Soft tissue infection and osteomyelitis caused by Mycobacterium farcinogenes after heart surgery: Case report and literature review of human cases.

Mycobacterium farcinogenes (M. farcinogenes) is rapidly growing mycobacterium, belonging to non-tuberculous mycobacterial (NTM). M. farcinogenes is an exceedingly rare causative agent of human infection. Only seven cases with M. farcinogenes infections in humans were reported. This is a case of soft tissue infection and osteomyelitis caused by M. farcinogenes after heart surgery. Microbial identification was achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The clinical outcome was favorable after surgical debridement and 4-month antibiotics treatment. We also provide a comprehensive literature review on this disease.

Role of NF-κB signaling pathway in hexavalent chromium-induced hepatotoxicity.

Hexavalent chromium Cr (VI) is a primary human carcinogen with damaging toxic effects on multiple organs. Cr (VI) exposure can induce hepatotoxicity through oxidative stress, but its exact mechanism of action was still unclear. In our study, a model of acute Cr (VI) induced liver injury was established by exposing mice to different concentrations (0, 40, 80, and 160 mg/kg) of Cr (VI); RNA-seq was used to characterize changes in liver tissue transcriptome of C57BL/6 mice after exposing to 160 mg/kg Bw of Cr (VI). Changes in liver tissue structures, proteins, and genes were observed by hematoxylin and eosin (H&E), western blot, immunohistochemistry and RT-PCR. After Cr (VI) exposure, abnormal liver tissue structure, hepatocyte injury, and hepatic inflammatory response were observed in mice in a dose-dependent manner. RNA-seq transcriptome results indicated that oxidative stress, apoptosis, and inflammatory response pathways were increased after Cr (VI) exposure; KEGG pathway analysis found that activation of NF-κB signaling pathway was significantly upregulated. Consistent with the RNA-seq results, immunohistochemistry showed that Cr (VI) exposure resulted in infiltrating of Kupffer cells and neutrophils, increasing expression of inflammatory factors (TNF-α, IL-6, IL-1ß), and activating of NF-κB signaling pathways (p-IKKα/ß and p-p65). However, ROS inhibitor, N-acetyl-L-cysteine (NAC), could reduce infiltration of Kupffer cells and neutrophils and expression of inflammatory factors. Besides, NAC could inhibit NF-κB signaling pathway activation, and alleviate Cr (VI)-induced liver tissue damage. Our findings strongly suggested that inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)-associated liver fibrosis. Our findings revealed for the first time that Cr (VI) induced liver tissue damage through the inflammatory response mediated by the NF-κB signaling pathway, and inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)-associated hepatotoxicity.

N-acetyl-L-cysteine attenuated the toxicity of ZIF-8 on EA.hy926 endothelial cells by wnt/ß-catenin pathway.

As kinds of porous crystalline compounds, zeolitic imidazolate frameworks (ZIFs) have been developed quickly and attracted considerable attention for use in nano drug delivery systems, which raised concerns about cardiovascular disorders. At the present, the cytotoxic mechanism of ZIFs in cardiovascular disorders was still unclear. Our experiment explored the toxicity of ZIF-8, a typical kind of ZIFs, on human EA.hy926 vascular endothelial cells. The cell viability, ROS formation, apoptosis level, inflammatory response level, wound healing ability and atherosclerosis-related indicators of EA.hy926 endothelial cells were analyzed after ZIF-8 treatment. Meanwhile, we evaluated the ability of antioxidant N-Acetyl-L-cysteine (NAC) to attenuate the toxicity of ZIF-8 on EA.hy926 endothelial cells. As results, NAC attenuated ROS formation, cell apoptosis, LDH formation and endothelial dysfunction caused by ZIF-8. As the Wnt/ß-catenin pathway was involved in endothelial cell dysfunction, we also studied the expression level of ß-catenin and LEF1 in ZIF-8 and/or NAC treated EA.hy926 cells. As expected, ZIF-8 increased the protein expressions of ß-catenin and LEF1in the IC50 group, which was significantly inhibited by co-treatment with NAC. Taken together, this study could help improve our understanding about the mechanism of ZIF-8-induced endothelial cells injury and NAC had therapeutic potential in preventing ZIF-8-associated endothelial dysfunction by wnt/ß-catenin pathway.

A Continuum Robotic Cannula With Tip Following Capability and Distal Dexterity for Intracerebral Hemorrhage Evacuation.

OBJECTIVE: This paper aims to investigate a new continuum robot design and its motion implementation methods appropriate for a minimally invasive intracerebral hemorrhage (ICH) evacuation. METHODS: We propose a continuum robotic cannula, consisting of a precurved body and a 2-degree-of-freedom (DoF) flexible tip, monolithically fabricated. Kinematic model with cable elongation model, and a dedicated design optimization and motion planning algorithm were developed to enable the follow-the-leader (FTL) motion of the cannula. A task-dependent Jacobian-based closed loop control was also designed to track the cannula motion during the insertion and its independent tip motion. RESULTS: Comprehensive experiments were conducted to verify the kinematic model and submillimeter motion coupling between the cannula precurved body and its flexible tip. The cannula was also capable of achieving FTL motion within around 2.5 mm shape deviation and control performance within submillimeter errors. It was finally demonstrated to be capable of the nonlinear insertion and tip manipulation in the brain phantom. CONCLUSION: The new cannula design, together with the proposed algorithms, provides the unique ability to access ICH in a nonlinear trajectory and dexterous tip motion. SIGNIFICANCE: These motion capabilities of the robot in such a slender form factor will lead to more complete ICH evacuation and reduced trauma to the healthy brain tissues.

Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal-regulating kinase 1/c-Jun amino-terminal kinase signaling.

With the spread of hexavalent chromium (Cr(VI)) contamination, Cr(VI)-induced hepatotoxicity has attracted increasing attention in recent years. To date, however, the exact mechanism of Cr(VI) toxicity remains unclear. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK1)/c-Jun amino-terminal kinase (JNK) in Cr(VI)-induced hepatic toxicity and the possible related mechanisms. AML-12 hepatocyte cell-lines were treated with 0, 1, 4, and 16 µmol/Lof Cr(VI) with or without GS-444271 (an ASK1 inhibitor). Adult male mice were administered with 0, 2, 8, and 32 mg/kg body mass (BM)/day of Cr(VI) for 5 days. The level of hepatocyte apoptosis/proliferation, generation of reactive oxygen species (ROS), and expression levels of mRNAs and proteins related to ASK1/JNK and nuclear factor-E2-related factor 2 (Nrf2) signaling were assessed. Results showed that high Cr(VI) exposure induced hepatocyte apoptosis and liver injury by generation of ROS and down-regulation of Nrf2 signaling. In addition, ASK1/JNK signaling activity was upregulated in the Cr(VI)-treated group. Furthermore, GS-444217 treatment significantly rescued Cr(VI)-induced hepatocyte apoptosis and liver dysfunction in vitro and in vivo by down-regulation of ASK1/JNK signaling. Thus, ASK1/JNK signaling appears to play an important role in Cr(VI)-induced hepatocyte apoptosis and liver injury. This study should help improve our understanding of the mechanism of Cr(VI)-induced liver injury and provide support for future investigations on liver disease therapy.

ROCK inhibitor attenuates carbon blacks-induced pulmonary fibrosis in mice via Rho/ROCK/NF-kappa B pathway.

Exposure to carbon blacks (CBs) has been associated with the progression of pulmonary fibrosis, whereas the mechanism is still not clear. We therefore aimed to investigate the effect of RhoA/ROCK pathway on pulmonary fibrosis caused by CBs exposure. Western blot analysis indicated that CBs could promote the activation of RhoA/ROCK pathway and phosphorylation of p65 and IκBα in mice lung. However, ROCK inhibitor Y-27632 could attenuate phosphorylation levels of p65 and IκBα and restore histopathological changes of the lung tissue. Then, we evaluated the effect of RhoA/ROCK pathway on pulmonary fibrosis by detecting the expression levels of α-SMA, vimentin, and Collagen type-I (Col-I), which could be partly inhibited by Y-27632. It was assumed that inhibition of ROCK could be a promising therapeutic candidate for CBs-induced pulmonary fibrosis, which possibly through the blockage of RhoA/ROCK/NF-κB pathway.

PM2.5 collecting in a tire manufacturing plant affects epithelial differentiation of human umbilical cord derived mesenchymal stem cells by Wnt/ß-catenin pathway.

Mesenchymal stem cells (MSCs) can differentiate into pulmonary epithelial cells by Wnt/ß-catenin pathway and promote lung repair. However, whether fine particulate matter (PM2.5) could affect Wnt pathway and finally reduce the ability of MSCs to differentiate into epithelial cells is still unknown. This study aimed to investigate whether PM2.5 could inhibit the epithelial differentiation of human umbilical cord-derived MSCs cells (hUCMSCs) and the related underlying mechanism. hUCMSCs were incubated with different concentrations of PM2.5. Then, the cell viability, reactive oxygen species level, and single-cell sphere formation were assessed. The underlying mechanism of PM2.5 in epithelial differentiation of hUCMSCs was further evaluated by co-culturing hUCMSCs with A549 cells. Our results demonstrated that PM2.5 exposures could affect the expressions of ß-catenin and lung epithelial markers (zonula occludens-1 (ZO-1); cytokeratins 5 and 19) in the co-cultured hUCMSCs. The Wnt/ß-catenin pathway is involved in regulating the epithelial differentiation of MSCs. As expected, co-treatment with Wnt3a, which is the activator of the Wnt pathway, attenuated the downregulation of lung epithelial markers (ZO-1; cytokeratins 5 and 19) and paracrine factors (keratinocyte growth factor and hepatocyte growth factor) caused by PM2.5. Altogether, these results demonstrated that PM2.5 could affect the epithelial differentiation of hUCMSCs via the Wnt/ß-catenin pathway.

N-acetylcysteine attenuates PM2.5-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells.

While the effects of fine particulate matter (PM2.5) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of three germ layers. Thus, they are ideal resources for the reproductive toxicity assessment in vitro. In the present study, we investigated the effects of PM2.5 exposure on the oxidative stress and apoptosis of human ESCs (hESCs) and its possible mechanism. Our results showed that strong cytotoxicity high reactive oxygen species (ROS) level and fragmentation of nuclei were observed in the PM2.5-treated hESCs. Meanwhile, up-regulation of apoptosis as well as down-regulation of Nrf2 signaling pathway were also observed after PM2.5 treatment. However, we did not detect significant expression change or phosphorylation of Akt and Erk in PM2.5-treated hESCs. Interestingly, scavenging of PM2.5-induced ROS by N-acetylcysteine (NAC) could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. In conclusion, we demonstrate that PM2.5 is toxic to hESCs by inhibition of ROS-mediated Nrf2 pathway activity. Our findings suggest activation of Nrf2 pathway will help develop new strategies for the prevention and treatment of PM2.5-associated disease.

The effect of surface charge on the cytotoxicity and uptake of carbon quantum dots in human umbilical cord derived mesenchymal stem cells.

Carbon quantum dots (CQDs) are emerging as an ideal agent for efficient stem cell labeling. In current study, we synthesized a series of CQDs carrying different surface charges by changing the mass ratio of diammonium citrate (DC) and spermidine (Spd), and evaluated the effects of different surface charges on the cytotoxicity, cellular uptake, stability in human umbilical cord derived mesenchymal stem cells (hUCMSCs). We ascertained the optimal labeling time (24 h) and subtoxic concentration (50 µg/mL) of all different charged CQDs. Our results demonstrated that, although positively charged CQDs are more cytotoxic and have lower photoluminescence (PL) compared to negative CQDs, they still have higher labeling efficiency for their higher uptake capacity. We found that relatively weak positive surface charges enabled CQDs to possess good biocompatibility and labeling efficiency in hUCMSCs. This work will helpfully contribute to the design and optimization of CQDs for tracking stem cells and further benefit to clinical research and application.

Carbon black aggregates cause endothelial dysfunction by activating ROCK.

Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA. Moreover, transmission electron microscopic results showed that CBA entered cells through membrane enclosed vesicles. Rho-associated kinase (ROCK) is involved in regulating vascular diseases. Thus, we co-treated with the of ROCK inhibitor Y-27632 to study whether other adverse effects caused by CBA are related to activating ROCK. As expected, co-treatment with Y-27632 attenuated CBA-induced cytoskeletal damage, dysfunction of the endothelial barrier, and expression of inflammatory factors. Taken together, these results demonstrate that aggregated CBNs can cause endothelial dysfunction possibly by activating ROCK.

Consecutive evaluation of graphene oxide and reduced graphene oxide nanoplatelets immunotoxicity on monocytes.

The biocompatibilities of graphene-family nanomaterials (GFNs) should be thoroughly evaluated before their application in drug delivery and anticancer therapy. The present study aimed to consecutively assess the immunotoxicity of graphene oxide nanoplatelets (GONPs) and reduced GONPs (rGONPs) on THP-1 cells, a human acute monocytic leukemia cell line. GONPs induced the expression of antioxidative enzymes and inflammatory factors, whereas rGONPs had substantially higher cellular uptake rate, higher levels of NF-κB expression. These distinct toxic mechanisms were observed because the two nanomaterials differ in their oxidation state, which imparts different affinities for the cell membrane. Because GONPs have a higher cell membrane affinity and higher impact on membrane proteins compared with rGONPs, macrophages (THP-1a) derived from GONPs treated THP-1cells showed a severer effect on phagocytosis. By consecutive evaluation the effects of GONPs and rGONPs on THP-1 and THP-1a, we demonstrated that their surface oxidation states may cause GFNs to behave differently and cause different immunotoxic effects.

Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications.

Hypoglycemic activity and potential mechanism of a polysaccharide from the loach in streptozotocin-induced diabetic mice.

The present study was designed to investigate the hypoglycemic activity and the potential mechanisms of Misgurnus anguillicaudatus polysaccharide (MAP) in streptozotocin-induced diabetic mice. MAP oral administration significantly decreased the blood levels of glucose, TC, TG, LDL-C, and increased the blood levels of HDL-C and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. Moreover, MAP reversed the increased mRNA expressions of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Concurrently, MAP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-α, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated SOD and GPx activities in the serum of diabetic mice. Furthermore, MAP also significantly improved the blood markers of the impaired liver function and renal function in diabetic mice. Altogether, these results suggest that MAP may be a potential therapeutic option for type 1 diabetes.

Ventilator-associated pneumonia after cardiac surgery: a meta-analysis and systematic review.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is the most common and serious nosocomial infection that threatens patients who have undergone cardiac surgery. This article summarizes its clinical characteristics and provides theoretical evidence for prevention and treatment. METHODS: A literature search was conducted using PubMed, Embase, the Cochrane Library, and Web of Knowledge databases and by manual search. Data involving the prevalence, etiology, risk factors, or clinical outcomes were extracted for systematic review and meta-analysis. RESULTS: Eleven studies on VAP after cardiac surgery were included. When the results were merged the VAP rate was 21.27/1000 ventilator-days. The prevalence reached 6.37% of all patients and 35.2% of patients who were on mechanical ventilation for more than 48 hours. Among the isolated pathogens, Pseudomonas aeruginosa had the highest detection rate, with an average of 23.19%, followed by Staphylococcus aureus (20.15%), Haemophilus influenzae (19.53%), Acinetobacter baumannii (10.68%), Escherichia coli (10.18%), Klebsiella pneumoniae (9.52%), and Candida albicans (7.20%). Risk factors were also analyzed. We found that New York Heart Association cardiac function class IV, pulmonary hypertension, chronic obstructive pulmonary disease, peripheral vascular disease, renal disease, emergency surgery, intra-aortic balloon counterpulsation, cardiopulmonary bypass time, aortic crossclamp time, mechanical ventilation time, reintervention, and reintubation were closely related to the occurrence of VAP; there was no association with gender and diabetes mellitus. Once patients had VAP, mortality and length of stay in the intensive care unit were significantly increased. CONCLUSIONS: VAP in patients after cardiac surgery is common and has a poor prognosis. It is mainly caused by gram-negative bacteria, and could be affected by a series of factors.