Serum tRF-33-RZYQHQ9M739P0J as a novel biomarker for auxiliary diagnosis and disease course monitoring of hepatocellular carcinoma.

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis. Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction. Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC. Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

Non-invasive diagnosis of bacterial and non-bacterial inflammations using a dual-enzyme-responsive fluorescent indicator.

Bacterial infections, as the second leading cause of global death, are commonly treated with antibiotics. However, the improper use of antibiotics contributes to the development of bacterial resistance. Therefore, the accurate differentiation between bacterial and non-bacterial inflammations is of utmost importance in the judicious administration of clinical antibiotics and the prevention of bacterial resistance. However, as of now, no fluorescent probes have yet been designed for the relevant assessments. To this end, the present study reports the development of a novel fluorescence probe (CyQ) that exhibits dual-enzyme responsiveness. The designed probe demonstrated excellent sensitivity in detecting NTR and NAD(P)H, which served as critical indicators for bacterial and non-bacterial inflammations. The utilization of CyQ enabled the efficient detection of NTR and NAD(P)H in distinct channels, exhibiting impressive detection limits of 0.26 µg mL-1 for NTR and 5.54 µM for NAD(P)H, respectively. Experimental trials conducted on living cells demonstrated CyQ's ability to differentiate the variations in NTR and NAD(P)H levels between A. baumannii, S. aureus, E. faecium, and P. aeruginosa-infected as well as LPS-stimulated HUVEC cells. Furthermore, in vivo zebrafish experiments demonstrated the efficacy of CyQ in accurately discerning variations in NTR and NAD(P)H levels resulting from bacterial infection or LPS stimulation, thereby facilitating non-invasive detection of both bacterial and non-bacterial inflammations. The outstanding discriminatory ability of CyQ between bacterial and non-bacterial inflammation positions it as a promising clinical diagnostic tool for acute inflammations.

Oat ß-glucan repairs the epidermal barrier by upregulating the levels of epidermal differentiation, cell-cell junctions and lipids via Dectin-1.

BACKGROUND AND PURPOSE: Oat ß-glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin-1 is one of the receptors of ß-glucan and many biological functions of ß-glucan are mediated by Dectin-1. Dectin-1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat ß-glucan and Dectin-1 in epidermal barrier repair. EXPERIMENTAL APPROACH: To investigate the role of Dectin-1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell-cell junctions and lipid content were compared between WT and Dectin-1-/- mice. Further, the effect of oat ß-glucan on the disruption of the epidermal barrier was also compared between WT and Dectin-1-/- mice. KEY RESULTS: Dectin-1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell-cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat ß-glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell-cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin-1. Oat ß-glucan could promote CaS receptor expression and activate the PPAR-γ signalling pathway via Dectin-1. CONCLUSION AND IMPLICATIONS: Oat ß-glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell-cell junctions and lipid synthesis through Dectin-1. Dectin-1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin-1 may be a potential target in epidermal barrier repair.

Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape.

Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of ß-catenin into the nucleus by activating Wnt/ß-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited theinfiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases.

Establishment of Complete Capillary Blood Counts Reference Intervals for Young Children in Local Area, China.

BACKGROUND: Blood count reference intervals are important to diagnose diseases and assess overall health, especially for young children. Although, in 2021, the National Health Commission of the People's Republic of China issued "Reference intervals of blood cell analysis for children (WS/T 779-2021)", these RIs may not suitable for small children all over the country due to racial, lifestyle, and geographical differences. The aim of this study was to establish and validate locally determined hematological reference intervals among young children in Nantong district and compare them with WS/T 779-2021 and American data. METHODS: The reference sample consisted of 4,758 apparently healthy small children aged from age 28 days to 3 years according to the EP28-A3c guideline issued by the Clinical and Laboratory Standards Institute (CLSI). Capillary blood samples collected in K2-EDTA anticoagulant tubes analyzed by standard procedures. Statistical analysis was based on the guidelines of the CLSI. RESULTS: Pediatric reference intervals for 18 capillary complete blood count (CCBC) parameters were established for young children. WBC and differentials did not differ by gender in the combined analysis of all data, but showed some variations among different age groups, especially for NE and LYM. RIs of RBC value, MCV, and MCH were established, especially with regard to the difference among different age and gender groups. An overall increasing trend of PLT value was observed in children with no obvious difference between boys and girls. Further validation with 1,136 healthy subjects demonstrated that the verified proportions of our study were within 90.11% - 100%. RIs determined in the present study were more concentrated than WS/T 779-2021, with slight differences in the upper and bottom boundaries. CONCLUSIONS: Establishing appropriate region-specific reference intervals for pediatrics is essential. This study offers local reference intervals of CCBC values for young children and could be used as a benchmark for similar populations in the Yangtze River Delta economic region.

SLC7A11 promotes the progression of gastric cancer and regulates ferroptosis through PI3K/AKT pathway.

OBJECTIVE: Ferroptosis is a form of regulated cell death that occurs depending on iron and reactive oxygen species (ROS), but the underlying molecular mechanisms remain poorly understood. The aim of our study was to investigate the role of solute carrier family 7 member 11(SLC7A11) in the progression of gastric cancer (GC) and its molecular mechanism. METHOD: The expression of SLC7A11 in GC was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blot. SLC7A11 interference and overexpression vector was constructed in vitro, transfected into GC cells, and the high efficiency plasmid vector fragment was screened.CCK-8 assay was used to detect the effect of cell proliferation. The migration ability of cells was detected by transwell assay. The mitochondrial structure was observed by transmission electron microscopy.CCK-8 assay was also used to detect the effect of SLC7A11 on the growth inhibition rate of ferroptosis in GC cells. The level of malondialdehyde (MDA), the ultimate product of lipid peroxidation, was detected by micro-method. The effect of SLC7A11 on PI3K/AKT signaling pathway was detected by Western blot. RESULTS: SLC7A11 was significantly overexpressed in GC tissues than that in adjacent tissues. Knockdown of SLC7A11 inhibits cell proliferation, cell migration and invasion of GC, and increases the sensitivity of ferroptosis via moderating ROS and lipid peroxidation. Besides, overexpression of the SLC7A11 in GC cells reverses erastin-induced ferroptosis partially. Mechanistically, we reveal that suppression of SCL7A11 leads to inactivity of PI3K/AKT signaling pathway and further enhancing ferroptosis related lipid peroxidation, and thereby inhibiting GC progression. CONCLUSION: SLC7A11 plays an oncogene role in malignant progression of GC. SLC7A11 reversely regulates ferroptosis of GC cells by activating PI3K/AKT signaling pathway. Silencing SLC7A11 expression can inhibit the progression of GC.

Overexpression of ferroptosis-related genes FSP1 and CISD1 is related to prognosis and tumor immune infiltration in gastric cancer.

PURPOSE: Gastric cancer (GC) is one of the highest incidence rate cancers worldwide and the search for new biomarkers remains urgent due to its relatively poor prognosis and limited treatment methods. Ferroptosis suppressor protein 1 (FSP1) and iron sulfur domain 1 (CISD1) promoted malignant tumor progression as ferroptosis suppressors in a variety of tumors, but their study in GC remains to be explored. METHODS: In our study, FSP1 and CISD1 expression were predicted through different databases and confirmed by qRT-PCR, immunohistochemistry and western blotting. Enrichment analyses were exploited to explore the potential functions of FSP1 and CISD1. Finally, their relationship with immune infiltration was determined by Tumor Immune Estimation Resource and ssGSEA algorithm. RESULTS: The expression of FSP1 and CISD1 was higher in GC tissues. Their strongly positive immunostaining was associated with increased tumor size, degree of differentiation, depth of invasion and lymph node metastasis in GC patients. Up-regulated FSP1 and CISD1 predicted poorer overall survival of patients with GC. Furthermore, FSP1 and CISD1 as ferroptosis inhibitors were predicted to be involved in GC immune cell infiltration. CONCLUSIONS: Our study suggested that FSP1 and CISD1 acted as biomarkers of poor prognosis and promising immunotherapeutic targets for GC.

Protective effect of Saussurea involucrata polysaccharide against skin dryness induced by ultraviolet radiation.

Background: Exposure to ultraviolet B (UVB) radiation can damage the epidermis barrier function and eventually result in skin dryness. At present, little work is being devoted to skin dryness. Searching for active ingredients that can protect the skin against UVB-induced dryness will have scientific significance. Methods: Saussurea involucrata polysaccharide (SIP) has been shown to have significant antioxidant and anti-photodamage effects on the skin following UVB irradiation. To evaluate the effect of SIP on UVB-induced skin dryness ex vivo, SIP-containing hydrogel was applied in a mouse model following exposure to UVB and the levels of histopathological changes, DNA damage, inflammation, keratinocyte differentiation, lipid content were then evaluated. The underlying mechanisms of SIP to protect the cells against UVB induced-dryness were determined in HaCaT cells. Results: SIP was found to lower UVB-induced oxidative stress and DNA damage while increasing keratinocyte differentiation and lipid production. Western blot analysis of UVB-irradiated skin tissue revealed a significant increase in peroxisome proliferator-activated receptor-α (PPAR-α) levels, indicating that the underlying mechanism may be related to PPAR-α signaling pathway activation. Conclusions: By activating the PPAR-α pathway, SIP could alleviate UVB-induced oxidative stress and inhibit the inflammatory response, regulate proliferation and differentiation of keratinocytes, and mitigate lipid synthesis disorder. These findings could provide candidate active ingredients with relatively clear mechanistic actions for the development of skin sunscreen moisturizers.

Cryptotanshinone protects skin cells from ultraviolet radiation-induced photoaging via its antioxidant effect and by reducing mitochondrial dysfunction and inhibiting apoptosis.

The integrity of skin tissue structure and function plays an important role in maintaining skin rejuvenation. Ultraviolet (UV) radiation is the main environmental factor that causes skin aging through photodamage of the skin tissue. Cryptotanshinone (CTS), an active ingredient mianly derived from the Salvia plants of Lamiaceae, has many pharmacological effects, such as anti-inflammatory, antioxidant, and anti-tumor effects. In this study, we showed that CTS could ameliorate the photodamage induced by UV radiation in epidermal keratinocytes (HaCaT) and dermal fibroblasts (HFF-1) when applied to the cells before exposure to the radiation, effectively delaying the aging of the cells. CTS exerted its antiaging effect by reducing the level of reactive oxygen species (ROS) in the cells, attenuating DNA damage, activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and reduced mitochondrial dysfunction as well as inhibiting apoptosis. Further, CTS could promote mitochondrial biosynthesis in skin cells by activating the AMP-activated protein kinase (AMPK)/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) signaling pathway. These findings demonstrated the protective effects of CTS against UV radiation-induced skin photoaging and provided a theoretical and experimental basis for the application of CTS as an anti-photodamage and anti-aging agent for the skin.

Cucurbitacin promotes hair growth in mice by inhibiting the expression of fibroblast growth factor 18.

Background: The inhibition of fibroblast growth factor 18 (FGF18) promotes the transition of hair follicles (HFs) from the telogen phase to the anagen phase. Cucurbitacin has been shown to have a good effect in promoting hair cell growth. This study explored the potential effect of cucurbitacin on hair growth and its effect on FGF18 expression in mice. Methods: Male C57BL/6J mice were randomly divided into the following two groups: (I) the vehicle group; and (II) the cucurbitacin group. Matrix cream and cucurbitacin cream were applied to the depilated skin on the back of the vehicle group mice and the cucurbitacin group mice, respectively. On days 3, 6, 9, 12, 15, and 18, the hair growth in the depilated dorsal skin of the mice was recorded with a digital camera and a HF detector, and the HF cycle status of the mice was observed by hematoxylin and eosin (H&E) staining. In addition, the level of FGF18 messenger ribonucleic acid (mRNA) in the dorsal skin was measured on days 15 and 18 by quantitative real-time polymerase chain reaction (qRT-PCR), while the level of FGF18 protein was measured by western blot and immunofluorescence staining. Results: The dorsal skin to which the cucurbitacin cream was applied began to darken on day 6 and grew hairs on day 9, which was 3 days earlier than the dorsal skin to which the matrix cream was applied. The H&E staining revealed a transition from the telogen phase to the anagen phase 3 days earlier for the cucurbitacin cream-treated skin than the matrix cream-treated skin. In addition, the skin treated with cucurbitacin cream also showed a significant decrease in FGF18 mRNA as seen by qRT-PCR, and reduced FGF18 protein levels as detected by western blot and immunofluorescence staining compared to the skin treated with matrix cream only. Conclusions: Cucurbitacin significantly reduced the levels of FGF18 mRNA and protein in the dorsal skin of mice to accelerate the HFs to enter the anagen phase earlier, thereby promoting the regeneration of hair. Thus, cucurbitacin can be considered a new and valuable agent for the development of anti-hair loss products.

Expression Profile and Bioinformatics Analysis of Circular RNAs in Patients with Vitiligo.

Purpose: Circular RNAs (circRNAs) are abundant, stable, and evolutionarily conserved noncoding RNAs with impacts on cell proliferation, differentiation, invasion, apoptosis, and immunity by acting as an miRNA sponge. This study aimed to investigate the expression of circRNAs in vitiligo and analyze the differentially expressed circRNAs (DEcircRNAs) bioinformatically. Patients and Methods: Biopsies of five lesional and five nonlesional skins of patients with vitiligo and five healthy skins (control) were harvested in this study. The expression profiles of circRNAs and DEcircRNAs were determined by microarray analysis and qRT-PCR. Bioinformatics analysis was used to predict target genes of DEcircRNAs binding to miRNAs and their underlying functions. Meanwhile, a competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Results: A total of 817 and 508 DEcircRNAs were identified in lesional and nonlesional skins of patients with vitiligo, respectively. The results of hsa_circRNA_000957 and hsa_circRNA_101798 validation were consistent with our microarray analysis. Furthermore, 32 miRNA response elements (MREs) and related target genes of DEcircRNAs were identified, whose main functions were involved in the pathogenesis of vitiligo. Hsa_circRNA_000957 and hsa_circRNA_101798 might be candidate biomarkers for vitiligo. Conclusion: This study provides scientific clues for understanding the mechanism of vitiligo.

Precisely controlled and deeply penetrated micro-nano hybrid multifunctional motors with enhanced antibacterial activity against refractory biofilm infections.

The biofilm resistance of microorganisms has severe economic and environmental implications, especially the contamination of facilities associated with human life, including medical implants, air-conditioning systems, water supply systems, and food-processing equipment, resulting in the prevalence of infectious diseases. Once bacteria form biofilms, their antibiotic resistance can increase by 10-1,000-fold, posing a great challenge to the treatment of related diseases. In order to overcome the contamination of bacterial biofilm, destroying the biofilm's matrix so as to solve the penetration depth dilemma of antibacterial agents is the most effective way. Here, a magnetically controlled multifunctional micromotor was developed by using H2O2 as the fuel and MnO2 as the catalyst to treat bacterial biofilm infection. In the presence of H2O2, the as-prepared motors could be self-propelled by the generated oxygen microbubbles. Thereby, the remotely controlled motors could drill into the EPS of biofilm and disrupt them completely with the help of bubbles. Finally, the generated highly toxic •OH could efficiently kill the unprotected bacteria. This strategy combined the mechanical damage, highly toxic •OH, and precise magnetic guidance in one system, which could effectively eliminate biologically infectious fouling in microchannels within 10 min, possessing a wide range of practical application prospects especially in large scale and complex infection sites.

Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer.

Most small non-coding RNAs (sncRNAs) with regulatory functions are encoded by majority sequences in the human genome, and the emergence of high-throughput sequencing technology has greatly expanded our understanding of sncRNAs. sncRNAs are composed of a variety of RNAs, including tRNA-derived small RNA (tsRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNA), etc. While for some, sncRNAs' implication in several pathologies is now well established, the potential involvement of tsRNA, snoRNA, snRNA and piRNA in human diseases is only beginning to emerge. Recently, accumulating pieces of evidence demonstrate that tsRNA, snoRNA, snRNA and piRNA play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer. Abnormal expression of tsRNA, snoRNA, snRNA and piRNA participates in the occurrence and development of tumours through different mechanisms, such as transcriptional inhibition and post-transcriptional regulation. In this review, we describe the research progress in the classification, biogenesis and biological function of tsRNA, snoRNA, snRNA and piRNA. Moreover, we emphasised their dysregulation and mechanism of action in cancer and discussed their potential as diagnostic and prognostic biomarkers or therapeutic targets.

Diagnostic Value of Circular RNA hsa_circ_0002874 Expression in Peripheral Blood of Patients with Gastric Cancer.

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524-9.048), 1.261 (IQR, 0.817-2.000), and 1.00 (IQR, 0.726-1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P < .001) and lymph node metastasis (U = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC.

Protective effects of fucoidan purified from Undaria pinnatifida against UV-irradiated skin photoaging.

BACKGROUND: Exposure to ultraviolet (UV) radiation (UVB and UVA) is the most well-known extrinsic factor that induces skin aging. Fucoidan has been shown to possess antiphotoaging effects against UV irradiation and can be used as an ingredient in the pharmaceutical industry. The present study evaluated the photoprotective effect of fucoidan purified from Undaria pinnatifida (UPF) on UV-induced skin photoaging and explored its potential molecular mechanism. METHODS: To evaluate the effect of UPF on UV-induced skin aging, HaCaT cells and HFF-1 cells were pretreated with or without UPF and then exposed to UVB and UVA radiation, respectively, and the levels of cellular senescence, reactive oxygen species (ROS) production and mitochondrial dysfunction were evaluated. The mitochondrial ROS (mROS) was stained through MitoSOX, and the confocal microscope was used to capture the images. For further exploration of AMPK/SIRT-1/PGC-1α signaling, western blot was employed. RESULTS: The results demonstrated that pretreatment of HaCaT and HFF-1 cells with UPF ameliorated cellular senescence, ROS and mROS overproduction, and mitochondrial dysfunction caused by UV exposure. This research also revealed that UPF could activate the AMPK/SIRT-1/PGC-1α signaling pathway to promote mitochondrial biogenesis. CONCLUSIONS: UPF can ameliorate UV-induced skin photoaging through inhibition of ROS production via the alleviation of mitochondrial dysfunction by regulating the SIRT-1/PGC-1α signaling pathway.

Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice.

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

A method for the expression of fibroblast growth factor 14 and assessment of its neuroprotective effect in an Alzheimer's disease model.

BACKGROUND: Fibroblast growth factor (FGF) 14 is a member of the FGF family that is mainly expressed in the central nervous system. FGF14 has a close association with the occurrence of neurodegenerative conditions; however, its significance in Alzheimer's disease (AD) has yet to be evaluated. Therefore, we sought to obtain a large amount of exogenous FGF14 protein and explore its effect in a cellular model of AD. METHODS: FGF14 protein was expressed in an Escherichia coli system using gene recombination technology. Purified protein was obtained through washing and renaturation of inclusion bodies combined with nickel column affinity chromatography. The AD model was established via Aß25-35-induced injury in PC12 cells. Changes in the levels of lactate dehydrogenase and malondialdehyde were detected, and the neuroprotective effect of recombinant human FGF14 (rhFGF14) was evaluated through double-fluorescence staining and flow cytometry apoptosis detection. For further exploration of rhFGF14-mediated regulation of mitogen-activated protein kinase (MAPK) signaling, western blot was employed. RESULTS: We successfully induced large amounts of insoluble rhFGF14. Following solubilization and refolding of the rhFGF14 from inclusion bodies, high purity rhFGF14 was purified by Nickel affinity column chromatography. The results showed that rhFGF14 alleviated Aß25-3-induced PC12 cell injury by inhibiting the phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, thus suppressing the MAPK signaling pathway. CONCLUSIONS: FGF14 performed a neuroprotective role in our in vitro AD model via its inhibition of MAPK signaling, highlighting its potential as a therapeutic drug for neurodegenerative conditions.

Oat ß-glucan ameliorates epidermal barrier disruption by upregulating the expression of CaSR through dectin-1-mediated ERK and p38 signaling pathways.

The integrity of the epidermal barrier and the maintenance of barrier homeostasis depend on the dynamic balance between the proliferation and differentiation of keratinocytes. Calcium (Ca2+) plays a crucial role in maintaining a balance of these two processes as well as in the formation of an epidermal permeability barrier. In this study, we showed that topical application of oat ß-glucan (OG) could ameliorate epidermal hyperplasia and accelerate the recovery of the epidermal barrier by promoting epidermal differentiation. Mechanistic studies revealed a positive interaction between OG and the dectin-1 receptor, and this interaction could lead to an upregulated expression of the calcium-sensing receptor (CaSR) via activation of the downstream ERK and p38 pathways. This consequently increased the sensitivity of keratinocytes to extracellular Ca2+ under the condition of calcium loss following the disruption of the epidermal barrier, resulting in the maintenance of normal keratinocyte differentiation in the epidermis, and ultimately promoting the recovery of the epidermal barrier. These findings clearly demonstrated the healing effect of OG on a physically damaged epidermal barrier. Thus, OG could be considered a valuable component in the development of skin repair agents.