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.

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.

Intracerebral hemorrhage alters circular RNA expression profiles in the rat brain.

Circular RNAs (circRNAs), formed from pre-messenger RNAs by back-splicing, are a novel class of evolutionarily-conserved endogenous non-coding RNAs. While circRNAs are involved in various diseases, the role of circRNAs in intracerebral hemorrhage (ICH) remains unknown. In the present study, we performed high-throughput sequencing to profile the expression of circRNAs in the rat brain at 24 and 48 hours after ICH onset, and utilized bioinformatics methods to make predictions about the function of dysregulated circRNAs. Compared with the sham group, 346 and 389 circRNAs changed significantly (|log2 (fold change)| > 1 and P < 0.05) at 24 and 48 hours after ICH, respectively. Bioinformatics analyses indicated that parent genes of dysregulated circRNAs were involved in biological processes, cellular component, and molecular function following ICH, and that they were enriched in the dopaminergic synapses, glutamatergic synapses, endocytosis, regulation of actin cytoskeleton, the mitogen-activated protein kinase signaling pathway, and the retrograde endocannabinoid signaling pathway. Enrichment analyses of target mRNAs showed that these mRNAs were enriched in synaptic plasticity, ion channel activity, and pathways including the phospholipase D signaling and the cGMP-PKG signaling. Our study indicates that the expression profile of circRNAs changes significantly after ICH in rat brains, and suggests that circRNAs may be crucial for the pathophysiological process following ICH.

Altered circular RNA expression profiles in the non-ischemic thalamus in focal cortical infarction mice.

Focal cerebral infarction leads to secondary changes in non-ischemic areas remote from but connected to the infarct site. Circular RNAs (circRNAs) are involved in the pathophysiological processes of many diseases. However, the expression and roles of circRNAs in non-ischemic remote regions after ischemic stroke remain unknown. In this study, adult male C57BL/6J mice were subjected to permanent distal middle cerebral artery occlusion (MCAO) to establish focal cortical infarction. High-throughput sequencing was used to profile the circRNA expression in the mouse ipsilateral thalamus at 7 and 14 d after MCAO. Bioinformatics analyses were conducted to predict the function of the differential expressed circRNAs' host and target genes. Compared with sham group, a total of 2659 circRNAs were significantly altered in the ipsilateral thalamus at 7 or 14 d after MCAO in mice. Among them, 73 circRNAs were significantly altered at both two time points after stroke. GO and KEGG analyses indicated that circRNAs plays important roles in secondary thalamic neurodegeneration and remodeling after focal cortical infarction. This is the first study to profile the circRNA expression in non-ischemic region of ischemic stroke, suggesting that circRNAs may be therapeutic targets for reducing post-stroke secondary remote neurodegeneration.

Challenges in diagnosis of pulmonary mucoepidermoid carcinoma: A case report.

RATIONALE: Pulmonary mucoepidermoid carcinomas (PMECs) of the lung are rare malignant tumors. Despite progresses in examinations, the tumor represents a diagnostic challenge for pathologists and clinical physicians. Here, we present a patient who was eventually diagnosed with PMEC by the bronchoscopic examinations conducted three times. PATIENT CONCERNS: We present the case of a 41-year-old female who was initially diagnosed with pulmonary pleomorphic adenoma (PPA) with a 68 × 82 mm mass and nodules in her lung and eventually diagnosed with PMEC. DIAGNOSES: Based on histopathology, immunohistology, and imaging studies, the patient was diagnosed with PMEC (pT4N2M1). INTERVENTIONS: The patient received first-line systemic chemotherapy regime (gemcitabine combined with carboplatin). OUTCOMES: The patient received 2 cycles of chemotherapy. Based on the response evaluation criteria in solid tumor, she achieved partial response, and the mass was distinctly decreased from 68 × 22 mm to 41 × 17 mm. LESSONS: This case presents a rare PMEC overlapping with PPA, based on histological findings, suggesting that besides imaging studies and laboratory examinations, multiple biopsies and ThinPrep cytology tests are necessary to obtain an accurate diagnosis. The patient showed positive response to chemotherapy.

Efficacy and safety of PD1/PDL1 blockades versus docetaxel in patients with pretreated advanced non-small-cell lung cancer: a meta-analysis.

BACKGROUND: PD1/PDL1 blockade is a promising treatment for patients with non-small-cell lung cancer (NSCLC). Here, we employed meta-analysis to evaluate the efficacy and safety of PD1/PDL1 blockades for previously treated NSCLC patients. METHODS: Randomized clinical trials were retrieved by searching electronic databases. Data for HRs, 95% CIs for overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were extracted and pooled. RESULTS: A total of five randomized controlled trials including 2,910 patients were included in this meta-analysis. Pooled HRs (95% CI) were 0.71 (0.63-0.79, P<0.0001) for OS and 0.86 (0.73-1.02) for PFS. In the subgroup analysis, the pooled HR (95% CI) for PFS was 0.82 (0.75-0.91, P<0.0001) in patients with high PDL1 expression, but no significant difference was seen in patients with low expression (0.97 [0.76-1.24], P=0.82). The pooled RR for treatment-related AEs of all grades was 0.32 (0.27-0.38, P<0.00001) compared with the docetaxel arm, while that for grade 3-5 treatment-related AEs in the PD1/PDL1-blockade arm was 0.16 (0.10-0.27, P<0.00001). CONCLUSION: PD1/PDL1 blockades enhanced OS and PFS and led to lower risk of AEs in NSCLC patients. Smoking history and wild-type EGFR were associated with extended OS.

Intranasal administration of nerve growth factor promotes angiogenesis via activation of PI3K/Akt signaling following cerebral infarction in rats.

Angiogenesis plays a critical role in neural repair following ischemic stroke. Therapeutic angiogenesis contributes to neurological functional recovery after cerebral infarction. Nerve growth factor (NGF) has been reported as a neurotrophic factor. However, the angiogenic efficacy of NGF in cerebral ischemia remains unclear. In this study, we investigated the effect of NGF on angiogenesis in the ischemic penumbra and neurological outcome in a rat model of middle cerebral artery occlusion (MCAO). Our results demonstrate that the intranasal administration of NGF improves neurological outcome and reduces infarct volume on day 7 after MCAO in rats. Treatment with NGF promoted angiogenesis in the peri-infarct region, increased the serum levels of VEGF and SDF-1 protein, and elevated the number of circulating endothelial progenitor cells (EPCs) on day 4 after MCAO. In addition, NGF enhanced capillary-like tube formation of rat brain microvascular endothelial cells in vitro, further confirming its angiogenic effect. Furthermore, the neuroprotective and angiogenic effects of NGF can be significantly attenuated by the phosphatidylinositide 3-kinase (PI3K)/Akt pathway antagonist LY294002. Our results indicate that NGF-enhanced angiogenesis contributes to neurological functional recovery after ischemic stroke, which may occur partly via activation of the PI3K/Akt signaling pathway. This study provides novel experimental evidence for the angiogenic role of NGF in treating ischemic stroke.

Spontaneous spinal epidural hematoma mimicking transient ischemic attack: A case report.

RATIONALE: Spontaneous spinal epidural hematoma (SSEH) is a rare but highly disabling neurological emergency. The initial presentations are variable. Most patients of SSEH present with paraplegia or tetraplegia clinically, but recurrent hemiparesis with complete spontaneous recovery, mimicking transient ischemic attack (TIA), is a very rare initial presentation of SSEH. PATIENT CONCERNS: A 71-year-old female presented to the emergency department with 2 episodes of transient right hemiparesis in 5 hours. Two days later, above symptom reappeared and progressed to quadriplegia, dyspnea, and uroschesis quickly. The neurological examination showed tetraplegia and hypalgesia below the C2 level, but neither facial palsy nor aphasia was found. DIAGNOSIS: The patient was initially misdiagnosed as TIA and treated with antiplatelet therapy. But during the hospital day, the cervical magnetic resonance imaging showed a dorsal epidural hematoma extending from C2 to C6 level and she was diagnosed as SSEH. INTERVENTIONS: She underwent surgical decompression and hematoma removal 1 week later. OUTCOMES: One week after operation, the sensory deficit above C6 level improved, but there was no improvement in her muscle strength and dyspnea. Unfortunately, she died 1 month later. LESSONS: Our case highlights recurrent hemiparesis with complete spontaneous recovery mimicking TIA is a rare initial presentation of SSEH. It is important to perform careful clinical assessments and neuroimaging investigations for correct diagnosis. Neck pain and hemiparesis sparing cranial nerve are important signs for distinction of SSEH from acute ischemic cerebrovascular diseases.