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management of absorptive deficiencies.

Macrophages are key regulators of inflammation and cancer promotion in the liver, and their recruitment and activation is linked to chemokine receptor signaling. However, the exact roles of the chemokine receptors CCR2 and CCR5 for macrophage functions in the liver is obscure.

To study CCR2 and CCR5 in inflammatory liver injury, we used mice with a hepatocyte-specific knock-out of the nuclear factor κB (NF-κB) essential modulator (NEMO), termed NEMO

mice, and generated NEMO

Ccr2

and NEMO

Ccr5

mice. NEMO

mice develop hepatitis and fibrosis after two and liver tumors after six months.

We found that both CCR2 and CCR5 deficiency led to reduced fibrosis, while CCR5 deficiency increased steatosis and tumor burden in NEMO

mice. CCR2 was required for recruitment of hepatic macrophages, whereas CCR5 promoted stellate cell activation. The reduction of monocytes and macrophages by either anti-Gr1 antibody or clodronate-loaded liposomes (CLL), but not of CD8

T cells or NK cells, significantly aggravated liver injury in NEMO

mice and was further increased in NEMO

Ccr5

mice. CLL-induced liver injury was dampened by the adoptive transfer of exvivo generated macrophages, whereas the adoptive transfer of control CD115

immature monocytes or B cells did not reduce liver injury.

Although CCR2 and CCR5 principally promote liver fibrosis, they exert differential functions on hepatic macrophages during liver disease progression in NEMO

mice. While CCR2 controls the recruitment of monocytes to injured livers, CCR5-dependent functions of liver macrophages limit hepatic injury, thereby reducing steatosis and hepatocarcinogenesis.

Although CCR2 and CCR5 principally promote liver fibrosis, they exert differential functions on hepatic macrophages during liver disease progression in NEMOLPC-KO mice. While CCR2 controls the recruitment of monocytes to injured livers, CCR5-dependent functions of liver macrophages limit hepatic injury, thereby reducing steatosis and hepatocarcinogenesis.There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12α-hydroxylated BAs to non-12α-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4β-hydroxycholesterol (4βOH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4βOH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4βOH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12α-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.Lysozymes, which are secreted in many organisms, including invertebrates, mammals, plants, bacteria and fungus, exhibit antimicrobial, antiviral, antioxidant, and anti-inflammatory activities. Splys-i is an invertebrate-type (i-type) lysozyme isolated from Scylla paramamosain in 2017 and is involved in immune defense against bacteria. However, the antibacterial, antioxidant, and anti-inflammatory activities of Splys-i remain to be elucidated. In the current study, the expression parameters (including IPTG concentration, induction temperature, and induction duration) of Splys-i in Escherichia coli were optimized to achieve high-level yield through shake-flask cultivation with approximately 120 mg of Splys-i obtained from 1 L of LB medium. The purified Splys-i displayed low cytotoxicity to RAW264.7 macrophage cells and low hemolytic activity against erythrocytes of mouse, rat, and rabbit, respectively, and exhibited potent antibacterial activity against both Gram-positive and -negative bacteria with minimum concentrations ranging from 15 to 90 μg/mL. The antibacterial property of Splys-i was also unaffected when treated with various temperature, pHs, and salinity, respectively, and Splys-i showed resistance to proteinase digestion. Radical-scavenging rate assay (including ABTS+, DPPH, hydroyl free radical, and superoxide anion) indicated that Splys-i was an efficient antioxidant. Splys-i also exerted anti-inflammatory effect through the inhibition of IκBα and NF-κB(P65) phosphorylation, thereby reducing the secretion of pro-inflammatory cytokines. All these results suggested that Splys-i can be prepared from E. coli with potent biological property.Molybdenum trioxide (MoO3) nanoparticles (NPs) embedded in polymer films have been proposed as a cheap way of producing antibacterial coatings on external surfaces. Recently, we synthesized MoO3 nanowires in a unique shape and degree of anisotropy, which enables their fast water dissolution and quick antimicrobial reaction. Potential human health risks following the exposure to MoO3 NPs however need to be assessed prior their wide use. We therefore, investigated the biological effect of these newly synthesized MoO3 NPs on the human keratinocyte cell line HaCaT, used here as a model for the human skin. Exposure of HaCaT cells to 1 mg/mL MoO3 NPs concentration for 1 h showed no effect on cell survival, had no influence on reactive oxygen species production, expression of proteins involved in antioxidant defense, secretion of pro-inflammatory cytokines, nor induced DNA damage. Interestingly however, ERK and p38 MAP kinases were activated, and upon longer time exposure, induced a moderate release of the pro-inflammatory cytokine interleukin 6, increased DNA damage and increased the level of caspase independent cell death. Our study indicates that exposing HaCaT cells to antibacterial MoO3 NPs water-based solution in durations less than 1 h exhibits no cytotoxicity, but rather triggers cell signalling involved in cell survival and inflammation; which should be taken into consideration when evaluating MoO3 NPs for medical applications.

Clinically, surgical treatment and sclerotherapy are the main treatments for lymphatic malformation (LM), but the diagnosis and treatment of microcystic LM has numerous pitfalls. DMH1 TGF-beta inhibitor Microcystic LM within the vagina and pelvis is not easily visible, and there are many side effects of treatment. Lymphangiography, a relatively old method of identifying diseases of the lymphatic system, has been rarely used in clinical settings because of the difficulty of performing this test. In this article, we describe the use of a special lesion site adjacent to the nearby lymph nodes for the treatment of vaginal and pelvic microcystic LM.

Lymphangiography was performed using lymph node aspiration combined with direct local puncture of the lesion, guided by the injection of iodine oil, which can produce a better outcome and more complete removal of the lesion. Finally, sclerotherapy was conducted using a low concentration of 50% ethanol with good fluidity, which covered the lesion to a great extent. This methodology was shown to be effective in treating children with vaginal and pelvic microcystic LM.

Lymphangiography was performed using lymph node aspiration combined with direct local puncture of the lesion, guided by the injection of iodine oil, which can produce a better outcome and more complete removal of the lesion. Finally, sclerotherapy was conducted using a low concentration of 50% ethanol with good fluidity, which covered the lesion to a great extent. This methodology was shown to be effective in treating children with vaginal and pelvic microcystic LM.

The transpsoas lateral lumbar interbody fusion (LLIF) is a commonly used technique to manage various spinal conditions. LLIF is often performed in combination with posterior lumbar instrumentation, which requires patient repositioning or staging of the procedure. Here we present a step-by-step detailed description of a prone LLIF using an intraoperative laser level to guide orthogonal insertion of instrumentation.

A 57-year-old man with history of L4-S1 instrumentation, who developed symptomatic adjacent L3L/4 level stenosis and sagittal plane imbalance. The single position prone lateral lumbar interbody fusion with posterior fixation was chosen in order to minimize operative room time and optimize lumbar lordosis (LL) correction.

The patient was positioned prone on a Jackson table. link2 This position allowed for improved LL correction. A self-leveling laser line ensured ideal orthogonal use of instrumentation. The patient had improvement of symptoms immediately postoperatively and was discharged home on postoperative day 2 without complications.

The single position prone LLIF with posterior fixation offers a shorter operative room time by eliminating necessity to reposition the patient between stages of operation. The prone position of the patient optimizes LL correction. Further experience with this approach will allow for refining of the technique to overcome its limitations and facilitate its utilization.

The single position prone LLIF with posterior fixation offers a shorter operative room time by eliminating necessity to reposition the patient between stages of operation. The prone position of the patient optimizes LL correction. Further experience with this approach will allow for refining of the technique to overcome its limitations and facilitate its utilization.IQ motif containing GTPase-activating protein 3 (IQGAP3) has been implicated in diverse cellular processes, including neuronal morphogenesis, cell proliferation and motility, and epithelial-mesenchymal transition. However, its role in cancer radioresistance is completely unknown. link3 Here, we report that IQGAP3 is overproduced in lung cancer patients and correlates with poor clinical outcomes. Functionally, we demonstrate that depletion of IQGAP3 impairs oncogenesis and overcomes radioresistance in lung cancer in vitro and in vivo. Mechanistically, we uncover that IQGAP3 interacts with Rad17 and controls its expression to activate the ATM/Chk2 and ATR/Chk1 signaling pathways by recruiting the Mre11-Rad50-Nbs1 (MRN) complex in response to DNA damage. Moreover, Rad17 is identified as the major downstream effector that mediates the functions of IQGAP3 in lung cancer. Clinically, IQGAP3 overexpression positively correlates with Rad17 upregulation in human lung cancer tissues. Collectively, these data support key role for IQGAP3 in promoting lung cancer radioresistance by interacting with Rad17 and suggest that targeting IQGAP3 may be an attractive strategy for lung cancer radiotherapy.