PRISMA flow diagram.

<p>Flow diagram demonstrating the process of article selection for systematic review and meta-analysis.</p

Forest plots of the mortality rates from CVE.

<p>(A) Mortality from stroke. (B) Mortality from cardiac disease. (C) Mortality from overall CVE.</p

Forest plots of the incidence of CVE.

<p>(A) Incidence of stroke. (B) Incidence of cardiac disease. (C) Incidence of overall CVE. Data were calculated by a random-effects model. The boxes represent standardized mean differences (SMDs), and lines depict 95% CIs. The vertical solid line represents no difference between CPAP and control. Values to the right of the solid line favor CPAP benefit. Pooled SMDs and 95% CIs are represented by the diamond shapes.</p

A bilayer composite composed of TiO₂-incorporated electrospun chitosan membrane and human extracellular matrix sheet as a wound dressing

<div><p>We designed bilayer composites composed of an upper layer of titanium dioxide (TiO₂)-incorporated chitosan membrane and a sub-layer of human adipose-derived extracellular matrix (ECM) sheet as a wound dressing for full-thickness wound healing. The dense and fibrous top layer, which aims to protect the wound from bacterial infection, was prepared by electrospinning of chitosan solution followed by immersion in TiO₂ solution. The sponge-like sub-layer, which aims to promote new tissue regeneration, was prepared with acellular ECM derived from human adipose tissue. Using a modified drop plate method, there was a 33.9 and 69.6% reduction in viable <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> on the bilayer composite, respectively. In an <i>in vivo</i> experiment using rats, the bilayer composites exhibited good biocompatibility and provided proper physicochemical and compositional cues at the wound site. Changes in wound size and histological examination of full-thickness wounds showed that the bilayer composites induced faster regeneration of granulation tissue and epidermis with less scar formation, than control wounds. Overall results suggest that the TiO₂-incorporated chitosan/ECM bilayer composite can be a suitable candidate as a wound dressing, with an excellent inhibition of bacterial penetration and wound healing acceleration effects.</p></div

The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury

<div><p>Introduction</p><p>Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis.</p><p>Methods</p><p>The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used.</p><p>Results</p><p>Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-β. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-β levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-β than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis.</p><p>Conclusion</p><p>Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.</p></div

Adoptive transfer of M1 or M2c macrophages following liposome clodronate (LC) treatment.

<p>(A) As seen by Masson’s trichrome staining, transferring M2c cells following the LC treatment led to the complete reversion of the improvement of interstitial fibrosis, a. IRI+PBS (IRI), b. liposome clodronate (IRI+LC), c. M2 (IRI+LC+M2c) Magnification: ×100, (n = 4–5 per group), (B) As seen by Masson’s trichrome staining, transferring M1 macrophages into LC-treated mice did not affect the degree of fibrosis, a. IRI+PBS (IRI), b. liposome clodronate (IRI+LC), c. M1 (IRI+LC+M1) Magnification: ×100, (n = 4–5 per group), *p < 0.05 compared to sham, **p < 0.05 compared to IRI, ^#p < 0.05 compared to LC.</p

Diphtheria toxin injection in CD11c DTR transgenic mice.

<p>(A) An RT-PCR analysis showed no significant difference in the level of mRNA expression of arginase and iNOS in the kidneys. (n = 4–5 per group), (B) Diphtheria toxin injection resulted in no significant change in renal fibrosis on day 28, as seen by Masson’s trichrome staining and (C) in TGF-β mRNA expression throughout the recovery phase. Magnification: ×100. (n = 4–5 per group), *p < 0.05 compared to WT+DT, ^†p < 0.05 compared to the previous time point.</p

Renal histology following a unilateral ischemia reperfusion injury.

<p>(A) As seen by periodic acid-Schiff (PAS) staining, the tubular injury was partially restored from day 3 to day 28 (D3 to D28). (B) As seen by Masson’s trichrome (MT) staining, we observed the development and progression of interstitial fibrosis in the kidneys during the 28 days. (n = 5–6 per group), (C) In immunohistochemical staining, we detected the upregulation of TGF-β. Magnification: ×100, (n = 4–6 per group), *p < 0.05 compared to day 0, ^†p < 0.05 compared to the previous time point.</p

Diphtheria toxin injection into CD11b DTR transgenic mice.

<p>(A) An RT-PCR analysis showed the relative reduction in the mRNA expression level of arginase-1. However, on day 7, it was less significant than the reduction observed in kidney of liposome clodronate-treated mice. (n = 4–5 per group), (B) Diphtheria toxin injection resulted in no significant change in renal fibrosis on day 28, as seen by Masson’s trichrome staining, and (C) in TGF-β mRNA expression throughout the recovery phase. Magnification: ×100. (n = 4–5 per group), *p < 0.05 compared to WT+DT, ^†p < 0.05 compared to the previous time point.</p

The impact of macrophage depletion on kidneys during the recovery phase.

<p>(A) Treatment with LC during the recovery phase improved renal fibrosis (magnification, ×100) and it was associated with a significant reduction in (B) the expression of type IV collagen in kidneys and (C) the level of the pro-inflammatory cytokine IL-6, (n = 3–5 per group), (D) As seen by immunohistochemical staining, the TGF-β expression decreased significantly in the kidneys of clodronate-treated mice on day 28. The TGF-β mRNA expression in kidneys also significantly decreased following liposome clodronate injection during the recovery phase. Magnification: ×100, (n = 4–6 per group), *p<0.05 compared to sham, ^#p < 0.05 compared to IRI+PBS, ^†p < 0.05 compared to the previous time point.</p