Regarded as the most promising treatment modality for retinal degenerative diseases, retinal pigment epithelium cell replacement therapy holds significant potential. Common retinal degenerative ...diseases, including Age-related Macular Degeneration, are frequently characterized by damage to the unit comprising photoreceptors, retinal pigment epithelium, and Bruch's membrane. The selection of appropriate tissue engineering materials, in conjunction with retinal pigment epithelial cells, for graft preparation, can offer an effective treatment for retinal degenerative diseases. This article presents an overview of the research conducted on retinal pigment epithelial cell tissue engineering, outlining the challenges and future prospects.
The mammalian olfactory epithelium (OE) has a unique stem cell or progenitor niche, which is responsible for the constant peripheral neurogenesis throughout the lifespan of the animal. However, ...neither the signals that regulate the behavior of these cells nor the lineage properties of the OE stem cells are well understood. Multiple Wnt signaling components exhibit dynamic expression patterns in the developing OE. We generated Wnt signaling reporter TOPeGFP transgenic mice and found TOPeGFP activation predominantly in proliferating Sox2(+) OE basal cells during early postnatal development. FACS-isolated TOPeGFP(+) OE basal cells are required, but are not sufficient, for formation of spheres. Wnt3a significantly promotes the proliferation of the Sox2(+) OE sphere cells. Wnt-stimulated OE sphere cells maintain their multipotency and can differentiate into most types of neuronal and non-neuronal epithelial cells. Also, Wnt activators shift the production of differentiated cells toward olfactory sensory neurons. Moreover, TOPeGFP(+) cells are robustly increased in the adult OE after injury. In vivo administration of Wnt modulators significantly alters the regeneration potential. This study demonstrates the role of the canonical Wnt signaling pathway in the regulation of OE stem cells or progenitors during development and regeneration.
...antigen-independent homeostasis of T cells is vital for sustaining long-lived T cell-mediated immunity, and excessive IS may increase the risk of opportunistic infections and malignancies. ...IS ...therapy for LTx patients should be tailored to the immune status of the individual patient. Complete blood count data showed that patients with post-LTx BC had a decreased absolute number of white blood cells and neutrophils, with a slightly increased proportion of lymphocytes, but the absolute count of lymphocytes was similar. Three patients with infections in the BC group (18.75%) had C-reactive protein levels >10 mg/L on the day for T cell analysis.
For 70 years, α-amanitin, the most cytotoxic peptide in its class, has been without a synthetic rival; through synthesis, we address the structure–activity relationships to inform the design of new ...amatoxins and disclose analogues that are more cytotoxic than the natural product when evaluated on CHO, HEK293, and HeLa cells, whereas on liver-derived HepG2 cells, the same toxins show diminished cytotoxicity.
Ischemia not only leads to tissue damage, but also induces seizures, which in turn worsens the outcome of ischemia. Recent studies have revealed the impaired homeostatic functions of reactive ...astrocytes, which were thought to facilitate the development of seizures. However, how this phenotype of reactive astrocytes is regulated remains unclear. Here, using pentylenetetrazole (PTZ)‐kindling model, we investigated the roles of reactive astrocytes and their intracellular Wnt/β‐catenin signaling in the ischemia‐increased seizure susceptibility. Our data showed that somatosensory cortical ischemia significantly increased the susceptibility to PTZ‐induced seizure. Genetic ablation of Nestin‐positive reactive astrocytes significantly decreased the incidence and severity of seizures. By using a Wnt signaling reporter mice line Topgal mice, we found that Wnt/β‐catenin signaling was upregulated in reactive astrocytes after ischemia. Depletion of β‐catenin in reactive astrocytes significantly decreased the susceptibility of seizures and the expression of c‐Fos induced by PTZ in the ischemic cortex. Overexpression of β‐catenin in reactive astrocytes, in contrast, significantly increased seizure susceptibility and the expression of c‐Fos. Furthermore, the expression of aquaporin‐4 (AQP‐4) and inwardly rectifying K+ channel 4.1 (Kir4.1), two molecules reportedly associated with seizure development, was oppositely affected in reactive astrocytes with β‐catenin depletion or overexpression. Taken together, these data indicated that astrocytic Wnt/β‐catenin signaling accounts, at least partially, for the ischemia‐increased seizure susceptibility. Inhibiting Wnt/β‐catenin signaling may be utilized in the future for preventing postischemic seizures. GLIA 2016;64:1083–1091
Main Points
Reactive astrocytes contribute to the ischemia‐enhanced seizure susceptibility.
Wnt/β‐catenin signaling is activated in reactive astrocytes.
Wnt/β‐catenin signaling accounts for the seizure‐facilitating effects of reactive astrocytes.
Background
With increasing detection of small renal masses and accumulating evidence that nephron sparing surgery (NSS) could achieve oncological equivalence and functional superiority compared with ...radical nephrectomy (RN), NSS has become first‐line therapy for some patients with localized renal masses.
Objective
This study aims to review the publications in the kidney neoplasm and NSS field, exploring the research hotspots.
Method
Kidney neoplasm and NSS related publications before July 3th 2023 were obtained from the Web of Science Core Collection database. We then used bibliometric analysis to conduct performance analysis, citation analysis and co‐citation network of publications, together with keyword co‐occurrence analysis.
Results
Seven thousand five hundred and sixty‐four documents were finally retrieved, and the annual publications increased exponentially. The most productive authors were “KAOUK JH” and “GILL IS”, while USA, and 12 American affiliations such as CLEVELAND CLINIC FOUNDATION and MAYO CLINIC were far leading in this field. Journal of Urology and European Urology were journals with the highest citations and h‐index.
Discussion
Through literature reviewing plus co‐occurrence and clustering analysis, the therapeutic effects of partial nephrectomy (PN) versus RN on patients with localized renal cell carcinoma, different operative approaches of PN, and conservative NSS methods were deemed as the most focused topics.
Conclusion
Three aspects were the most important hotspots in this field. Firstly, how to provide the optimal management choices for different patients. Secondly, therapeutic effects of different management options and surgical techniques needed more prospective and randomized studies. Finally, more novel technologies and surgical techniques were required.
Red cluster mainly discussed the therapeutic effects of PN versus RN on patients with localized RCC. In blue cluster, more conservative NSS methods including TA and AS were mainly focused. Last but not the least, we discussed different operative approaches of PN in the green cluster.
In mammals, microRNAs (miRNAs) play key roles in multiple biological processes by regulating the expression of target genes. Studies have found that the levels of miR-370-5p expression differ ...significantly in the skins of sheep with different hair colors; however, its function remains unclear. In this study, we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation (P<0.01), tyrosinase activity (P=0.001) and significantly reduced (P<0.001) melanin production. Functional prediction revealed that the 3´-untranslated region (UTR) of MAP3K8 has a putative miR-370-5p binding site, and the interaction between these two molecules was confirmed using luciferase reporter assays. In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes. The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits (P<0.01) MAP3K8 expression via direct targeting of its 3´ UTR. Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition (P<0.01) of melanocyte proliferation and significant reduction (P<0.001) in melanin production, which is consistent with our observations for miR-370-5p. Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA (containing sites for the targeted binding to miR-370-5p) was significantly rescued (P≤0.001), which subsequently promoted significant increases in cell proliferation (P<0.001) and melanin production (P<0.01). Collectively, these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.
The precise prediction of end-point carbon content in liquid steel plays a critical role in increasing productivity as well as energy efficiency that can be achieved in the basic oxygen furnace (BOF) ...steelmaking process. Due to numerous and diversity of the studies on BOF end-point carbon prediction, it seems necessary to provide a comprehensive literature review on state-of-the-art developments in end-point carbon prediction for BOF steelmaking. This paper presents the characteristics of different end-point carbon prediction models. The end-point carbon prediction for BOF steelmaking has initially relied on the experience and skill of the operators. With the development of information technology and auto-detection methods, BOF end-point carbon prediction mainly has gone through three stages, such as static prediction, dynamic prediction, and intelligent prediction. Future contributions to the development and application of intelligent end-point carbon prediction in BOF steelmaking are still arduous tasks. However, it is envisaged that the intelligent end-point carbon prediction will witness more frequent applications and greatly improve the high-quality, high-efficiency, and stable production for BOF steelmaking in the future.
Lipophilic shellfish toxins (LSTs) can cause human illness and therefore represent a serious threat to public health. Shellfish are the main dietary source of LSTs, but very few studies have ...appraised dietary exposure to LSTs through shellfish consumption in China. We measured levels of multiple LSTs in shellfish samples sold in the principal wholesale seafood market in the southern coastal city of Shenzhen, and we estimated the potential for acute and chronic LST exposure of the Shenzhen population via ingestion of shellfish. LST contamination data were obtained from a total of 14 species of 188 commercial samples. Eleven individual LSTs, namely okadaic acid (OA), dinophysis toxin-1 and −2 (DTX1 and DTX2), pectenotoxin-2 (PTX2), yessotoxin and homo yessotoxin (YTX and hYTX), azaspiracid-1, −2 and −3 (AZA1, AZA2, AZA3), spirolides (SPXs), and gymnodimine (GYM), were determined using liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS/MS). More than two thirds of samples showed undetectable LSTs, while the detection rates (the proportion of samples with detectable LSTs) of individual LSTs ranged from 0% to 45.7%. Most shellfish samples had lower levels of LST contamination than the corresponding limits of detection (LODs), while some samples had levels of hYTX and GYM that exceeded the limits of quantification (LOQs). Overall, levels of LSTs in the 188 samples were below the regulatory limits set by most countries. Acute and chronic exposures of LST were estimated by a point-estimate modeling method that combined sample contamination data with consumption data from dietary survey of Shenzhen residents and consumption figures proposed by EFSA, the European Food Safety Authority. Seasonal variations in LST concentrations were noted in some instances. Overall, the estimated acute exposure to LSTs based on consumption of large-size shellfish portions and the maximum LSTs contamination level were below the provisional acute reference doses (ARfDs) proposed by the EFSA. Chronic exposure estimates based on mean and 99th percentile consumption of shellfish by Shenzhen residents and mean LSTs contamination levels in the collected samples were from 2452 to 74 times lower than those associated with estimated acute exposure levels.
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•Lipophilic shellfish toxins (LSTs) that contaminate shellfish consumed in Shenzhen, China, were assessed for the first time.•11 individual LST concentration data of LSTs in commercial shellfish samples collected commercially across all seasons was measured for assessment.•The estimated acute exposure levels were below the ARfDs proposed by the European Food Safety Authority.•Data generated in this study provide a scientific basis for chronic risk assessment of LSTs.
Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (
-
), along ...with seven known analogs (
-
), were isolated from the fermentation broth of the mangrove strain
GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against
with minimum inhibitory concentration (MIC) values being in the range of 2-128 μg/mL except compound
. This is the first report of polyene derivatives produced by
as bioactive compounds against
.
. In vitro studies showed that compound
exerted a significantly stronger antifungal activity against
.
than other new compounds, and the antifungal mechanism of compound
may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound
preventing and controlling talaromycosis.
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