The influence of maternal diet on offspring's gut microbiota in early life.

BACKGROUND: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. OBJECTIVE: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. CONCLUSION: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Outer membrane vesicles induce the mussel plantigrade settlement via regulation of c-di-GMP.

Despite the importance of outer membrane vesicles (OMVs) in benthic animal settlement, the underlying molecular mechanism remains elusive. Here, the impact of OMVs and OMVs synthesis-related tolB gene in Mytilus coruscus plantigrade settlement was tested. The OMVs were extracted from Pseudoalteromonas marina through density gradient centrifugation, and a tolB knockout strain, achieved by homologous recombination, was utilized for the investigation. Our results demonstrated that OMVs could significantly enhance M. coruscus plantigrades settlement. Deleting the tolB resulted in downregulation of c-di-GMP, accompanied by a reduction of OMV production, a decline in bacterial motility and increasing biofilm-forming ability. Enzyme treatment resulted in a 61.11% reduction in OMV-inducing activity and a 94.87% reduction in LPS content. Thus, OMVs regulate mussel settlement via LPS, and c-di-GMP is responsible for the OMV-inducing capacity. These findings provide new insights into the interactions between bacteria and mussels.

Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms.

Plant exosome-like nanovesicles, being innately replete with bioactive lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional characteristics as natural nanocarriers. Furthermore, their compelling physicochemical traits underpin their modulative role in physiological processes, all of which have fostered the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the ever-stringent demands of current clinical challenges. This review systemically deals with various facets of plant exosome-like nanovesicles ranging from their origin and isolation to identification of morphological composition, biological functions, and cargo-loading mechanisms. Efforts are made to encompass their biotherapeutic roles by elucidating their immunological modulating, anti-tumor, regenerative, and anti-inflammatory roles. We also shed light on re-engineering these nanovesicles into robust, innocuous, and non-immunogenic nanovectors for drug delivery through multiple stringent biological hindrances to various targeted organs such as intestine and brain. Finally, recent advances centered around plant exosome-like nanovesicles along with new insights into transdermal, transmembrane and targeting mechanisms of these vesicles are also elucidated. We expect that the continuing development of plant exosome-like nanovesicle-based therapeutic and delivery nanoplatforms will promote their clinical applications.

Implementation of perioperative breathing exercises and its effect on postoperative pulmonary complications and long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery: A randomized controlled trial.

OBJECTIVE: This study was to investigate the impact of breathing exercises on recovery in elderly patients receiving laparoscopic colorectal surgery. DESIGN: A prospective randomized controlled trial. SETTING: University hospital. SUBJECT: A total of 264 elder patients undergoing laparoscopic colorectal surgery participated in this study. INTERVENTION: Patients in intervention group received respiratory-related exercises based on standardized enhanced recovery after surgery strategies from admission to 90 days after surgery. The control group received perioperative standardized enhanced recovery after surgery strategies without formatted breathing exercises. MAIN MEASURES: The primary outcome was the incidence of postoperative pulmonary complications. The secondary outcomes included 6-minute walking distance, surgery-related complications, length of stay, mortality postoperatively, and hospitalization costs. RESULTS: Completion rate of breathing exercise in intervention group was over 80% till 90 days postoperatively. The incidence of postoperative pulmonary complications was lower in breathing exercises group (17/132 [12.9%] vs. 43/132 [32.6%], p < 0.001). The mean value of 6-minute walking distance increased more in intervention group compared with baseline values preoperatively (44.2 ± 4.3 vs. 3.2 ± 0.2, p < 0.001). On 90 days postoperatively, the mean value of 6-minute walking distance in breathing exercises group increased by 18.8 m compared with its baseline (557.0 ± 133.5 vs. 538.2 ± 112.7, p = 0.022), while that of control group decreased by 53.2 m from baseline (481.9 ± 102.5 vs. 535.1 ± 123.4, p < 0.001). Patients who received breathing exercises had shorter length of stay and lower hospitalization costs (p < 0.050). CONCLUSIONS: Perioperative breathing exercises helped prevent postoperative pulmonary complications and improve long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery.

Plant Exosomes As Novel Nanoplatforms for MicroRNA Transfer Stimulate Neural Differentiation of Stem Cells In Vitro and In Vivo.

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.

Fecal Fusobacterium nucleatum harbored virulence gene fadA are associated with ulcerative colitis and clinical outcomes.

OBJECT: Fusobacterium nucleatum (F.nucleatum), a gram-negative, obligately anaerobe of oral commensal，has been regarded as culprit of periodontal diseases previously and is being unveiled as possible pathogen of gastrointestinal disorders. The key virulence factor of F.nucleatum is FadA adhesin for binding and invading of the host's epithelial cells. Here, we detected fecal F.nucleatum and virulence gene fadA in patients with ulcerative colitis(UC) and evaluated the clinical relevance with UC. METHODS AND SUBJECTS: A total of 310 subjects were enrolled including 100 patients with UC, 70 healthy controls (HC), 70 patients with irritable bowel syndrome subtype diarrhea(IBS-D), and 70 colorectal cancer patients(CRC). Stool samples of UC patients compared with healthy controls as well as IBS-D and CRC patients were collected for Polymerase Chain Reaction(PCR) detection of F.nucleatum (based on 16s rRNA) and virulence gene fadA. RESULTS: The detection rate of 16s rRNA based PCR for F.nucleatum of UC patients(39/100, 39.00%) and CRC(26/70, 37.14%) patients are significantly higher than HC (12/70, 17.14%, P < 0.01) and IBS-D patients (14/70, 20.00%, P < 0.01). Moreover, 19 samples were detected fadA positive from 39 F.nucleatum positive samples of UC patients (19/39, 48.72%), which is significantly higher than HC(2/12, 16.66%, P < 0.05). There were 3 samples detected fadA positive from 14 F.nucleatum positive samples of IBS-D patients(3/14, 21.43%) and 13 out of 26(50.00%) of CRC patients, which were both no significant differences compared with UC patients(21.4% vs 48.72%, P > 0.05; 50.00% vs 48.72%, P > 0.05). For both F.nucleatum and fadA gene positive patients, there were no statistical significances between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells(WBC), and hemoglobin compared with negative patients(defined by either F.nucleatum or fadA negative, or both negative). However, it is worth noting that detection rate of F.nucleatum with virulence gene fadA in patients of severe ulcerative colitis was significantly higher than patients with mild and moderate colitis(28.89% vs 10.91%, P < 0.05). In addition, the fecal F.nucleatum and fadA gene positive patients were more likely to have pancolitis other than left-sided colitis(pancolitis/left-sided colitis: 26.92% vs 10.42%, P < 0.05). CONCLUSIONS: The presence of F.nucleatum and fadA gene increased in UC patients, especially in patients with severe colitis and pancolitis. Strains of F.nucleatum harbored virulence gene fadA are suggested to play a role in the pathogenesis of UC.

[Research progress on role of Chinese medicinal materials and their topical preparations in wound healing by regulating cytokines and growth factors].

Delayed-or non-healing wounds caused by trauma, surgical procedures, acute diseases, or chronic diseases, and proli-ferating scar have a serious impact on patients' quality of life and increase the economic and psychological burden on their families. Therefore, how to accelerate wound healing and obtain satisfactory aesthetic results is of great concern to researchers and is an urgent clinical problem to be solved. In recent years, the mechanisms of Chinese medicinal materials in accelerating wound healing and inhi-biting scar formation by regulating cytokines have been clarified, which provides a scientific basis for revealing the efficacy of Chinese medicinal materials against clinical trauma. This review focuses on the therapeutic effects of active ingredients, extracts, and topical preparations of Chinese medicinal materials through regulating cytokines in the inflammation, proliferation, and remodeling phases of wound healing. It is expected to provide evidence for the application of Chinese medicinal materials in wound therapy.

Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma.

BACKGROUND & AIMS: The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and developing immunotherapy. METHODS: We combined whole-exome/transcriptome sequencing, multiplex immunostaining, immunopeptidomes, T cell receptor (TCR) sequencing and bioinformatic analyses of 47 tumors from 15 patients with HCC and multifocal lesions. RESULTS: IM and MO demonstrated distinct clonal architecture, mutational spectrum and genetic susceptibility. The immune microenvironment also displayed spatiotemporal heterogeneity, such as less T cell and more M2 macrophage infiltration in IM and higher expression of inhibitory immune checkpoints in MO. Similar to mutational profiles, shared neoantigens and TCR repertoires among tumors from the same patients were abundant in IM but scarce in MO. Combining neoantigen prediction and immunopeptidomes identified T cell-specific neoepitopes and achieved a high verification rate in vitro. Immunoediting mainly occurred in MO but not IM, due to the relatively low immune infiltration. Loss of heterozygosity of human leukocyte antigen (HLA) alleles, identified in 17% of multifocal HCC, hampered the ability of major histocompatibility complex to present neoantigens, especially in IM. An integrated analysis of Immunoscore, immunoediting, TCR clonality and HLA loss of heterozygosity in each tumor could stratify patients into 2 groups based on whether they have a high or low risk of recurrence (p = 0.038). CONCLUSION: Our study comprehensively characterized the genetic structure, neoepitope landscape, T cell profile and immunoediting status that collectively shape tumor evolution and could be used to optimize personalized immunotherapies for multifocal HCC. LAY SUMMARY: Immunogenomic features of multifocal hepatocellular carcinoma (HCC) are important for understanding immune-escape mechanisms and developing more effective immunotherapy. Herein, comprehensive immunogenomic characterization showed that diverse genomic structures within multifocal HCC would leave footprints on the immune landscape. Only a few tumors were under the control of immunosurveillance, while others evaded the immune system through multiple mechanisms that led to poor prognosis. Our study revealed heterogeneous immunogenomic landscapes and immune-constrained tumor evolution, the understanding of which could be used to optimize personalized immunotherapies for multifocal HCC.

A bacterial polysaccharide biosynthesis-related gene inversely regulates larval settlement and metamorphosis of Mytilus coruscus.

Larval settlement and metamorphosis is essential for the development of marine invertebrates. Although polysaccharides are involved in larval settlement and metamorphosis of Mytilus coruscus, the molecular basis of polysaccharides underlying this progression remains largely unknown. Here, the roles of the polysaccharide biosynthesis-related gene 01912 of Pseudoalteromonas marina ECSMB14103 in the regulation of larval settlement and metamorphosis were examined by gene-knockout technique. Compared with biofilms (BFs) of the wild-type P. marina, Δ01912 BFs with a higher colanic acid (CA) content showed a higher inducing activity on larval settlement and metamorphosis. Deletion of the 01912 gene caused an increase in c-di-GMP levels, accompanied by a decrease in the motility, an increase in cell aggregation, and overproduction of CA. Thus, the bacterial polysaccharide biosynthesis-related gene 01912 may regulate mussel settlement by producing CA via the coordination of c-di-GMP. This work provides a deeper insight into the molecular mechanism of polysaccharides in modulating mussel settlement.

The Flagellar Gene Regulates Biofilm Formation and Mussel Larval Settlement and Metamorphosis.

Biofilms are critical components of most marine systems and provide biochemical cues that can significantly impact overall community composition. Although progress has been made in the bacteria-animal interaction, the molecular basis of modulation of settlement and metamorphosis in most marine animals by bacteria is poorly understood. Here, Pseudoalteromonas marina showing inducing activity on mussel settlement and metamorphosis was chosen as a model to clarify the mechanism that regulates the bacteria-mussel interaction. We constructed a flagellin synthetic protein gene fliP deletion mutant of P. marina and checked whether deficiency of fliP gene will impact inducing activity, motility, and extracellular polymeric substances of biofilms. Furthermore, we examined the effect of flagellar proteins extracted from bacteria on larval settlement and metamorphosis. The deletion of the fliP gene caused the loss of the flagella structure and motility of the ∆fliP strain. Deficiency of the fliP gene promoted the biofilm formation and changed biofilm matrix by reducing ß-polysaccharides and increasing extracellular proteins and finally reduced biofilm-inducing activities. Flagellar protein extract promoted mussel metamorphosis, and ∆fliP biofilms combined with additional flagellar proteins induced similar settlement and metamorphosis rate compared to that of the wild-type strain. These findings provide novel insight on the molecular interactions between bacteria and mussels.

Two toll-like receptors identified in the mantle of Mytilus coruscus are abundant in haemocytes.

Toll-like receptors (TLRs) are a large family of pattern recognition receptors (PRRs) that play a critical role in innate immunity. TLRs are activated when they recognize microbial associated molecular patterns (MAMPs) of bacteria, viruses, or fungus. In the present study, two TLRs were isolated from the mantle of the hard-shelled mussel (Mytilus coruscus) and designated McTLR2 and McTLR3 based on their sequence similarity and phylogenetic clustering with Crassostrea gigas, CgiTLR2 and CgiTLR3, respectively. Quantitative RT-PCR analysis demonstrated that McTLR2 and McTLR3 were constitutively expressed in many tissues but at low abundance.

Gender, Age, and Concomitant Diseases of Colorectal Diverticulum in China: A Study of 7,964 Cases.

AIM: To analyze the epidemiological features of colorectal diverticulum (CRD) in China. METHODS: We retrospectively analyzed CRD patients in 8 tertiary hospitals located in 5 regions of China from 2000 to 2016. The detection rates, number and distribution, demographic information, concomitant disorders, and their associations were investigated. RESULTS: Of 3,446,118 cases, 7,964 (2.3%) were CRD with a mean age of 56 years (11-92 years). The detection rate increased yearly and with increasing age. Males had a higher detection rate than females (3.0 vs. 1.47%, p < 0.01) and 1.8-times higher increase rate. The detection rate increased with age; however, females of > 60 years had a 2.8-times increasing rate than males. CRD occurred most frequently in the right-side colon, followed by rectum. Multiple diverticula were common in males and increased with age, with a 3-times higher increase rate than single lesion. Single-segment CRD occurred more frequently in males than in females (80.1 vs. 76.4%, p < 0.01). Concurred colon polyps were seen in 51.05% cases. CONCLUSION: CRD detection rates increased annually and with age, particularly in senior females in China. Multiple diverticula were common in males and increased with age. CRD was predominant in the right-side colon. Polyps are the most common comorbidity associated with CRD.

Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo.

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.

Effects of the nontourniquet combined with controlled hypotension technique on pain and long-term prognosis in elderly patients after total knee arthroplasty: a randomized controlled study.

PURPOSE: The aim of this study was to confirm the alleviating effects of the nontourniquet technique on the postoperative acute and chronic pain of patients after total knee arthroplasty (TKA). METHODS: 122 elderly patients undergoing TKA were randomly divided into two groups: group T (n = 58) and group H (n = 64). An electronic inflatable tourniquet was used during TKA in group T. The patients in group H received controlled hypotension but without tourniquet use during the operation. The numeric rating scale (NRS) score was used to evaluate pain level on day 1, day 2, day 3 and day 7 after the operation, and the incidence of chronic pain was judged at 3-month and 1-year follow-ups, and functional recovery of the knee joint was estimated by the active range of knee joint motion (AROM) at the same time points. Cognitive function was assessed by the montreal cognitive assessment scale (MoCA) for 7 days after operation. RESULTS: There were no significant differences in the NRS scores and AROM for 7 days after surgery. The incidence rate of chronic pain in group H (25.0%) was lower than that in group T (41.4%) and the AROM in group H was greater at one year follow-up. The MoCA score in group H was lower than that in group T on day 1 and day 2. CONCLUSION: The nontourniquet combined with controlled hypotension technique can alleviate chronic pain and promote the long-term rehabilitation of patients after TKA.

Evidence based anti-osteoporosis effects of Periplaneta americana L on osteoblasts, osteoclasts, vascular endothelial cells and bone marrow derived mesenchymal stem cells.

BACKGROUND: Kangfuxin (KFX) is the ethanol extract of Periplaneta americana L, which has been widely used in the Traditional Chinese Medicine for the repair and regeneration of injured organ and tissues with long history. This study is to investigate the influence of KFX in the various cellular activities and evaluate the anti-osteoporosis potential of KFX. METHODS: The influence of the KFX in the cellular activities, including: 1) migration, osteocalcin secretion of osteoblasts; 2) apoptosis of osteoclasts; 3) migration and tube formation of human umbilical vein endothelial cell (HUVEC); and 4) proliferation, cell cycle regulation and migration of bone marrow mesenchymal stem cells (BMSCs), were investigated systematically. RESULTS: KFX was shown to significantly 1) Promote of the migration of osteoblasts, HUVEC, and BMSCs; 2) Increase the secretion of osteocalcin and mineralization of osteoblasts; 3) Accelerate the apoptosis of osteoclasts; 4) Stimulate the proliferation and regulate the cell cycle of BMSCs. CONCLUSION: Taken together, these results provide the evidence for the osteogenesis, anti-osteoporosis and angiogenesis effects of KFX, with the mechanism of activating the bone formation through stimulating the osteoblasts and HUVECs, as well as inhibiting the bone absorption by inhibiting the osteoclasts activities. The KFX was definitely shown a promising bone turnover agent with great potential for anti-osteoporosis treatment.

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

The overlap of upper functional gastrointestinal disorders with irritable bowel syndrome in Chinese outpatients: A multicenter study.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common functional bowel disease, and the overlap with upper functional gastrointestinal disorders (FGIDs) is popular. However, the coexistent upper GI symptom profiles, upper FGID spectra, and related risk factors among IBS subjects remain unclear in mainland of China. METHODS: Consecutive patients from the outpatient gastroenterology clinics of three tertiary hospitals in China were enrolled in this multicenter study. All upper GI symptoms occurring at least once a week in the last 3 months were recorded. Diagnostic criteria of functional esophageal, gastroduodenal disorders and IBS were based on Rome III criteria. Risk factors were assessed using a multivariate logistic regression model. RESULTS: Of the 8906 consecutive patients, 751 patients met Rome III criteria for IBS and 735 IBS patients participated in the interview. Postprandial fullness (30.6%), belching (27.1%), and regurgitation (21.8%) were the three most prevalent upper GI symptoms in IBS. Functional dyspepsia (FD, 36.7%), belching disorders (27.1%), and functional heartburn (16.3%) were the three most frequent upper FGID in IBS patients. Female sex, divorced or widowed versus married status, defecation straining, reduced bowel movement, mixed IBS, abdominal distention, mild abdominal pain, moderate discomfort were positively associated with IBS-FD overlap. Female sex, drinking, moderate discomfort, and mild to moderate distension were independent risk factors for IBS-belching disorder overlap. CONCLUSIONS: The study provides detailed overlap spectra of upper FGID with IBS. Mixed IBS is an important risk factor for IBS-FD overlap, which deserved more concern.

Adult Stem Cells Seeded on Electrospinning Silk Fibroin Nanofiberous Scaffold Enhance Wound Repair and Regeneration.

Development of novel strategy stimulating the healing with skin appendages regeneration is the critical goal for wound therapy. In this study, influence of the transplantation of bone marrow derived mesenchymal stem cells (MSCs) and epidermal stem cells (ESCs) with the nanofiberous scaffold prepared from silk fibroin protein in wound re-epithelization, collagen synthesis, as well as the skin appendages regeneration were investigated. It was shown that both the transplantation of MSCs and ESCs could significantly accelerate the skin re-epithelization, stimulate the collagen synthesis. Furthermore, the regenerative features of MSCs and ESCs in activating the blood vessels and hair follicles formation, respectively were suggested. These results demonstrated that the electrospinning nanofiberous scaffold is an advantageous carrier for the cells transplantation, but also provided the experimental proofs for the application of MSCs and ESCs as promising therapeutics in skin tissue engineering.

Effects of low-dose ketamine combined with propofol on phosphorylation of AMPA receptor GluR1 subunit and GABAA receptor in hippocampus of stressed rats receiving electroconvulsive shock.

OBJECTIVES: To investigate the effects of low-dose ketamine combined with propofol on the antidepressant efficacy in stressed rats undergoing electroconvulsive shock (ECS) and its impact on phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit glutamate receptor 1 (GluR1) and γ-aminobutyric acid receptor subunit A (GABAAR). METHODS: Sprague-Dawley rats were stressed by chronic unpredictable mild stress. Fifty stressed rats were randomly divided into 5 groups (n = 10 per group): depression group (with no application, group D), ECS group (applied with ECS after intraperitoneal injection of isotonic sodium chloride solution, 8 mL/kg, group E), ketamine + ECS group (applied with ECS after intraperitoneal injection of ketamine, 10 mg/kg, group KE), propofol + ECS group (applied with ECS after intraperitoneal injection of propofol, 80 mg/kg, group PE), and ketamine + propofol + ECS group (applied with ECS after intraperitoneal injection of ketamine, 10 mg/kg, and propofol, 80 mg/kg, group KPE). All groups except group D underwent ECS once a day for 7 consecutive days. Sucrose preference test, open-field test, and Morris water maze were performed to assess the depressive behavior. Phosphorylation of GluR1 and GABAAR were evaluated by Western blot. RESULTS: Compared with group D, sucrose preference percentage and open-field scores were increased after ECS application in the 4 other groups; rats in group E reported prolonged escape latency and shortened space exploration time, whereas the escape latency were decreased and space exploration time were prolonged in group KPE; the ratio of p-GluR1/p-GABAAR in hippocampus were increased in the 4 other groups. When using group E as control, rats in group KPE exhibited higher sucrose preference percentage and open-field scores; the escape latency was shortened and space exploration time was prolonged in groups KE, PE, and KPE; the ratio of p-GluR1/p-GABAAR in the hippocampus was up-regulated in groups KE and KPE. When compared with groups KE and PE, the rats in group KPE exhibited higher sucrose preference percentage and open-field scores, the escape latency of group KPE was shortened and space exploration time was prolonged, the ratio of p-GluR1/p-GABAAR in the hippocampus of group KEP is between those of groups KE and PE. CONCLUSIONS: Low-dose ketamine combined with propofol may play a role in enhancing the antidepressant efficacy of ECS in stressed rats, ameliorating the cognitive impairment associated with ECS by balancing the expression of p-GluR1 and p-GABAAR in the hippocampus of stressed rats.

Dissolution difference of ginsenosides from ultrafine granular powder and common powder traditional pieces of Panacis Quinquefolii Radix in vitro.

The dissolution of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces in water and simulated gastric juice in vitro was compared, and the effect of particles size of Panacis Quinquefolii Radix on the dissolution was studied. HPLC method was used for determination of five ginsenosides including Rg1, Re, Rb1, Rc and Rd from ultrafine granular powder and common powder, traditional pieces of Panacis Quinquefolii Radix at different points in time, furthermore, the dissolution curves of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces were obtained. The dissolution characteristics of the three Panacis Quinquefolii Radix forms were also compared in this study. According to the results, the dissolution rates of ginsenosides from ultrafine granular powder exceeded 90% of the total content with 5 min, significantly higher than that of the other two forms in water in vitro. At the same time, the dissolved amount of the ultrafine granular powder was fourteen percent higher than that of the traditional pieces and eight percent higher than that of the common powder. Under the condition of simulated gastric juice in vitro, the dissolution rates of ginsenosides from ultrafine granular powder were little lower than that of the other two, but the maximum dissolved amount of the former was fourteen percent higher than that of the common powder and five percent higher than that of the extracts. Therefore the conclusion is that micronization of Panacis Quinquefolii Radix contributed to dissolution of effective components.