Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson's disease and neuronal damage through inhibition of microglia.

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson's disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson's disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson's disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1ß and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson's disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.

Expression of recombinant human Apolipoprotein A-IMilano in Nicotiana tabacum.

Apolipoprotein A-IMilano (Apo A-IMilano) is a natural mutant of Apolipoprotein. It is currently the only protein that can clear arterial wall thrombus deposits and promptly alleviate acute myocardial ischemia. Apo A-IMilano is considered as the most promising therapeutic protein for treating atherosclerotic diseases without obvious toxic or side effects. However, the current biopharmaceutical platforms are not efficient for developing Apo A-IMilano. The objectives of this research were to express Apo A-IMilano using the genetic transformation ability of N. tabacum. The method is to clone the coding sequence of Apo A-IMilano into the plant binary expression vector pCHF3 with a Flag/His6/GFP tag. The constructed plasmid was transformed into N. tabacum by a modified agrobacterium-mediated method, and transformants were selected under antibiotic stress. PCR, RT-qPCR, western blot and co-localization analysis was used to further verify the resistant N. tabacum. The stable expression and transient expression of N. tabacum were established, and the pure product of Apo A-IMilano was obtained through protein A/G agarose. The results showed that Apo A-IMilano was expressed in N. tabacum with a yield of 0.05 mg/g leaf weight and the purity was 90.58% ± 1.65. The obtained Apo A-IMilano protein was subjected to amino acid sequencing. Compared with the theoretical sequence of Apo A-IMilano, the amino acid coverage was 86%, it is also found that Cysteine replaces Arginine at position 173, which indicates that Apo A-IMilano, a mutant of Apo A-I, is accurately expressed in N. tabacum. The purified Apo A-IMilano protein had a lipid binding activity. The established genetic modification N. tabacum will provide a cost-effective system for the production of Apo A-IMilano. Regarding the rapid propagation of N. tabacum, this system provides the possibility of large-scale production and accelerated clinical translation of Apo A-IMilano.

Mixed porokeratosis with a novel mevalonate kinase gene mutation: A case report.

BACKGROUND: Porokeratosis is a rare, acquired, or inherited disorder of keratinization. There are numerous clinical types of porokeratosis and they can coexist in one patient and multiple members of an affected family. However, coexistence of disseminated superficial actinic porokeratosis (DSAP) and porokeratosis ptychotropica (Ppt) is rare. CASE SUMMARY: A 45-year-old man presented with long-standing skin lesions. Physical examination identified numerous small, brown 2-mm to 4-mm patches on his face and several hyperkeratotic, verrucous plaques on his trunk and extremities. His father and one of his brothers also had similar lesions for years. Skin biopsies indicated a cornoid lamella in the epidermis. We identified c.155G>A mutation in the mevalonate kinase (MVK) gene, which converted a serine residue to asparagine (p.Ser52Asn) and was causative for porokeratosis in this family. A clinicopathologic diagnosis of DSAP and Ppt with a novel MVK gene mutation was made. The hyperkeratotic plaques on the patient's scrotum were completely removed more than 10 times using a microwave knife. CONCLUSION: An unusual case of DSAP coexisting with Ppt harbored a novel MVK gene mutation also present in the patient's family.

Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy.

Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

Photo-enhanced gas sensing of SnS2 with nanoscale defects.

Recently a SnS2 based NO2 gas sensor with a 30 ppb detection limit was demonstrated but this required high operation temperatures. Concurrently, SnS2 grown by chemical vapor deposition is known to naturally contain nanoscale defects, which could be exploited. Here, we significantly enhance the performance of a NO2 gas sensor based on SnS2 with nanoscale defects by photon illumination, and a detection limit of 2.5 ppb is achieved at room temperature. Using a classical Langmuir model and density functional theory simulations, we show S vacancies work as additional adsorption sites with fast adsorption times, higher adsorption energies, and an order of magnitude higher resistance change compared with pristine SnS2. More interestingly, when electron-hole pairs are excited by photon illumination, the average adsorption time first increases and then decreases with NO2 concentration, while the average desorption time always decreases with NO2 concentration. Our results give a deep understanding of photo-enhanced gas sensing of SnS2 with nanoscale defects, and thus open an interesting window for the design of high performance gas sensing devices based on 2D materials.

The prognostic value of C-reactive protein/albumin ratio in human malignancies: an updated meta-analysis.

PURPOSE: This study aims to investigate the prognostic value of pretreatment C-reactive protein/albumin ratio (CAR) in human malignancies by an updated meta-analysis. METHODS: PubMed, Web of Science, Cochrane Library and Wanfang databases were searched. Pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were used as effective values. RESULTS: A total of 25 studies with 12,097 patients were included in this meta-analysis. Pooled results showed that high pretreatment CAR was associated with poor overall survival (OS) (HR =1.99, 95% CI: 1.65-2.40, P=0.000) and poor disease-free survival (HR =1.55, 95% CI: 1.34-1.79, P=0.000). In addition, high pretreatment CAR was associated with increased 5-year mortality (OR =2.74, 95% CI: 2.11-3.55, P=0.000). Moreover, subgroup analysis demonstrated that high CAR was associated with poor OS despite variations in publication year, country, sample size, CAR cut-off value and treatment. However, high CAR was associated with poor OS in human malignancies except colorectal cancer (HR =1.64, 95% CI: 0.96-2.80, P=0.069). CONCLUSION: High pretreatment CAR indicates poor prognosis in human malignancies except colorectal cancer. Thus, pretreatment CAR serves as a prognostic marker in human malignancies and could be used in the evaluation of prognosis in clinical work.

Novel Mutations in PSENEN Gene in Two Chinese Acne Inversa Families Manifested as Familial Multiple Comedones and Dowling-Degos Disease.

BACKGROUND: Acne inversa (AI), also called hidradenitis suppurativa, is a chronic, inflammatory, recurrent skin disease of the hair follicle. Familial AI shows autosomal-dominant inheritance caused by mutations in the γ-secretase genes. This study was aimed to identify the specific mutations in the γ-secretase genes in two Chinese families with AI. METHODS: In this study, two Chinese families with AI were investigated. All the affected individuals in the two families mainly manifested with multiple comedones, pitted scars, and a few inflammatory nodules on their face, neck, trunk, axilla, buttocks, upper arms, and thighs. Reticulate pigmentation in the flexures areas resembled Dowling-Degos disease clinically and pathologically. In addition, one of the affected individuals developed anal canal squamous cell carcinoma. Molecular mutation analysis of γ-secretase genes including PSENEN, PSEN1, and NCSTN was performed by polymerase chain reaction and direct DNA sequencing. RESULTS: Two novel mutations of PSENEN gene were identified, including a heterozygous missense mutation c.194T>G (p.L65R) and a splice site mutation c.167-2A>G. CONCLUSIONS: The identification of the two mutations could expand the spectrum of mutations in the γ-secretase genes underlying AI and provide valuable information for further study of genotype-phenotype correlations.

[Relationship between apoptotic effect of Resveratrol on KG-1 cells and expression of bcl-2/bax].

This study was aimed to explore the apoptotic effect of Resveratrol (RES) on KG-1 cells and the expression of bcl-2/bax in vitro, and to clarify the possible mechanism of apoptotic effect of RES on leukemia cells. After treating with different concentrations of RES, the suppressive effect of RES on proliferation of KG-1 cells was analyzed by MTT method. Transmission electron microscope technique were used to detect the apoptosis status of KG-1 cells. The cell cycle and apoptosis percentage of KG-1 cells treated with RES were detected by flow cytometry. The expressions of bcl-2, bax mRNA and protein were assessed by semiquantitative RT-PCR and flow cytometry. The results showed that RES could obviously inhibit proliferation of KG-1 cells (p < 0.05). Compared with the control group, the cell number in S phase of KG-1 cells treated with RES increased (p < 0.05), the apoptosis rate enhanced significantly (p < 0.01) and the expression level was down-regulated, while expression level of bax was obviously up-regulated (p < 0.01). It is concluded that RES significantly induces apoptosis of KG-1 cells in vitro, which is probably related to the down-regulation of bcl-2 expression and up-regulation of bax expression.