläinen, Anu E.; Salmenlinna, Saara; Antikainen, Jenni; Sihvonen, Reetta; Ahava, Maarit; Tarkka, Eveliina; Pätäri‐Sampo, Anu

doi: 10.1111/apm.13319pmid: 37186317

Shiga toxin (stx)‐producing Escherichia coli (STEC) causes potentially severe gastrointestinal infections. Due to its public health importance, control measures are required, and carriers may need to refrain from work or daycare when the risk of spread to vulnerable people is high. We evaluated the use of direct stool multiplex PCR compared to culture for primary STEC diagnostics and for follow‐up in order to update the national guidelines for STEC monitoring. We analyzed primary and follow‐up samples of 236 STEC PCR‐positive cases at HUSLAB, Helsinki, Finland in 2016–2017, altogether 858 samples. All STEC PCR‐positive samples were inoculated on non‐selective chromogenic agar plates. Culture positivity was confirmed from culture sweeps by PCR. 211 (89%) of the cases were culture positive in their primary sample. Of all primary and follow‐up samples, 499 were PCR positive and of these 450 (90%) were culture positive. PCR‐negative follow‐up samples were available from 125 cases. Of these, 88 cases were followed for at least three consecutive PCR‐negative samples. Two cases (2%) had culture‐positive sample(s) after two consecutive PCR‐negative samples. The median time for STEC clearance was 22–23 days. The laboratory‐developed multiplex PCR test used in this study is a reliable method for STEC diagnostics and follow‐up in a clinical laboratory. When non‐selective methodology is used, the majority of PCR‐positive samples (90%) are also culture positive. Furthermore, only two cases (2%) in our material had two consecutive PCR‐negative samples followed by positive samples. Consequently, to demonstrate the clearance from STEC infection, we consider two PCR‐negative follow‐up samples sufficient. The Finnish national guidelines for STEC monitoring have been updated accordingly.

Davari, Fatemeh; Shokri‐Shirvani, Javad; Sepidarkish, Mahdi; Nouri, Hamid Reza

doi: 10.1111/apm.13323pmid: 37170445

Helicobacter Pylori (H. Pylori) cause peptic ulcer disease (PUD), but the inflammasome's role in PUD is not well understood. Therefore this study has investigated inflammasome compartment expression and IL‐1β production in gastritis (G) and peptic ulcer disease. This study was based on gene expression of inflammasome compartments on stomach biopsies of 50 patients with PUD as cases and 50 individuals with gastritis as controls. The expression of NLRC4, ASC, IL‐18, and serum IL‐1β decreased in the PUD group compared to the control group. AIM2 gene expression increased, and NLRP12 gene expression decreased in H. pylori‐seropositive positive (HP+) individuals compared to H. pylori‐seronegative (HP−) individuals. The G‐HP+ subjects had higher serum IL‐1β and AIM2 gene expression than G‐HP− subjects but lower NLRP3 and NLRP12 gene expression. The PUD‐HP+ had lower serum IL‐1β, but higher AIM2 and IL‐18 expression than PUD‐HP−. The PUD‐HP− patients had decreased IL‐18 expression than G‐HP− group. The PUD‐HP+ had lower serum IL‐1β and NLRC4 expression than G‐HP+, while NLRP1 and NLRP3 were higher in expression in PUD‐HP+. The expression of caspase‐1, NLRP3 and NAIP were correlated with IL‐1β and IL‐18. In conclusion, a decrease in NLRC4, IL‐18, ASC genes, and IL‐1β levels in PUD patients compared to gastritis may act in the development of PUD. H. pylori caused AIM2 induction and reduced NLRP12, indicating their contribution to bacterial responses. Decreased NLRC4 expression and IL‐1β protein, together with enhanced NLRP1, and NLRP3 expression, promotes H. pylori to develop peptic ulcers.

Sha, Haoran; He, Xiaoyi; Yan, Kai; Li, Jiakang; Li, Xu; Xie, Yinyin; Yang, Yousheng; Deng, Yajuan; Li, Guoying; Yang, Junhua

doi: 10.1111/apm.13326pmid: 37145345

Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self‐reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive‐like behaviors and mood‐related indicators, and inflammation, verified by the increased levels of the pro‐inflammatory cytokine, in coprophagy‐blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease‐like phenotypes in the coprophagy‐blocked group were worse than those in the coprophagy‐unblocked group, including severer depressive symptoms and higher levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α and IFN‐γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.

Wardzyńska, Aleksandra; Pawełczyk, Małgorzata; Rywaniak, Joanna; Makowska, Joanna S.; Kowalski, Marek L.; Chałubiński, Maciej

doi: 10.1111/apm.13328pmid: 37139548

microRNAs are short, noncoding RNA molecules involved in many inflammatory processes including bronchial asthma. Rhinoviruses are the main cause of acute asthma attack and may be involved in miRNA profile dysregulation. The aim of the study was to investigate the serum miRNA profile during asthma exacerbation in middle‐aged and elderly patients. We also evaluated in this group in vitro response to rhinovirus 1b exposure. Seventeen middle‐aged and elderly asthmatics were admitted to an outpatient clinic during asthma exacerbation and within a period of 6–8 weeks later. Blood samples were collected from the subjects and PBMCs were isolated. Cells were cultured in the presence of Rhinovirus 1b and with the medium only, and, after 48 h. miRNA expression (miRNA‐19b, ‐106a, 126a, and ‐146a) isolated from serum and PBMCs (cultures) was evaluated with RT‐PCR. Cytokines (INF‐γ, TNF‐α, IL6, and Il‐10) in culture supernatants were evaluated with flow cytometry. On exacerbation visit patients demonstrated higher expression of serum miRNA‐126a and ‐146a as compared to follow‐up visit. There was a positive correlation between asthma control test results and miRNA‐19, ‐126a, ‐146a. There was no other significant association between patient characteristics and the miRNA profile. Rhinovirus exposure did not changed miRNA expression in PBMCs as compared to medium on both visits. Cytokine production in culture supernatants significantly increased after rhinovirus infection. The group of middle‐aged and elderly patients demonstrated changed levels serum miRNA during asthma exacerbation as compared to follow‐up visit; however, correlations between their expression and clinical features were hardly noticeable. Rhinovirus did not affect expression of miRNA in PBMCs; yet, it induced cytokine production.