[Analysis and monitoring of traditional Chinese medicines for tumor based on data mining].

The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.

Ptrf transgenic mice exhibit obesity and fatty liver.

Polymerase I and transcript release factor (Ptrf, also known as Cavin1) is an essential component in the biogenesis and function of caveolae. Ptrf knockout mice or patients with PTRF mutations exhibit numerous pathologies including markedly aberrant fuel metabolism, lipodystrophy and muscular dystrophy. In this study, we generated Ptrf transgenic mice to explore its function in vivo. Compared with wild-type (WT) mice, we found that the Ptrf transgenic mice showed obesity with an increased level of ALT (alanine aminotransferase) and AST (aspartate transaminase). Ptrf transgenic mice exhibited severe fat degeneration and a higher degree of fat accumulation in the liver compared with WT mice. Consistently, we found that the expression of the fat synthesis gene, Fasn, was increased in the liver of Ptrf transgenic mice. Thus, Ptrf transgenic mice would be a good model for investigating the molecular mechanism and therapeutic targets of obesity and fatty liver associated diseases.

Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation.

BACKGROUND: Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells. METHODS: Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination. RESULTS: Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity. CONCLUSIONS: This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.

Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90.

The molecular chaperone heat shock protein 90 (Hsp90) and the co-chaperone/ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) control the turnover of client proteins. How this system decides to stabilize or degrade the client proteins under particular physiological or pathological conditions is unclear. We report here a novel client protein, the SUMO2/3 protease SENP3, that is sophisticatedly regulated by CHIP and Hsp90. SENP3 is maintained at a low basal level under non-stress condition due to Hsp90-independent CHIP-mediated ubiquitination. Upon mild oxidative stress, SENP3 undergoes thiol modification, which recruits Hsp90. Hsp90/SENP3 association protects SENP3 from CHIP-mediated ubiquitination and subsequent degradation, but this effect of Hsp90 requires the presence of CHIP. Our data demonstrate for the first time that CHIP and Hsp90 interplay with a client alternately under non-stress and stress conditions, and the choice between stabilization and degradation is made by the redox state of the client. In addition, enhanced SENP3/Hsp90 association is found in cancer. These findings provide new mechanistic insight into how cells regulate the SUMO protease in response to oxidative stress.

Transgenic expression of BRCA1 disturbs hematopoietic stem and progenitor cells quiescence and function.

The balance between quiescence and proliferation of HSCs is an important regulator of hematopoiesis. Loss of quiescence frequently results in HSCs exhaustion, which underscores the importance of tight regulation of proliferation in these cells. Studies have indicated that cyclin-dependent kinases are involved in the regulation of quiescence in HSCs. BRCA1 plays an important role in the repair of DNA double-stranded breaks, cell cycle, apoptosis and transcription. BRCA1 is expressed in the bone marrow. However, the function of BRCA1 in HSCs is unknown. In our study, we generated BRCA1 transgenic mice to investigate the effects of BRCA1 on the mechanisms of quiescence and differentiation in HSCs. The results demonstrate that over-expression of BRCA1 in the bone marrow impairs the development of B lymphocytes. Furthermore, BRCA1 induced an increase in the number of LSKs, LT-HSCs, ST-HSCs and MPPs. A competitive transplantation assay found that BRCA1 transgenic mice failed to reconstitute hematopoiesis. Moreover, BRCA1 regulates the expression of p21(waf1)/cip1 and p57(kip2), which results in a loss of quiescence in LSKs. Together, over-expression of BRCA1 in bone marrow disrupted the quiescent of LSKs, induced excessive accumulation of LSKs, and disrupted differentiation of the HSCs, which acts through the down-regulated of p21(waf1)/cip1 and p57(kip2).

[Determination of five pyrethroid pesticides residues in Anoectochilus roxburghii by cloud point extraction-back extraction and GC-MS].

A method for residual determination of 5 pyrethroid pesticides in Anoectochilus roxburghii by cloud point extraction-back extraction-GC-MS was established. PEG 6000 was used as extraction agent and isooctane was used for back-extractant. The con- tent was calculated by external standard method. The linear range was from 15 to 2 000 µg x kg(-1) with the good correlation coefficients (0.955-0.999). The recoveries at spiked concentrations of 50-500 µg x kg(-1) ranged from 85.12% to 101.6%. The limit of detection and quantification of 5 pyrethroid pesticides were in the range of 0.63-3.10 µg x kg(-1) and 2.10-10.31 µg x kg(-1), respectively. The proposed method can be applied to the determination of pyrethroid pesticides residues in A. roxburghii.

SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation.

The physiological function of Sentrin/SUMO-specific proteases (SENPs) remains largely unexplored, and little is known about the regulation of SENPs themselves. Here, we show that a modest increase of reactive oxygen species (ROS) regulates SENP3 stability and localization. We found that SENP3 is continuously degraded through the ubiquitin-proteasome pathway under basal condition and that ROS inhibit this degradation. Furthermore, ROS causes SENP3 to redistribute from the nucleoli to the nucleoplasm, allowing it to regulate nuclear events. The stabilization and redistribution of SENP3 correlate with an increase in the transcriptional activity of the hypoxia-inducing factor-1 (HIF-1) under mild oxidative stress. ROS-enhanced HIF-1 transactivation is blocked by SENP3 knockdown. The de-SUMOylating activity of SENP3 is required for ROS-induced increase of HIF-1 transactivation, but the true substrate of SENP3 is the co-activator of HIF-1 alpha, p300, rather than HIF-1 alpha itself. Removing SUMO2/3 from p300 enhances its binding to HIF-1 alpha. In vivo nude mouse xenografts overexpressing SENP3 are more angiogenic. Taken together, our results identify SENP3 as a redox sensor that regulates HIF-1 transcriptional activity under oxidative stress through the de-SUMOylation of p300.

Determination of alkaloids in Sinomenium acutum by field-amplified sample stacking in capillary electrophoresis with chemiluminescene detection.

A simple and rapid capillary electrophoresis (CE) with an acidic potassium permanganate chemiluminescence (CL) detection method was developed to determine three alkaloids (curine, sinomenine and magnoflorine) simultaneously. A laboratory-built CE-CL detection interface was used. The field-amplified sample stacking technique was applied to the online concentration of alkaloids. Experimental conditions for CE separation and CL detection were investigated in detail to acquire optimum conditions. Under optimal conditions, the three alkaloids were baseline separated within 6 min, and the detection limits (S/N = 3) ranged from 0.03 µg/mL to 0.49 µg/mL. This method was successfully applied to determine the above three alkaloids in Sinomenium acutum, and the result of the determination of sinomenine was in good agreement with those given by high-performance liquid chromatography and CE methods. In addition, a possible CL reaction mechanism of sinomenine-KMnO4-H2SO4 was proposed.

Effect of spermidine on radiation-induced long-term bone marrow cell injury.

OBJECTIVE: Spermidine, a natural polyamine, possesses anti-oxidant, autophagy-regulation, and anti-aging properties. Elevated levels of oxidative stress, which was mediated the senescence of hematopoietic stem cells (HSCs) induced by radiation exposure, may further contribute to long-term myelosuppression. Therefore, this study investigated the protective effect of spermidine on the long-term damage of the hematopoietic system caused by radiation exposure. METHODS: In vitro experiments, bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice were isolated and incubated with 5 mM spermidine for 30 min, then irradiated by 2 Gy X ray. The survival rate, proliferation, and differentiation ability of BMMNCs were detected. In vivo experiment, mice received 4 Gy total body irradiation (TBI), 3 mM spermidine were administered in the drinking water every day for 14 days prior to irradiation and then continued for 30 days after irradiation. Peripheral blood, bone marrow cell typing, level of reactive oxygen species (ROS), colony-forming ability of HSC, and transplantation-reconstitution capability were detected. RESULTS: In vitro experiments, spermidine significantly improved the survival rate of BMMNCs as well as the proliferation and differentiation ability of HSCs exposure to ionizing radiation (IR). In vivo, spermidine reduced levels of ROS in HSCs; spermidine attenuated long-term myeloid differentiation deviation induced by TBI. Spermidine promoted the proliferation and differentiation ability of stem cells, but failed to ameliorate the decreased engraftment capacity of bone marrow cells in mice exposed to TBI. CONCLUSION: This study demonstrated that spermidine could promote the recovery of IR-induced inhibition of proliferation and differentiation ability of HSCs, partly through antioxidant effects. Whether combining spermidine with other radioprotectants could further increase protective efficacy and reduce the long-term bone marrow injury needs further investigation.

Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Alleviates Atherosclerotic Plaque by Inhibiting Ox-LDL Uptake, Inflammatory Reaction and Endothelial Damage in Rabbits.

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-ß levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage.

SUMO2 and SUMO3 transcription is differentially regulated by oxidative stress in an Sp1-dependent manner.

Protein SUMOylation (SUMO is small ubiquitin-related modifier) is a dynamic process that is strictly regulated under physiological and pathological conditions. However, little is known about how various intra- or extra-cellular stimuli regulate expression levels of components in the SUMO system. SUMO isoforms SUMO2 and SUMO3 can rapidly convert to be conjugated in response to a variety of cellular stresses. Owing to the limitations of sequence homology, SUMO2 and SUMO3 cannot be differentiated between and are thus referred to as SUMO2/3. Whether these two isoforms are regulated in distinct manners has never been addressed. In the present paper we report that the expression of SUMO3, but not SUMO2, can be down-regulated at the transcription level by cellular oxidative stress. In the present study, we checked SUMO2 and SUMO3 mRNA levels in cells exposed to various doses of H2O2 and in cells bearing different levels of ROS (reactive oxygen species). We found an inverse relationship between SUMO3 transcription and ROS levels. We characterized a promoter region specific for the mouse Sumo3 gene that is bound by the redox-sensitive transcription factor Sp1 (specificity protein 1) and demonstrated oxidation of Sp1, as well as suppression of Sp1-DNA binding upon oxidative stress. This revealed for the first time that the expression of SUMO2 and SUMO3 is regulated differently by ROS. These findings may enhance our understanding about the regulation of SUMOylation and also shed light on the functions of Sp1.

A comparative study of mouse bone marrow mesenchymal stem cells isolated using three easy-to-perform approaches.

Mouse bone marrow mesenchymal stem cells (mBM-MSCs) are important for preclinical tissue regeneration and repair studies. In the present study, we isolated mBM-MSCs using three easy-to-perform methods (whole bone marrow-adherent culture, density-gradient centrifugation, and bone digestion), and then compared the morphology, proliferation, differentiation, and paracrine factor profiles of the isolated mBM-MSCs. Of these three isolation methods, the bone digestion method resulted in the highest quantity of mBM-MSCs with high growth potential and moderate differentiation. Conversely, the mBM-MSCs isolated through the whole bone marrow-adherent method exhibited the lowest potency for proliferation and differentiation. The differentially expressed factors between mBM-MSCs were primarily those involved in immune responses. The highly expressed secreted factors included cytokines/members of the chemokine family, growth factors, and protein binding/proteinase activity. These findings provide a fundamental reference for development of MSC isolation methods.

Microbial Fertilization Improves Soil Health When Compared to Chemical Fumigation in Sweet Lily.

Lanzhou Lily(Lilium davidii) var. unicolor, which is also known as sweet lily in China, is used as a type of food. This lily is distributed in narrow regions, propagates asexually, cultivates perennially, and cultivates commonly in serious consecutive replant problems (CRPs). Soil fumigation is commonly used to control soil-borne disease to alleviate crops' consecutive replant problems (CRPs). However, due to the improper fumigation application, it is common to cause chemical hazard to crops. In this study, we designed a two-factor experiment to explore the bacterial and fungal community structure and some specific microbial groups in the lily rhizosphere soil after chemical versus bacterial fertilizer treatments, by using a metagenomic analysis of the treated soils. The results showed that metham-sodium soil fumigation (SMF treatment) significantly decreased plant growth, as well as it significantly decreased both soil fungal diversity and abundance at the OTUs levels, while Special 8™ microbial fertilizer supplement (MF treatment) significantly improved plant growth and increased fungal diversity and abundance. Under FM treatment, Chao1 richness and Shannon's diversity increased by 6.70% and 35.09% compared to CK (no treatment). However, the bacterial diversity and abundance were not significantly changed among these treatments. The fungal and bacterial community structure were different in all treatments. In SMF treatment, the pathogenic fungal species Fusarium oxysporum increased compared to CK, but it significantly decreased in MF treatment; in MF and MMF treatments, some beneficial bacteria groups such as the bacterial phylum Proteobacteria and its member genus Sphingomonas, as well as the fungal genus Mortierella, increased compared to CK and SFM treatments, but the harmful bacterial genera Gemmatimona was decreased, as well as the harmful fungal genus Cryptococcus. Thus, we concluded that under chemical fumigation conditions, both fungal diversity loss and overall microorganism reduction, which impair multiple ecosystem function, in conjunction with the increase of harmful fungal species such as Fusarium oxysporum, are causes for soil degradation. On the other hand, under microbial fertilizer supplement, it was the fungal diversity increase, as well as these beneficial microorganisms groups' accumulation, together with those harmful groups' depletion, played important roles in restoring and improving soil health that suffered from the chemical fumigant hazard. In addition, the bacterial phylum Proteobacteria and its member genus Sphingomonas are involved in soil health recovery and promotion. The results also emphasized that whether soil is chemically fumigated or not, beneficial microorganism supplementary is effective in ensuring soil productivity.

SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress.

Small ubiquitin-like modifier (SUMO) 2/3 is known to conjugate to substrates in response to a variety of cellular stresses. However, whether and how SUMO2/3-specific proteases are involved in de-conjugation under cell stress is unclear. Here, we show that low doses of hydrogen peroxide (H(2)O(2)) induce an increase of the SENP3 protein, which removes SUMO2/3 from promyelocytic leukemia (PML). Low dose H(2)O(2) causes SENP3 to co-localize with PML bodies and reduces the number of PML bodies in a SENP3-dependent manner. Furthermore, de-conjugation of SUMO2/3 from PML is responsible for the accelerated cell proliferation caused by low dose H(2)O(2). Knocking down PML promotes basal cell proliferation as expected. This can be reversed by reconstitution with wild-type PML but not its mutant lacking SUMOylation, indicating that only the SUMOylated PML can play an inhibitory role for cell proliferation. Thus, SENP3 appears to be a key mediator in mild oxidative stress-induced cell proliferation via regulation of the SUMOylation status of PML. Furthermore, SENP3 is over-accumulated in a variety of primary human cancers including colon adenocarcinoma in which PML is hypo-SUMOylated. These results reveal an important role of SENP3 and the SUMOylation status of PML in the regulation of cell proliferation under oxidative stress.

The effect of peptidoglycan stimulation on basophil-mediated atopic responses during pregnancy and in newborns.

BACKGROUND: Toll-like receptor (TLR) molecules play critical roles in directing the course of atopic diseases by recognizing specific microbial products that activate immune effector cell function. OBJECTIVE: We determined if basophils harvested from neonates genetically predisposed to atopic disease had different levels of TLR2 expression and determined whether putative TLR2 ligands mediated cytokine secretion. METHODS: Blood samples were collected from 10 asthmatic and 12 healthy women and their newborns. Basophil histamine was measured using the human basophil degranulation test and TLR2 expression was determined using nucleic acid hybridization in situ and flow cytometry. IL-4 levels were quantified by ELISA following allergen stimulation. RESULTS: The basophil degranulation index (DI) in granulocytes harvested from peripheral blood of asthmatic women was assessed following stimulation with either peptidoglycan (PGN) or Dermatophagoides farinae (Df) extract. The DI was significantly higher in atopic women than in healthy controls. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared with basophils purified from children born to nonatopic controls. Finally, TLR2 expression at the protein and mRNA levels was upregulated in cord blood basophils from neonates born to mothers with asthma following stimulation with PGN but not Df. CONCLUSION: These data suggested that TLR2-mediated innate immune responses play a role in augmenting allergic reactions through the modulation of basophil cytokine secretion and histamine release. Microbial components may activate basophils through TLR2 (especially for genetically predisposed infants) to release cytokines associated with an increased incidence of allergic diseases.

Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem/progenitor cell compartment.

Background: Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis through self-renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low-density lipoprotein, chylomicrons, and triglyceride-rich lipoproteins. Methods: The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence-activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL+/- HSC microenvironment were detected by transplantation assays using red fluorescent protein (RFP) transgenic mice. Results: To explore the function of LPL in HSC regulation, heterozygous LPL-knockout mice (LPL+/-) were established and analyzed by FACS. LPL+/- mice displayed decreased hematopoietic stem/progenitor cell compartments. In vitro single-cell clonogenic assays and cell-cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57KIP2 and p21WAF1/CIP1 in LPL+/- mice was upregulated. Conclusions: LPL+/- mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.

Age-related alteration in characteristics, function, and transcription features of ADSCs.

BACKGROUND AND OBJECTIVES: Adipose tissue-derived stem cells (ADSCs) autologous transplantation has been a promising strategy for aging-related disorders. However, the relationship between ADSCs senescence and organismal aging has not been clearly established. Therefore, we aimed at evaluating senescence properties of ADSCs from different age donors and to verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation. METHODS AND RESULTS: The ADSCs were obtained from 1-month-old and 20-month-old mice. The cells characteristics, functions, gene expression levels, apoptosis proportion, cell cycle, SA-ß-gal staining, and transcription features were evaluated. Compared to ADSCs from 1-month-old mice, ADSCs from 20-month-old mice exhibited some senescence-associated changes, including inhibited abilities to proliferate. Moreover, differentiation abilities, cell surface markers, and cytokines secreting differed between 1M and 20M ADSCs. SA-ß-Gal staining did not reveal differences between the two donor groups, while cells exhibited more remarkable age-related changes through continuous passages. Based on transcriptome analysis and further detection, the CCL7-CCL2-CCR2 axis is the most probable mechanism for the differences. CONCLUSIONS: ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 axis is a potential target for gene therapy to reduce the harmful effects of ADSCs from old donors. To improve on autologous transplantation, we would recommend that ADSCs should be cryopreserved in youth with a minimum number of passages or block CCL7-CCL2-CCR2 to abolish the effects of age-related alterations in ADSCs through the Chemokine signaling pathway.

Effectiveness and mechanisms of adipose-derived stem cell therapy in animal models of Parkinson's disease: a systematic review and meta-analysis.

Animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson's disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments, n = 156 animals) and rotarod performance (3 experiments, n = 54 animals) were improved (P < 0.000 01 and P = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (- 2.59; 95% CI, - 3.57 to - 1.61) when compared to that of primitive cells (- 2.18; 95% CI, - 3.29 to - 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

Therapeutic potential of human umbilical cord mesenchymal stem cells on aortic atherosclerotic plaque in a high-fat diet rabbit model.

BACKGROUND: Atherosclerosis (AS) is a complex disease caused in part by dyslipidemia and chronic inflammation. AS is associated with serious cardiovascular disease and remains the leading cause of mortality worldwide. Mesenchymal stem cells (MSCs) have evolved as an attractive therapeutic agent in various diseases including AS. Human umbilical cord MSCs (UCSCs) have been used in cell therapy trials due to their ability to differentiate and proliferate. The present study aimed to investigate the effect of UCSCs treatment on atherosclerotic plaque formation and the progression of lesions in a high-fat diet rabbit model. METHODS: Rabbits were fed a high-fat diet and then randomly divided into three groups: control, model, and treatment groups. Rabbits in the treatment group were injected with UCSCs (6 × 106 in 500 µL phosphate buffered saline) after 1 month of high-fat diet, once every 2 weeks, for 3 months. The model group was given PBS only. We analyzed serum biomarkers, used ultrasound and histopathology to detect arterial plaques and laser Doppler imaging to measure peripheral blood vessel blood filling, and analyzed the intestinal flora and metabolism. RESULTS: Histological analysis showed that the aortic plaque area was significantly reduced in the treatment group. We also found a significant decrease in macrophage accumulation and apoptosis, an increase in expression of scavenger receptors CD36 and SRA1, a decrease in uptake of modified low-density protein (ox-LDL), and a decrease in levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following UCSCs treatment. We also found that anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-ß expression increased in the aorta atherosclerotic plaque of the treatment group. UCSCs treatment improved the early peripheral blood filling, reduced the serum lipid level, and inhibited inflammation progression by regulating the intestinal flora dysbiosis caused by the high-fat diet. More specifically, levels of the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) were down-regulated in the treatment group. CONCLUSIONS: UCSCs treatment alleviated atherosclerotic plaque burden by reducing inflammation, regulating the intestinal flora and TMAO levels, and repairing the damaged endothelium.

Transcriptome profiling of five brain regions in a 6-hydroxydopamine rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease, and its pathogenesis is unclear. Previous studies mainly focus on the lesions of substantia nigra (SN) and striatum (Str) in PD. However, lesions are not limited. The olfactory bulb (OB), subventricular zone (SVZ), and hippocampus (Hippo) are also affected in PD. AIM: To reveal gene expression changes in the five brain regions (OB, SVZ, Str, SN, and Hippo), and to look for potential candidate genes and pathways that may be correlated with the pathogenesis of PD. MATERIALS AND METHODS: We established control group and 6-hydroxydopamine (6-OHDA) PD model group, and detected gene expressions in the five brain regions using RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR). We further analyzed the RNA-seq data by bioinformatics. RESULTS: We identified differentially expressed genes (DEGs) in all five brain regions. The DEGs were significantly enriched in the "dopaminergic synapse" and "retrograde endocannabinoid signaling," and Gi/o-GIRK is the shared cascade in the two pathways. We further identified Ephx2, Fam111a, and Gng2 as the potential candidate genes in the pathogenesis of PD for further studies. CONCLUSION: Our study suggested that gene expressions change in the five brain regions following exposure to 6-OHDA. The "dopaminergic synapse," "retrograde endocannabinoid signaling," and Gi/o-GIRK may be the key pathways and cascade of the synaptic damage in 6-OHDA PD rats. Ephx2, Fam111a, and Gng2 may play critical roles in the pathogenesis of PD.