In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction.

Calcification is a clinical marker of atherosclerosis. This review focuses on recent findings on the association between calcification and plaque vulnerability. Calcified plaques have traditionally been regarded as stable atheromas, those causing stenosis may be more stable than non-calcified plaques. With the advances in intravascular imaging technology, the detection of the calcification and its surrounding plaque components have evolved. Microcalcifications and spotty calcifications represent an active stage of vascular calcification correlated with inflammation, whereas the degree of plaque calcification is strongly inversely related to macrophage infiltration. Asymptomatic patients have a higher content of plaque calcification than that in symptomatic patients. The effect of calcification might be biphasic. Plaque rupture has been shown to correlate positively with the number of spotty calcifications, and inversely with the number of large calcifications. There may be certain stages of calcium deposition that may be more atherogenic. Moreover, superficial calcifications are independently associated with plaque rupture and intraplaque hemorrhage, which may be due to the concentrated and asymmetrical distribution of biological stress in plaques. Conclusively, calcification of differential amounts, sizes, shapes, and positions may play differential roles in plaque homeostasis. The surrounding environments around the calcification within plaques also have impacts on plaque homeostasis. The interactive effects of these important factors of calcifications and plaques still await further study.

No abstract

Shi XZ, Winston JH, Sarna SK. Differential immune and genetic responses in rat models of Crohn's colitis and ulcerative colitis.

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords “NLRP3” and “extracellular vesicles” appeared most frequently. Besides, researches on COVID-19–induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19–induced ALI and may be a target for the treatment of COVID-19.

PurposeTo examine the expression of pro-interleukin-1β (pro-IL-1β) and interleukin-1β (IL-1β) in the vitreous body of patients with neovascular age-related macular degeneration(nAMD), polypoidal choroidal vasculopathy (PCV), proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or Eales’ disease to further elucidate the role of IL-1β and inflammation in the pathogenesis of neovascular retinal disease.DesignProspective clinical laboratory investigation study.MethodsAll patients enrolled had vitreous hemorrhage due to nAMD, PCV, PDR, RVO or Eales’ disease that required vitrectomy. Patients were excluded for any history of active intraocular inflammation, or other ophthalmic surgery besides vitrectomy. Control samples were obtained from patients with idiopathic macular epiretinal membrane. A total of fifty vitreous samples were collected from patient during vitrectomy. Pro-IL-1β and IL-1β expression were measured by enzyme-linked immunosorbent assay (ELISA). Results were analyzed statistically using nonparametric tests.ResultsExpression of pro-IL-1β protein was increased by 2.83-fold and 9.19-fold in PCV and nAMD vitreous samples relative to control, respectively. Expression of IL-β protein was increased by 10-fold and 4.83-fold in PCV and nAMD vitreous samples relative to control, respectively.ConclusionsOur results demonstrate that expression of pro-IL-1β and IL-1β proteins is higher in PCV and nAMD. The roles of pro-IL-1β and IL-1β as inflammatory mediators in the development of PCV and nAMD may be associated with photoreceptor degeneration and neovascularization which necessitates further study.

We reported previously that mechanical stretch in rat colonic obstruction induces cyclooxygenase (COX)-2 expression in smooth muscle cells. The aims of the present study were to investigate whether in vivo treatment with COX-2 inhibitor has prophylactic and therapeutic effects on motility dysfunction in colon obstruction, and if so what are the underlying mechanisms. Partial colon obstruction was induced with a silicon band in the distal colon of 6 -8-wk-old Sprague-Dawley rats; obstruction was maintained for 3 days or 7 days. Daily administration of COX-2 inhibitor NS-398 (5 mg/kg) or vehicle was started before or after the induction of obstruction to study its prophylactic and therapeutic effects, respectively. The smooth muscle contractility was significantly suppressed, and colonic transit rate was slower in colonic obstruction. Prophylactic treatment with NS-398 significantly prevented the impairments of colonic transit and smooth muscle contractility and attenuated fecal collection in the occluded colons. When NS-398 was administered therapeutically 3 days after the initiation of obstruction, the muscle contractility and colonic transit still improved on day 7. Obstruction led to marked increase of COX-2 expression and prostaglandin E 2 (PGE2) synthesis. Exogenous PGE2 decreased colonic smooth muscle contractility. All four PGE2 E-prostanoid receptor types (EP1 to EP4) were detected in rat colonic muscularis externa. Treatments with EP1 and EP3 antagonists suppressed muscle contractility in control tissue but did not improve contractility in obstruction tissue. On the contrary, the EP2 and EP4 antagonists did not affect control tissue but significantly restored muscle contractility in obstruction. We concluded that our study shows that COX-2 inhibitor has prophylactic and therapeutic benefits for motility dysfunction in bowel obstruction. PGE2 and its receptors EP2 and EP4 are involved in the motility dysfunction in obstruction, whereas EP1 and EP3 mediate PGE2 regulation of colonic smooth muscle contractile function in normal state.

Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. However, it is unknown whether BMSCs-derived exosomes exert their therapeutic effect against sepsis-induced lung injury by inhibiting glycolysis in macrophages. Therefore, the present study aimed to evaluate the anti-inflammatory effects of exosomes released from BMSCs on acute lung injury induced by lipopolysaccharide (LPS) in mice and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs inhibited M1 polarization and promoted M2 polarization in MH-S cells (a murine alveolar macrophage cell line) by releasing exosomes. Further experiments showed that exosomes secreted by BMSCs modulated LPS-treated MH-S cells polarization by inhibiting cellular glycolysis. Moreover, our results showed that BMSCs-derived exosomes down-regulated the expression of several essential proteins of glycolysis via inhibition of hypoxia-inducible factor 1 (HIF-1)α. Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.