Relative efficacy of antibody-drug conjugates and other anti-HER2 treatments on survival in HER2-positive advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC. METHODS: Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis. RESULTS: Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49-0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72-0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable. CONCLUSION: Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment.

The potential role of hydrogen sulfide in cancer cell apoptosis.

For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Corticosteroid in non-COVID-19 induced community-acquired pneumonia, a meta-analysis.

BACKGROUND: Corticosteroid treatment in non-COVID-19 induced Community-acquired pneumonia (CAP) remains inconclusive. OBJECTIVES: We aimed to assess the role of corticosteroid treatment in CAP. METHODS: We conducted a comprehensive search of online databases, including PubMed, Embase, and Cochrane, to identify articles published from January 1, 2000, to May 5, 2023. Double-blind RCTs were selected. Two authors screened studies and extracted data. The evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We analyzed data from 12 RCTs, involving 2446 patients. Corticosteroids therapy may reduce short-term mortality in patients with severe CAP (sCAP) and shorten the hospital length of stay in patients with CAP. Furthermore, corticosteroids treatment can decrease the risk of requiring mechanical ventilation, developing septic shock and multiple organ dysfunction syndrome (MODS). There were no significant differences between the corticosteroid and control groups concerning gastrointestinal bleeding and nosocomial infection. The use of corticosteroids could increase the risk of hyperglycemia. CONCLUSION: Corticosteroid treatment for sCAP has the potential to provide benefits in reducing short-term mortality, but this conclusion necessitates more evidence. Besides, we found no evidence that strongly prevents us from using corticosteroids in patients with sCAP or those at risk of progressing to sCAP.

Gestational diabetes and risk of perinatal depression in low- and middle-income countries: a meta-analysis.

Background: The relationship between gestational diabetes (GDM) and the risk of depression has been thoroughly investigated in high-income countries on their financial basis, while it is largely unexplored in low- and middle- income countries. This meta-analysis aims to assess how GDM influences the risk of perinatal depression by searching multiple electronic databases for studies measuring the odds ratios between them in low- and middle-income countries. Methods: Two independent reviewers searched multiple electronic databases for studies that investigated GDM and perinatal mental disorders on August 31, 2023. Pooled odds ratios (ORs) and confidence intervals (CIs) were calculated using the random effect model. Subgroup analyses were further conducted based on the type of study design and country income level. Results: In total, 16 observational studies met the inclusion criteria. Only the number of studies on depression (n=10) satisfied the conditions to conduct a meta-analysis, showing the relationship between mental illness and GDM has been overlooked in low- and middle-income countries. Evidence shows an elevated risk of perinatal depression in women with GDM (pooled OR 1.92; 95% CI 1.24, 2.97; 10 studies). The increased risk of perinatal depression in patients with GDM was not significantly different between cross-sectional and prospective design. Country income level is a significant factor that adversely influences the risk of perinatal depression in GDM patients. Conclusion: Our findings suggested that women with GDM are vulnerable to perinatal depressive symptoms, and a deeper understanding of potential risk factors and mechanisms may help inform strategies aimed at prevention of exposure to these complications during pregnancy.

Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma.

Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 µM for inhibiting sphere formation and 0.5-15 µM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.

IL-33/ST2L signaling alleviates diabetic nephropathy by regulating endoplasmic reticulum stress and apoptosis.

OBJECTIVE: Diabetic nephropathy (DN) is a serious chronic complication of diabetes mellitus (DM). Endoplasmic reticulum (ER) stress is an important factor in the regulation of pathological processes in DN, and excessive ER stress can lead to apoptosis. Although the IL-33/ST2 axis is known to be involved in diabetic kidney disease or related nephropathy, its role and molecular mechanisms remain poorly understood in terms of DN. The purpose of this study was to investigate the effects of IL-33/ST2 signaling on DN and to characterize the roles that ER stress and apoptosis play in DN. METHODS: To investigate this study, mice were randomly assigned into DN (induced by 0.1% STZ) and Control groups. Biochemical indices (FBG, BUN, UPR, UCE) were measured in serum and urine samples to reflect blood glucose and kidney damage. Quantitative real-time PCR, western blot, and immunofluorescence were used to assess gene and protein expression of the IL-33/ST2 axis and ER stress relative signaling molecule. Apoptosis was analyzed by flow cytometry. RESULTS: IL-33 levels are significantly increased in the kidneys of patients and mice with DN. Double immunofluorescence staining showed that IL-33 colocalized with CD31-positive endothelial cells. Treatment with IL-33 attenuated kidney injury in Streptozotocin (STZ)-treated mice. In vitro, we showed that IL-33 attenuated ER stress and apoptosis in glomerular endothelial cells. However, sST2 treatment significantly reversed these effects of IL-33. CONCLUSION: Together, these data suggest that IL-33/ST2 signaling mitigates STZ-induced renal damage, partly at least, by suppressing ER stress and apoptosis. Therefore, IL-33 may be an effective therapeutic target in DN.

Clinical Timing-Sequence Warning Models for Serious Bacterial Infections in Adults Based on Machine Learning: Retrospective Study.

BACKGROUND: Serious bacterial infections (SBIs) are linked to unplanned hospital admissions and a high mortality rate. The early identification of SBIs is crucial in clinical practice. OBJECTIVE: This study aims to establish and validate clinically applicable models designed to identify SBIs in patients with infective fever. METHODS: Clinical data from 945 patients with infective fever, encompassing demographic and laboratory indicators, were retrospectively collected from a 2200-bed teaching hospital between January 2013 and December 2020. The data were randomly divided into training and test sets at a ratio of 7:3. Various machine learning (ML) algorithms, including Boruta, Lasso (least absolute shrinkage and selection operator), and recursive feature elimination, were utilized for feature filtering. The selected features were subsequently used to construct models predicting SBIs using logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) with 5-fold cross-validation. Performance metrics, including the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), accuracy, sensitivity, and other relevant parameters, were used to assess model performance. Considering both model performance and clinical needs, 2 clinical timing-sequence warning models were ultimately confirmed using LR analysis. The corresponding predictive nomograms were then plotted for clinical use. Moreover, a physician, blinded to the study, collected additional data from the same center involving 164 patients during 2021. The nomograms developed in the study were then applied in clinical practice to further validate their clinical utility. RESULTS: In total, 69.9% (661/945) of the patients developed SBIs. Age, hemoglobin, neutrophil-to-lymphocyte ratio, fibrinogen, and C-reactive protein levels were identified as important features by at least two ML algorithms. Considering the collection sequence of these indicators and clinical demands, 2 timing-sequence models predicting the SBI risk were constructed accordingly: the early admission model (model 1) and the model within 24 hours of admission (model 2). LR demonstrated better stability than RF and XGBoost in both models and performed the best in model 2, with an AUC, accuracy, and sensitivity of 0.780 (95% CI 0.720-841), 0.754 (95% CI 0.698-804), and 0.776 (95% CI 0.711-832), respectively. XGBoost had an advantage over LR in AUC (0.708, 95% CI 0.641-775 vs 0.686, 95% CI 0.617-754), while RF achieved better accuracy (0.729, 95% CI 0.673-780) and sensitivity (0.790, 95% CI 0.728-844) than the other 2 approaches in model 1. Two SBI-risk prediction nomograms were developed for clinical use based on LR, and they exhibited good performance with an accuracy of 0.707 and 0.750 and a sensitivity of 0.729 and 0.927 in clinical application. CONCLUSIONS: The clinical timing-sequence warning models demonstrated efficacy in predicting SBIs in patients suspected of having infective fever and in clinical application, suggesting good potential in clinical decision-making. Nevertheless, additional prospective and multicenter studies are necessary to further confirm their clinical utility.

Evaluation of Chlamydia trachomatis screening from the perspective of health economics: a systematic review.

Background: Most Chlamydia trachomatis (CT) infections are asymptomatic. The infection can persist and lead to severe sequelae. Therefore, screening for CT can primarily prevent serious sequelae. Aim: To systematically evaluate CT screening from the perspective of health economics, summarize previous findings from different target populations, and make practical recommendations for developing local CT screening strategies. Methods: PubMed, Web of Science, Embase, Cochran Library, and National Health Service Economic Evaluation Database (Ovid) were searched from January 1, 2000, to March 4, 2023. Studies reporting the cost-effectiveness, cost-benefit, or cost-utility of CT screening were eligible to be included. A narrative synthesis was used to analyze and report the results following the PRISMA guidelines. The Consensus on Health Economic Criteria (CHEC) list was used to assess the methodological quality of included studies. Results: Our review finally comprised 39 studies addressing four populations: general sexually active people (n = 25), pregnant women (n = 4), women attending STD and abortion clinics (n = 4), and other high-risk individuals (n = 6). The total number of participants was ~7,991,198. The majority of studies assessed the cost-effectiveness or cost-utility of the screening method. The results showed that the following screening strategies may be cost-effective or cost-saving under certain conditions: performing CT screening in young people aged 15-24 in the general population, military recruits, and high school students; incorporating CT screening into routine antenatal care for pregnant women aged 15-30; opportunistic CT screening for women attending STD and abortion clinics; home-obtained sampling for CT screening using urine specimens or vaginal swab; performing CT screening for 14-30-year-old people who enter correctional institutions (i.e., jail, detention) as soon as possible; providing CT screening for female sex workers (FSWs) based on local incidence and prevalence; adding routine CT screening to HIV treatment using rectal samples from men who have sex with men (MSM). Conclusion: We found that CT screening in general sexually active people aged 15-24, military recruits, high school students, pregnant women aged 15-30, women attending STD and abortion clinics, people entering jail, detention, FSWs, and MSM has health economic value. Due to the different prevalence of CT, diversities of economic conditions, and varying screening costs among different populations and different countries, regions, or settings, no uniform and standard screening strategies are currently available. Therefore, each country should consider its local condition and the results of health economic evaluations of CT screening programs in that country to develop appropriate CT screening strategies.

Identification and validation of potential hypoxia-related genes associated with coronary artery disease.

Introduction: Coronary artery disease (CAD) is one of the most life-threatening cardiovascular emergencies with high mortality and morbidity. Increasing evidence has demonstrated that the degree of hypoxia is closely associated with the development and survival outcomes of CAD patients. However, the role of hypoxia in CAD has not been elucidated. Methods: Based on the GSE113079 microarray dataset and the hypoxia-associated gene collection, differential analysis, machine learning, and validation of the screened hub genes were carried out. Results: In this study, 54 differentially expressed hypoxia-related genes (DE-HRGs), and then 4 hub signature genes (ADM, PPFIA4, FAM162A, and TPBG) were identified based on microarray datasets GSE113079 which including of 93 CAD patients and 48 healthy controls and hypoxia-related gene set. Then, 4 hub genes were also validated in other three CAD related microarray datasets. Through GO and KEGG pathway enrichment analyses, we found three upregulated hub genes (ADM, PPFIA4, TPBG) were strongly correlated with differentially expressed metabolic genes and all the 4 hub genes were mainly enriched in many immune-related biological processes and pathways in CAD. Additionally, 10 immune cell types were found significantly different between the CAD and control groups, especially CD8 T cells, which were apparently essential in cardiovascular disease by immune cell infiltration analysis. Furthermore, we compared the expression of 4 hub genes in 15 cell subtypes in CAD coronary lesions and found that ADM, FAM162A and TPBG were all expressed at higher levels in endothelial cells by single-cell sequencing analysis. Discussion: The study identified four hypoxia genes associated with coronary heart disease. The findings provide more insights into the hypoxia landscape and, potentially, the therapeutic targets of CAD.

Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common fatal cancer worldwide, patients with HCC have a high mortality rate and poor prognosis. PANoptosis is a novel discovery of programmed cell death associated with cancer development. However, the role of PANoptosis in HCC remains obscure. In this study, we enrolled 274 PANoptosis-related genes (PANRGs) and screened 8 genes to set up a prognostic model. A previous scoring system calculated PANscore was utilized to quantify the individual risk level of each HCC patient, and the reliability of the prognostic model has been validated in an external cohort. Nomogram constructed with PANscore and clinical characteristics were used to optimize individualized treatment for each patient. Single-cell analysis revealed a PANoptosis model associated with tumor immune cell infiltration, particularly natural killer (NK) cells. Further exploration of hub genes and assessment of the prognostic role of these 4 hub genes in HCC by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). In conclusion, we evaluated a PANoptosis-based prognostic model as a potential prognostic biomarker for HCC patients.

Oxovanadium(v)-catalyzed oxidative cross-coupling of enolates using O2 as a terminal oxidant.

The oxovanadium(v)-catalyzed oxidative cross-coupling of enolates using O2 as a terminal oxidant is reported, where a boron enolate and a silyl enol ether were employed as enolates. The redox behavior of V(v/iv) in this reaction under O2 was investigated by ESR and 51V NMR experiments.

Landscape genomics predicts climate change-related genetic offset for the widespread Platycladus orientalis (Cupressaceae).

Understanding and quantifying populations' adaptive genetic variation and their response to climate change are critical to reforestation's seed source selection, forest management decisions, and gene conservation. Landscape genomics combined with geographic and environmental information provide an opportunity to interrogate forest populations' genome-wide variation for understanding the extent to which evolutionary forces shape past and contemporary populations' genetic structure, and identify those populations that may be most at risk under future climate change. Here, we used genotyping by sequencing to generate over 11,000 high-quality variants from Platycladus orientalis range-wide collection to evaluate its diversity and to predict genetic offset under future climate scenarios. Platycladus orientalis is a widespread conifer in China with significant ecological, timber, and medicinal values. We found population structure and evidences of isolation by environment, indicative of adaptation to local conditions. Gradient forest modeling identified temperature-related variables as the most important environmental factors influencing genetic variation and predicted areas with higher risk under future climate change. This study provides an important reference for forest resource management and conservation for P. orientalis.

Genome-Wide Variant Identification and High-Density Genetic Map Construction Using RADseq for Platycladus orientalis (Cupressaceae).

Platycladus orientalis is an ecologically important native conifer in Northern China and exotic species in many parts of the world; however, knowledge about the species' genetics and genome are very limited. The availability of well-developed battery of genetic markers, with large genome coverage, is a prerequisite for the species genetic dissection of adaptive attributes and efficient selective breeding. Here, we present a genome-wide genotyping method with double-digestion restriction site associated DNA sequencing (ddRAD-seq) that is effective in generating large number of Mendelian markers for genome mapping and other genetic applications. Using 139 megagametophytes collected from a single mother tree, we assembled 397,226 loci, of which 108,683 (27.4%) were polymorphic. After stringent filtering for 1:1 segregation ratio and missing rate of <20%, the remaining 23,926 loci (22% of the polymorphic loci) were ordered into 11 linkage groups (LGs) and distributed across 7,559 unique positions, with a total map length of 1,443 cM and an average spacing of 0.2 cM between adjacent unique positions. The 11 LGs correspond to the species' 11 haploid genome chromosome number. This genetic map is among few high-density maps available for conifers to date, and represents the first genetic map for P. orientalis The information generated serves as a solid foundation not only for marker-assisted breeding efforts, but also for comparative conifer genomic studies.

Loss of homeoprotein Msx1 and Msx2 leading to athletic and kinematic impairment related to the increasing neural excitability of neurons in aberrant neocortex in mice.

Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2fl/fl). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion. In addition, electrophysiological tests revealed the aberrant action potential parameters of deep pyramidal neurons in Nestin-Cre;Msx1,2 fl/fl mice, which may be related with the ethology impairment displayed in further experiments. We discovered Nestin-Cre;Msx1,2 fl/fl mice had severe impairment in their athletic ability and kinematic learning ability in rotate test, and exhibited hyperactivity in open-field test. Above all, our results revealed that deletion of homeoproteins Msx1 and Msx2 could lead to behavioral disorders and suggested that Msx1 and Msx2 played a crucial role in regulating the development and function of the neocortex. In addition, our current research provided a new mouse model for understanding the pathogenesis of human central nervous system disease.

Development of novel EST-SSR markers for Ephedra sinica (Ephedraceae) by transcriptome database mining.

PREMISE OF THE STUDY: Ephedra sinica (Ephedraceae) is a gymnosperm shrub with a wide distribution across Central and Eastern Asia. It is widely cultivated as a medicinal plant, but its wild populations are monitored to determine whether protection is needed. METHODS AND RESULTS: Thirty-six microsatellite markers, including 11 polymorphic markers, were developed from E. distachya RNA-Seq data deposited in the National Center for Biotechology Information dbEST database. Among 100 genotyped E. sinica individuals originating from five different population groups, the allele number ranged from three to 22 per locus. Levels of observed and expected heterozygosity ranged from 0 to 0.866 (average 0.176) and 0 to 0.876 (average 0.491), respectively. Allelic polymorphism information content ranged from 0.000 to 0.847 (average 0.333). Cross-species amplifications were successfully conducted with two related Ephedra species for all 11 di- or trinucleotide simple sequence repeats. CONCLUSIONS: This study provides the first set of microsatellite markers for genetic monitoring and surveying of this medicinal plant.

Development of high transferability cpSSR markers for individual identification and genetic investigation in Cupressaceae species.

Given the low substitution rate in plastomes, the polymorphic and codominant nature of chloroplast SSRs (cpSSRs) makes them ideal markers, complementing their nuclear counterpart. In Cupressaceae, cpSSRs are mostly paternally inherited, thus, they are useful in mating systems and pollen flow studies. Using e-PCR, 92 SSR loci were identified across six Cupressaceae plastomes, and primers were designed for 26 loci with potential interspecific transferability. The 26 developed cpSSRs were polymorphic in four genera, Platycladus, Sabina, Juniperus, and Cupressus and are suitable for Cupressaceae molecular genetic studies and utilization. We genotyped 192 Platycladus orientalis samples from a core breeding population using 10 of the developed cpSSRs and 10 nuclear SSRs, and these individuals were identified with high confidence. The developed cpSSRs can be used in (1) a marker-assisted breeding scheme, specifically when paternity identification is required, (2) population genetics investigations, and (3) biogeography of Cupressaceae and unraveling the genetic relationships between related species.

The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair.

Combinations of fibroblasts (Fbs) and corresponding epithelial cells have been widely used in many tissues, such as the skin and breast tissues, to augment tissue repair and remodeling. Recently, a large amount of new data has indicated that nerve Fbs play critical roles in Schwann cells (SCs) and axons in vitro. However, little is known regarding the effects of co-transplanting nerve Fbs and SCs on peripheral nerve repair in vivo. The aim of this study was to investigate the effect of co-transplanting sciatic nerve Fbs (SN-Fbs) and sciatic nerve SCs (SN-SCs) on nerve regeneration. We developed a 5 mm nerve-defect model in mice using a polyurethane (PUR) catheter and then injected one of four different mixtures of cells into the catheters to form the following four groups: pure Matrigel (Control group), SN-Fbs alone (SN-Fb group), SN-Fbs combined with SN-SCs at a ratio of 1:2 (Fb&SC group) and SN-SCs alone (SN-SC group). Histological and functional analyses were performed 3 months later. The results indicated that in vitro, the expression levels of NGF, BDNF and GDNF were significantly higher, and in vivo, a more moderate amount of extracellular matrix was produced in the Fb&SC group than in the SN-SC group. Compared to the other groups, co-transplanting SN-Fbs with SCs at a 1:2 ratio had significantly positive effects on nerve regeneration and functional recovery.

A novel method for obtaining highly enriched Schwann cell populations from mature monkey nerves based on in vitro pre­degeneration.

Schwann cells (SCs) are indispensable for cell therapy and tissue engineering of the peripheral nervous system. Easy access to activated, highly proliferative SCs is necessary for clinical applications. The present study developed a fast, efficient method for obtaining highly purified SCs from the peripheral nerve of a mature Rhesus monkey. The common peroneal nerves of 4­year­old Rhesus monkeys were harvested and subjected to in vitro pre­degeneration in a modified SC culture medium (SCCM). The nerve pieces were subsequently treated enzymatically to dissociate the cells and then cultured for 2 days in SCCM. Cultured cells were treated with purification medium containing Ara­C to assist in restricting the overgrowth of fibroblast­like cells, for 24 h. After another 24­h cultivation period, the cells were subsequently treated with a multiplex collagenase, which enabled SC detachment over fibroblast detachment, and thereby facilitated SC isolation. Finally, SCs were cultured in SCCM. The cell yield was determined by cell counting following enzyme digestion and SC purity was determined from the percentage of SCs with respect to the total number of cells. Following purification, 96.3±3.9% of cells were identified as SCs. In vitro pre­degeneration in the presence of basic­fibroblast growth factor, heregulin ß1 and forskolin maximized the purity and yield of SCs that could be obtained from monkey peroneal nerves. The present study identified a novel technique that can efficiently isolate and purify SCs from mature monkey nerves based on in vitro pre­degeneration.

Fat tissue, a potential Schwann cell reservoir: isolation and identification of adipose-derived Schwann cells.

Schwann cells can be used to promote peripheral nerve repair. However, it is challenging to obtain abundant autologous Schwann cells without sacrificing nerve integrity. In this study, we isolated Schwann cells from murine inguinal adipose tissue and identified the cell phenotype and function in vivo and in vitro. Through H&E and immunofluorescence staining, we detected tiny nerve fibers and Schwann cells in adipose tissue. We evaluated the phenotype of spindle-shaped cells (Schwann cell-like cells, SCLCs) isolated from adipose tissue using immunofluorescence staining and real-time RT-PCR. The results showed that SCLCs expressed specific Schwann cell markers. Analysis of conditioned SCLC culture media showed that, similar to Schwann cells isolated from sciatic nerves, SCLCs secreted NGF and BDNF. SCLCs were harvested from CAG-EGFP transgenic mice and combined with silicone nerve conduits to repair sciatic nerve defects in wild-type mice. Six months post-surgery, we found EGFP-positive SCLCs forming myelin sheaths in the same way as sciatic nerve-derived Schwann cells. This research indicates the existence of Schwann cells in adipose tissue and identifies the spindle-shaped cells isolated from adipose tissue as Schwann cells using in vitro and in vivo evaluations. Thus, SCLCs might be promising seed cells for peripheral nerve tissue engineering.

Directly reprogramming fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by defined factors.

The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types represents a great potential technology for regenerative medicine. In the present study, the potential of key developmental adipogenic, neurogenic and hepatogenic regulators to reprogram human fibroblasts into adipocytes, neurocytes and hepatocytes was investigated. The results demonstrated that direct reprogramming of octamer-binding transcription factor 4 (Oct4) and CCAAT-enhancer-binding protein (C/EBP)ß activated C/EBPα and peroxisome proliferator-activated receptor-γ expression, inducing the conversion of fibroblasts into adipocytes. Similarly, direct reprogramming of the transcription factors sex determining region-box 2, trans-acting T-cell specific transcription factor (GATA-3) and neurogenic differentiation 1 in fibroblasts may induce neurogenic differentiation through hemagglutinating virus of Japan envelope (HVJ-E) transfection. Moreover, hepatogenic differentiation was induced by combining the direct reprogramming of Oct4, GATA-3, hepatocyte nuclear factor 1 homeobox α and forkhead box protein A2 in fibroblasts. These results demonstrate that specific transcription factors and reprogramming factors are able to directly reprogram fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by HVJ-E transfection.