Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model.

BACKGROUND: Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS). METHODS: ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence. RESULTS: Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1ß, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD. CONCLUSIONS: Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis.

Traditional chinese medicine syndromes classification associates with tumor cell and microenvironment heterogeneity in colorectal cancer: a single cell RNA sequencing analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. This study is to investigate the correlation and significance of tumor heterogeneity and TCM syndromes classification in CRC. METHODS: In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC. RESULTS: The results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes in Excess and Deficiency syndrome classification in CRC (P < 0.01). CONCLUSIONS: The Excess and Deficiency syndromes classification may be related to tumor heterogeneity and its microenvironment in CRC.

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: a prospective case-control study.

BACKGROUND: Complex cryptoglandular perianal fistula (CPAF) is a kind of anal fistula that may cause anal incontinence after surgery. Minimally invasive surgery of anal fistula is constantly emerging. Over the past 20 years, there are several sphincter-sparing surgeries, one of which is autologous adipose-derived stem cell (ADSC) transplantation. However, to date, there is no study regarding the treatment of complex CPAF with ADSC in China. This is the first study in China on the treatment of complex CPAF with ADSC to evaluate its safety and efficacy. METHODS: Totally, 24 patients with complex CPAF were enrolled in this prospective case-control study from January 2018 to December 2019 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided into ADSC group and endorectal advancement flap (ERAF) group according to their desire. The healing of fistulas (healing of all treated fistulas at baseline, confirmed by doctor's clinical assessment and magnetic resonance imaging or transrectal ultrasonography) was evaluated at week 12 after treatment. In addition to their safety evaluation based on adverse events monitored at each follow-up, the patients were also asked to complete some scoring scales at each follow-up including pain score with visual analog score (VAS) and anal incontinence score with Wexner score. RESULTS: The closure rates within ADSC group and ERAF group at week 12 were 54.55% (6/11) and 53.85% (7/13), respectively, without significant difference between them. VAS score in ADSC group was significantly lower than that in ERAF group at the 5th day postoperatively [1(0,2) VS 2(2,4), p = 0.011], but no differences were observed at the other time. Wexner score of all patients was not increased with no significant differences between the two groups. Adverse events were observed fewer in ADSC group (27.27%) than that in ERAF group (53.85%), but there was no significant difference between them. CONCLUSION: This study indicated safety and efficiency of ADSC for the treatment of complex CPAF in the short term, which is not inferior to that of ERAF. ADSC may provide a promised and potential treatment for complex CPAF conforming to the future of the treatment, which is reconstruction and regeneration. TRAIL REGISTRATION: ChiCTR, ChiCTR1800014599. Registered 23 January 2018-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=24548.

Autologous adipose-derived stem cells for the treatment of Crohn's fistula-in-ano: an open-label, controlled trial.

BACKGROUND: Crohn's fistula-in-ano is a refractory disease in colorectal and anal surgery. Although autologous adipose-derived stem cell (ADSC) has been used in the treatment of Crohn's fistula-in-ano because of its convenience, non-incision of normal tissue, good tolerance, repeatability, quick recovery, less pain, less damage to anal function, and high quality of life during the perioperative period, there are no reports of its use in China. This is the first clinical trial in China on the treatment of Crohn's fistula-in-ano with ADSC to evaluate its efficacy and safety. METHODS: A total of 22 patients with Crohn's fistula-in-ano were enrolled in this study from January 2018 to October 2018 in the Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided (1:1) into an observation group (ADSC) and a control group (incision-thread-drawing procedure). Primary efficacy endpoint evaluated at months 3, 6, and 12 was the closure of fistulas (closure of all treated fistulas at baseline, confirmed by doctor's clinical assessment and magnetic resonance imaging or transrectal ultrasonography). The patients additionally completed some scoring scales at each follow-up including simplified Crohn's Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), pain scores with visual analog score (VAS), and Wexner score. The data of inflammatory indexes were also collected. RESULTS: The healing rates of the observation group and the control group at months 3, 6, and 12 were as follows: 10/11(90.9%) vs 5/11(45.5%), 8/11(72.7%) vs 6/11(54.5%), and 7/11(63.6%) vs 6/11(54.5%), respectively. There was no statistical difference between the two groups. In addition, the improvement in simplified CDAI, PDAI, IBDQ, VAS, and Wexner score of the observation group were better than that of the control group at each follow-up. The inflammatory indexes decreased in both the observation group and the control group at 3 months follow-up. And there were no significant differences in the changes of inflammatory indexes between two groups at month 3 compared with the baseline. Safety was maintained throughout month 12, and adverse events occurred in 63.6% of patients in the observation group and 100% patients in the control group. And no adverse event associated with ADSC injection was observed in the study. CONCLUSION: ADSC is a feasible and effective treatment for Crohn's fistula-in-ano, compared with traditional incision and thread-drawing. It can protect anal function of patients, relieve pain, allow quick recovery, be well-tolerated, and improve the quality of life during perioperative period. TRIAL REGISTRATION: China Clinical Trials Registry, No. ChiCTR1800014599. Registered 23 January 2018.

Primary neuroendocrine tumor in the presacral region: A case report.

BACKGROUND: Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years. CASE SUMMARY: The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found. CONCLUSION: Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

Extranodal natural killer/T-cell lymphoma (nasal type) presenting as a perianal abscess: A case report.

BACKGROUND: Extranodal natural killer (NK) T-cell lymphoma (ENKTL), nasal type is a rare subtype of extranodal non-Hodgkin lymphoma characterized by vascular damage and necrosis. The lesions usually present in the nasal cavity and adjacent tissues, however, the disease originates from the gastrointestinal or genitourinary tract in 25% of cases. Since rectal involvement in ENKTL is rare, rectal symptoms in the course of ENKTL are often misdiagnosed and considered to be related to benign diseases such as rectal fistula or perianal abscess. CASE SUMMARY: We report the case of a 24-year-old Han Chinese female who initially presented with a perianal abscess that was subsequently diagnosed as nasal type ENKTL. Due to typical perianal pain, perianal abscess was diagnosed and surgical incision and drainage were performed. After recurrent, severe anal hemorrhages leading to hypovolemic shock and multiple surgeries, a diagnosis of ENKTL was made. The patient's condition gradually deteriorated, and she died shortly after initiation of chemotherapy. CONCLUSION: Systemic and neoplastic diseases should be included in the differential diagnosis of any potentially benign perianal abscess complicated with recurrent hemorrhages.

Synthesis of carbon nanofibers by CVD as a catalyst support material using atomically ordered Ni3C nanoparticles.

Atomically ordered nickel carbide (Ni3C) nanoparticles in polygonal shapes were prepared through the reduction of nickelocene. A novel type of carbon nanofiber (CNF) with twisted conformation was synthesized successfully by catalytic chemical vapor deposition (CCVD) using the obtained Ni3C nanoparticles at a relatively low temperature of 350 °C, which is below the lower limit temperature of 400 °C for the growth of CNFs using metal catalysts. The growth mechanism of the twisted CNFs from Ni3C was freshly derived based on the detailed characterizations. Compared with the growth of CNFs from Ni, graphene layers nucleate at monoatomic step edges and grow in a layer-by-layer manner, while the rotation of the polygonal Ni3C nanoparticles fabricates the twisted conformation during the CNF growth. The electrochemical activity and performance of the twisted CNFs loaded with Pt as electrode catalysts for a polymer electrolyte membrane fuel cell (PEMFC) were measured to be better than those of straight CNFs grown from Ni nanoparticles at 500 °C, since the specific surface conformation helps to make the loaded Pt more homogeneous.

Superelasticity, corrosion resistance and biocompatibility of the Ti-19Zr-10Nb-1Fe alloy.

Microstructure, mechanical properties, superelasticity and biocompatibility of a Ti-19Zr-10Nb-1Fe alloy are investigated. X-ray diffraction spectroscopy and transmission electron microscopy observations show that the as-cast Ti-19Zr-10Nb-1Fe alloy is composed of α' and ß phases, but only the ß phase exists in the as-rolled and as-quenched alloys. The tensile stress-strain tests indicate that the as-quenched alloy exhibits a good combination of mechanical properties with a large elongation of 25%, a low Young's modulus of 59 GPa and a high ultimate tensile stress of 723 MPa. Superelastic recovery behavior is found in the as-quenched alloy during tensile tests, and the corresponding maximum of superelastic strain is 4.7% at the pre-strain of 6%. A superelastic recovery of 4% with high stability is achieved after 10 cyclic loading-unloading training processes. Potentiodynamic polarization and ion release measurements indicate that the as-quenched alloy shows a lower corrosion rate in Hank's solution and a much less ion release rate in 0.9% NaCl solution than those of the NiTi alloys. Cell culture results indicate that the osteoblasts' adhesion and proliferation are similar on both the Ti-19Zr-10Nb-1Fe and NiTi alloys. A better hemocompatibility is confirmed for the as-quenched Ti-19Zr-10Nb-1Fe alloy, attributed to more stable platelet adhesion and small activation degree, and a much lower hemolysis rate compared with the NiTi alloy.

Simple synthesis of mesoporous carbon nanofibers with hierarchical nanostructure for ultrahigh lithium storage.

In this study, a simple and reproducible synthesis strategy was developed to fabricate mesoporous carbon nanofibers (MCNFs) by using dual hard templates, a porous anodic aluminum oxide (AAO) membrane, and colloidal silica (Ludox TM-40). By using commercial templates, and removing AAO and the silica simultaneously, the synthesis procedures for MCNFs are greatly simplified without the need for separate preparation or the removal of templates in sequence. With phenol resin as a carbon precursor, the as-prepared MCNFs material reveals not only high surface area and mesoporous volume but also hierarchical nanostructure composed of hollow macrochannels derived from the AAO template, large mesopores (ca. 22 nm) from the removal of silica particles and micropores from the carbonization of phenol resin. Such unique surface and structural characteristics could provide a large quantity of active sites for Li storage and facilitate fast mass transport. Moreover, a one-dimensional (1D) carbon nanofiber (CNF) nanostructure favors fast electron transfer. The as-prepared MCNF anode demonstrates ultrahigh lithium storage capacity particularly at high rates, which is much higher than that reported for the commercial graphite and also significantly higher than other nanostructured carbon materials, such as ordered mesoporous carbon CMK-3 and ordered multimodal porous carbon (OMPC).