CD1d protects against hepatocyte apoptosis in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.

Schistosome infection promotes osteoclast-mediated bone loss.

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.

A New Zn(II) Compound: Luminescent Property and Promoting Knee Cartilage Repair by Modulating Iron Death.

The hydrothermal reactions of bis{6-{5-methyl-1 H,7 H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one}}methane (L) and Zn(NO3)2·6H2O at 180 ℃ afforded a novel Zn(II) coordination polymer (CP), that is, {[Zn2(L)(µ2-O)2]·3H2O}n (1), which further characterized via Single crystal X-ray diffraction (SCXRD), elemental analysis (EA), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA). Besides, this CP reveals strong luminescence that may be caused by the charge transfer within the ligand. In biological study, the new compound was evaluated for its protective effect on chondrocytes. This compound significantly up-regulated GPX4 and down-regulated HO-1 mRNA levels, thereby inhibiting iron death in chondrocytes.

A Parallel Classification Model for Marine Mammal Sounds Based on Multi-Dimensional Feature Extraction and Data Augmentation.

Due to the poor visibility of the deep-sea environment, acoustic signals are often collected and analyzed to explore the behavior of marine species. With the progress of underwater signal-acquisition technology, the amount of acoustic data obtained from the ocean has exceeded the limit that human can process manually, so designing efficient marine-mammal classification algorithms has become a research hotspot. In this paper, we design a classification model based on a multi-channel parallel structure, which can process multi-dimensional acoustic features extracted from audio samples, and fuse the prediction results of different channels through a trainable full connection layer. It uses transfer learning to obtain faster convergence speed, and introduces data augmentation to improve the classification accuracy. The k-fold cross-validation method was used to segment the data set to comprehensively evaluate the prediction accuracy and robustness of the model. The evaluation results showed that the model can achieve a mean accuracy of 95.21% while maintaining a standard deviation of 0.65%. There was excellent consistency in performance over multiple tests.

Hepatocyte CD1d protects against liver immunopathology in mice with schistosomiasis japonica.

Schistosomiasis is a neglected tropical disease with over 250 million people infected worldwide. The main clinically important species Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum) cause inflammatory responses against tissue-trapped eggs, resulting in formation of granulomas mainly in host liver. Persistent granulomatous response results in severe fibrosis in the liver, leading to irreversible impairment of the liver and even death of the host. CD1d, a highly conserved MHC class I-like molecule, is expressed by both haematopoietic and non-haematopoietic cells. CD1d on antigen-presenting cells (APCs) of haematopoietic origin presents pathogen-derived lipid antigens to natural killer T (NKT) cells, which enables them to rapidly produce large amounts of various cytokines and facilitate CD4+ T helper (Th) cell differentiation upon invading pathogens. Noteworthy, hepatocytes of non-haematopoietic origin have recently been shown to be involved in maintaining liver NKT cell homeostasis through a CD1d-dependent manner. However, whether hepatocyte CD1d-dependent regulation of NKT cell homeostasis also modulates CD4+ Th cell responses and liver immunopathology in murine schistosomiasis remains to be addressed. Here, we show in mice that CD1d expression on hepatocytes was decreased dramatically upon S. japonicum infection, accompanied by increased NKT cells, as well as upregulated Th1 and Th2 responses. Overexpression of CD1d in hepatocytes significantly decreased local NKT numbers and cytokines (IFN-γ, IL-4, IL-13), concomitantly with downregulation of both Th1 and Th2 responses and alleviation in pathological damage in livers of S. japonicum-infected mice. These findings highlight the potential of hepatocyte CD1d-targeted therapies for liver immunopathology control in schistosomiasis.

Identification of miRNAs and their target genes in genic male sterility lines in Brassica napus by small RNA sequencing.

BACKGROUND: Brassica napus is the third leading source of edible oil in the world. Genic male sterility (GMS) lines provide crucial material for harnessing heterosis for rapeseed. GMS lines have been used successfully for rapeseed hybrid production in China. MicroRNAs (miRNAs) play crucial regulatory roles in various plant growth, development, and stress response processes. However, reports on miRNAs that regulate the pollen development of GMS lines in B. napus are few. RESULTS: In this study, 12 small RNA and transcriptome libraries were constructed and sequenced for the flower buds from the fertile and sterile lines of two recessive GMS (RGMS) lines, namely, "6251AB" and "6284AB". At the same time, 12 small RNA and transcriptome libraries were also constructed and sequenced for the flower buds from the fertile and sterile lines of two dominant GMS (DGMS) lines, namely, "4001AB" and "4006AB". Based on the results, 46 known miRNAs, 27 novel miRNAs on the other arm of known pre-miRNAs, and 44 new conserved miRNAs were identified. Thirty-five pairs of novel miRNA-3p/miRNA-5p were found. Among all the identified miRNAs, fifteen differentially expressed miRNAs with over 1.5-fold change between flower buds of sterile and fertile lines were identified, including six differentially expressed miRNAs between "4001A" and "4001B", two differentially expressed miRNAs between "4006A" and "4006B", four differentially expressed miRNAs between "6251A" and "6251B", and ten differentially expressed miRNAs between "6284A" and "6284B". The correlation analysis of small RNA and transcriptome sequencing was conducted. And 257 candidate target genes were predicted for the 15 differentially expressed miRNAs. The results of 5' modified RACE indicated that BnaA09g48720D, BnaA09g11120D, and BnaCnng51960D were cleaved by bna-miR398a-3p, bna-miR158-3p and bna-miR159a, respectively. Among the differentially expressed miRNAs, miR159 was chosen to analyze its function. Overexpression of bna-miR159 in Arabidopsis resulted in decreased seed setting rate, and shortened siliques, illustrating that miR159 may regulate the fertility and silique development in rapeseed. CONCLUSIONS: Our findings provide an overview of miRNAs that are potentially involved in GMS and pollen development. New information on miRNAs and their related target genes are provided to exploit the GMS mechanism and reveal the miRNA networks in B. napus.

Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during Schistosoma japonicum infection.

Schistosomiasis affects at least 200 million people in tropical and subtropical areas. The major pathology of schistosomiasis is egg-induced liver granuloma characterized by an eosinophil-rich inflammatory infiltration around the eggs, which subsequently leads to hepatic fibrosis and circulatory impairment in host. However, the mechanisms how eosinophils are recruited into the liver, which are crucial for the better understanding of the mechanisms underlying granuloma formation and control of schistosomiasis, remain unclear. In this study, we showed that follicular helper T (Tfh) cells participate in recruitment of eosinophils into liver partially by producing CXCL12 during schistosome infection. Our findings uncovered a previously unappreciated role of Tfh cells in promotion of the development of liver granuloma in schistosomiasis, making Tfh-CXCL12-eosinophil axis a potential target for intervention of schistosomiasis.

Tunable plasmon-induced transparency in graphene metamaterials with ring-semiring pair coupling structures.

In this paper, a tunable graphene metamaterial with a ring-semiring pair coupling structure was proposed to achieve the plasmon-induced transparency (PIT) effect at terahertz frequencies, and its high-sensitivity sensor performances were simulated. We change the resonant frequency of the PIT window by adjusting the Fermi energy of the graphene or the relative distance of the geometry parameters. When the refractive index of the dielectric inserted into the structure changes, the spectral transmission of the metamaterial structure changes simultaneously. Therefore, the results of this study provide a new, to the best of our knowledge, method for making adjustable light sensors.

Downregulation of serum miR-194 predicts poor prognosis in osteosarcoma patients.

BACKGROUND: Circulating microRNAs (miRNAs) have promising potential as diagnostic and prognostic biomarkers for osteosarcoma. This study aimed to explore the expression pattern of serum miR-194 and its potential clinical value in patients with osteosarcoma. METHODS: Messenger RNA was isolated from serum sample from 124 osteosarcoma patients, 60 periostitis patients and 60 healthy volunteers. The serum miR-194 level was then examined by quantitative real-time polymerase chain reaction (qRT-PCR). The bioinformatic analysis of the downstream targets of miR-194 was also performed. RESULTS: The results showed serum miR-194 levels were significantly decreased in osteosarcoma patients compared to those in periostitis patients or healthy controls. Receiver-operating characteristic (ROC) analysis demonstrated that serum miR-194 had a good diagnostic value for identifying osteosarcoma subjects from periostitis patients and normal controls. In addition, serum miR-194 levels were dramatically increased following surgery in osteosarcoma cases. Moreover, low serum miR-194 expression was strongly correlated with positive metastasis and advanced clinical stage, as well as worse survival. Furthermore, serum miR-194 was confirmed to be an independent prognostic biomarker for osteosarcoma. Bioinformatic analysis showed that the downstream targeted genes of miR-194 were closely associated with cancer initiation and development. CONCLUSION: In conclusion, our results have demonstrated that serum miR-194 might serve as a novel and promising biomarker for the detection and prognosis of osteosarcoma.

Repair of non-traumatic femoral head necrosis by marrow core decompression with bone grafting and porous tantalum rod implantation.

OBJECTIVE: To compare the clinical effects of marrow core decompression with bone grafting and marrow core decompression with porous tantalum rod implantation in treating avascular necrosis of non-traumatic femoral head. METHODS: This prospective study selected 60 patients (74 hips) with avascular necrosis of femoral head admitted to Daping Hospital from January 2018 to March 2019. According to treatment methods, the 60 patients were randomly divided into two groups, i.e. 30 patients in one group were treated by marrow core decompression with bone grafting, and the other 30 patients in the other group were treated with marrow core decompression and porous tantalum rod implantation. RESULTS: All implantation treatments were successful. No significant difference was found in surgical duration, hemorrhage volume and duration of hospitalization stay between the two groups during follow-up. All Harris scores were significantly improved (P<0.05) following treatment compared to those before treatment. The Harris score of patients treated with porous tantalum rod implantation was higher than that of patients treated with bone grafting (P<0.05) after 12 months following treatment and such a difference was significant. CONCLUSION: The combination of marrow core decompression and porous tantalum rod implantation can better improve the functions of hip joints with early femoral head necrosis than marrow core decompression with bone grafting, and can also prevent articular cartilage from collapsing gradually.

Aquaporin-4 deficiency reduces TGF-ß1 in mouse midbrains and exacerbates pathology in experimental Parkinson's disease.

Aquaporin-4 (AQP4), the main water-selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model, AQP4-deficient (AQP4-/- ) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+ )-positive neurons than did wild-type AQP4 (AQP4+/+ ) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor-ß1 (TGF-ß1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4-/- mice after MPTP treatment. Furthermore, the lower level of TGF-ß1 in AQP4-/- mice partially resulted from impairment of its generation by astrocytes; reduced TGF-ß1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH+ neurons in AQP4-/- mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4-mediated immune regulation.

The IL-33-ST2-MyD88 axis promotes regulatory T cell proliferation in the murine liver.

Hepatic Foxp3+ Treg cells are crucial for maintaining local immune homeostasis in the liver. However, the environmental cues required for hepatic Treg cell homeostasis are unclear. In this study, we showed that the IL-33 receptor ST2 was preferentially expressed on Treg cells in the mouse liver, but it was more lowly expressed in the spleen, mesenteric lymph nodes, and blood. More importantly, we found that IL-33 promoted the proliferation of hepatic Treg cells through myeloid differentiation factor MyD88 signaling concomitant with increased cyclin-dependent kinase 4 and cyclin D1 expression. These results suggest that IL-33 is a potential tissue-specific factor controlling Treg cell homeostasis via increased Treg proliferation in the liver.

IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum-infected mice.

In schistosomiasis japonica and mansoni, parasite eggs trapped in host liver elicit severe liver granulomatous inflammation that subsequently leads to periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages are critical for granuloma formation and the development of liver fibrosis during schistosomiasis. However, whether the aberrant regulation of macrophage autophagy has an effect on the development of liver immunopathology in schistosomiasis remains to be elucidated. In this study, we showed that Schistosoma japonicum (S. japonicum) egg antigen (SEA)-triggered macrophage autophagy limited the development of pathology in host liver. However, engagement of IL-7 receptor (IL-7R/CD127) on macrophages by S. japonicum infection-induced IL-7 significantly suppressed SEA-triggered macrophage autophagy, which led to an enhanced liver pathology. In addition, anti-IL-7 neutralizing antibody or anti-CD127 blocking antibody treatment increased macrophage autophagy and suppressed liver pathology. Finally, we demonstrated that IL-7 protects macrophage against SEA-induced autophagy through activation of AMP-activated protein kinase (AMPK). Our study reveals a novel role for IL-7 in macrophage autophagy and identifies AMPK as a novel downstream mediator of IL-7-IL-7R signalling and suggests that manipulation of macrophage autophagy by targeting IL-7-IL-7R signalling may have the potential to lead to improved treatment options for liver pathogenesis in schistosomiasis.

The regulation of regulation: interleukin-10 increases CD4+ CD25+ regulatory T cells but impairs their immunosuppressive activity in murine models with schistosomiasis japonica or asthma.

CD4+ CD25+ Foxp3+ regulatory T (Treg) cells play an important role in maintaining immune homeostasis. Interleukin-10 (IL-10), a cytokine with anti-inflammatory capacities, also has a critical role in controlling immune responses. In addition, it is well known that production of IL-10 is one of the suppression mechanisms of Treg cells. However, the action of IL-10 on Treg cells themselves remains insufficiently understood. In this study, by using a Schistosoma japonicum-infected murine model, we show that the elevated IL-10 contributed to Treg cell induction but impaired their immunosuppressive function. Our investigations further suggest that this may relate to the up-regulation of serum transforming growth factor (TGF-ß) level but the decrease in membrane-bound TGF-ß of Treg cells by IL-10 during S. japonicum infection. In addition, similar IL-10-mediated regulation on Treg cells was also confirmed in the murine model of asthma. In general, our findings identify a previously unrecognized opposing regulation of IL-10 on Treg cells and provide a deep insight into the precise regulation in immune responses.

SjHSP60 induces CD4+ CD25+ Foxp3+ Tregs via TLR4-Mal-drived production of TGF-ß in macrophages.

CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) play a pivotal role in limiting immunopathological damage to host organs after schistosome infection. Transforming growth factor-ß (TGF-ß) is an essential factor for the periphery conversion of CD4+ CD25- T cells into CD4+ CD25+ Foxp3+ Tregs by inducing the key transcription factor Foxp3. Antigen presenting cells (APCs), which highly express TGF-ß, are involved in parasite antigen-induced Treg conversion in peripheral. However, the mechanisms underlying high TGF-ß induction in APCs by parasite antigens remain to be clarified during schistosome infection. Here, we demonstrated that Schistosoma japonicum stress protein, heat shock protein 60 (SjHSP60), promoted TGF-ß production in macrophages (Mφ). Furthermore, we showed that activation of TLR4-Mal (MyD88 adaptor-like protein) signaling by SjHSP60 is necessary for induction of TGF-ß expression in Mφ, which subsequently promoted Treg induction. Our results not only demonstrate a novel mechanism of TGF-ß production in Mφ for inducing Tregs in mice with schistosomiasis, but also allude to the possibility of targeting parasite stress protein for potential therapeutics.

Development and validation of the Alzheimer's prevention beliefs measure in a multi-ethnic cohort-a behavioral theory approach.

Background: Understanding health beliefs and how they influence willingness will enable the development of targeted curricula that maximize public engagement in Alzheimer's disease (AD) risk reduction behaviors. Methods: Literature on behavioral theory and community input was used to develop and validate a health beliefs survey about AD risk reduction among 428 community-dwelling adults. Principal component analysis was performed to assess internal consistency. Linear regression was performed to identify key predictors of Willingness to engage in AD risk reduction behaviors. Results: The measure as well as the individual scales (Benefits, Barriers, Severity, Susceptibility and Social Norm) were found to be internally consistent. Overall, as Benefits and Barriers scores increased, Willingness scores also increased. Those without prior AD experience or family history had lower willingness scores. Finally, we observed an interaction between age and norms, suggesting that social factors related to AD prevention may differentially affect people of different ages. Conclusions: The Alzheimer Prevention Beliefs Measure provides assessment of several health belief factors related to AD prevention. Age, Family History, Logistical Barriers and total Benefits are significant determinants of willingness to engage in AD risk reduction behaviors, such as seeing a doctor or making a lifestyle change.

Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

Increased Frequency of Th17 Cells in Children With Mycoplasma pneumoniae Pneumonia.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae, MP) is recognized globally as a significant cause of primary atypical pneumonia in humans, particularly in children. Overzealous host immune responses are viewed as key mediators of the pathogenesis of M. pneumoniae infection. Although Th17 cells have been identified as key modulators in the clearance of pathogens and induction of autoimmunity caused by excessive immune responses, little is known about the role of Th17 cells in patients with M. pneumoniae infection. METHODS: The percentages of T cells, CD4+ T cells and Th17 cells in children with M. pneumoniae infection were measured by flow cytometry. RESULTS: We documented an increased frequency of Th17 cells in children with M. pneumoniae infection. Furthermore, we found a significantly higher percentage of Th17 cells in M. pneumoniae-infected children with extrapulmonary manifestations, compared with children without extrapulmonary manifestations. In addition, patients who experienced a short course of Mycoplasma pneumoniae pneumonia (MPP) showed an increase in the percentage of Th17 cells. CONCLUSION: Our findings suggest that Th17 cells may be involved in the clearance of M. pneumoniae during an acute infection. Excessive Th17 cell responses may also contribute to the immuno-pathological damage observed during persistent infection.

MIR-155 PROMOTES ACUTE ORGAN INJURY IN LPS-INDUCED ENDOTOXEMIC MICE BY ENHANCING CCL-2 EXPRESSION IN MACROPHAGES.

ABSTRACT: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Macrophages play important roles in the inflammatory process of sepsis by secreting chemokines. Chemokine (CC-motif) ligand 2 (CCL-2) is one of the main proinflammatory chemokines secreted by macrophages that plays a critical role in the recruitment of more monocytes and macrophages to the sites of injury in sepsis, but the mechanisms that regulate CCL-2 expression in macrophages during sepsis are still unknown. In the present study, by using the LPS-induced endotoxemia model, we found that LPS induced the expression of microRNA (miR)-155 and CCL-2 in endotoxemic mice and RAW264.7 cells. MiR-155 mimics or miR-155 inhibitor treatment experiment suggested that miR-155 was sufficient to increase LPS-induced CCL-2 expression in macrophages, but miR-155 was not the only factor promoting CCL-2 expression. We further demonstrated that miR-155-induced increase of CCL-2 promoted chemotaxis of additional macrophages, which subsequently enhanced lung injury in endotoxemic mice. Serum/glucocorticoid regulated kinase family member 3 (SGK3), a potential target of miR-155, was identified by RNA sequencing and predicted by TargetScan and miRDB. We further confirmed miR-155 regulated SGK3 to increase LPS-induced CCL-2 by using miR-155 mimics and SGK3 overexpression. Thus, our study demonstrates that miR-155 targets SGK3 to increase LPS-induced CCL-2 expression in macrophages, which promotes macrophage chemotaxis and enhances organs injury during endotoxemia. Our study contributed to a better understanding of the mechanisms underlying the inflammatory response during sepsis.

A retrospective case study of successful translational research: Cardiovascular disease risk assessment, experiences in community engagement.

In underserved communities across New York City, uninsured adults encounter a greater risk of cardiovascular disease (CVD) and diabetes. The Heart-to-Heart Community Outreach Program (H2H) addresses these disparities by screening for CVD risk factors, identifying healthcare access barriers, and fostering community engagement in translational research at the Weill Cornell Medicine Clinical and Translational Science Award (CTSA) hub. Screening events are hosted in partnership with faith-based institutions. Participants provide a medical history, complete a survey, and receive counseling by clinicians with referrals for follow-up care. This study aims to quantify H2H screening participant health status; identify socioeconomic, health access, and health-related barriers disproportionately promoting the onset of CVD and diabetes; and develop long-term community partnerships to enable underserved communities to influence activities across the translational research spectrum at our CTSA hub. The population served is disproportionately non-white, and uninsured, with many low-income and underserved individuals. The program was developed in partnership with our Community Advisory Board to empower this cohort to make beneficial lifestyle changes. Leveraging partnerships with faith-based institutions and community centers in at-risk New York City neighborhoods, H2H addresses the increasing burden of diabetes and CVD risk factors in vulnerable individuals while promoting community involvement in CTSA activities, serving as a model for similar initiatives.