A novel α,ß-unsaturated ketone inhibits leukemia cell growth as PARP1 inhibitor.

Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.

Impact of glucocorticoids and rapamycin on autophagy in Candida glabrata-infected macrophages from BALB/c mice.

Objective: In the defense against microorganisms like Candida albicans, macrophages recruit LC3(Microtubule-associated protein 1A/1B-light chain 3) to the periplasm, engaging in the elimination process through the formation of a single-membrane phagosome known as LC3-associated phagocytosis (LAP). Building on this, we propose the hypothesis that glucocorticoids may hinder macrophage phagocytosis of Candida glabrata by suppressing LAP, and rapamycin could potentially reverse this inhibitory effect. Methods: RAW264.7 cells were employed for investigating the immune response to Candida glabrata infection. Various reagents, including dexamethasone, rapamycin, and specific antibodies, were utilized in experimental setups. Assays, such as fluorescence microscopy, flow cytometry, ELISA (Enzyme-Linked Immunosorbent Assay), Western blot, and confocal microscopy, were conducted to assess phagocytosis, cytokine levels, protein expression, viability, and autophagy dynamics. Results: Glucocorticoids significantly inhibited macrophage autophagy, impairing the cells' ability to combat Candida glabrata. Conversely, rapamycin exhibited a dual role, initially inhibiting and subsequently promoting phagocytosis of Candida glabrata by macrophages. Glucocorticoids hinder macrophage autophagy in Candida glabrata infection by suppressing the MTOR pathway(mammalian target of rapamycin pathway), while the activation of MTOR pathway by Candida glabrata diminishes over time. Conclusion: Our study elucidates the intricate interplay between glucocorticoids, rapamycin, and macrophage autophagy during Candida glabrata infection. Understanding the implications of these interactions not only sheds light on the host immune response dynamics but also unveils potential therapeutic avenues for managing fungal infections.

Effects of resveratrol on macrophages after phagocytosis of Candida glabrata.

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.

Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD.

Introduction: Early recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival. Patients with severe GvHD, however, had much slower iNKT cell reconstitution relative to conventional T cells. Methods: To characterize the delay of iNKT cell reconstitution and explore its possible causes, we used a haploidentical bone marrow transplantation (haplo-BMT) mouse model with GvHD. We found the delayed recovery of thymic and peripheral iNKT cell numbers with markedly decreased thymic NKT1 subset in GvHD mice. The defective generation of thymic iNKT precursors with egress capability contributed to the reduced peripheral iNKT cells in GvHD mice. We further identified intermediate NK1.1- NKT1 precursor subpopulations under steady-state conditions and found that the differentiation of these subpopulations was impaired in the thymi of GvHD mice. Detailed characterization of iNKT precursors and thymic microenvironment showed a close association of elevated TCR/co-stimulatory signaling provided by double positive thymocytes and macrophages with defective down-regulation of proliferation, metabolism, and NKT2 signature in iNKT precursor cells. Correspondingly, NKT2 but not NKT1 differentiation was favored in GvHD mice. Discussion: These data underline the important roles of TCR and co-stimulatory signaling in the differentiation of thymic iNKT subsets under transplantation conditions.

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab-based therapy.

Amyloid light-chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single-cell level of CD3+ T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8+ T cells. In particular, we found the presence of CD8+ BM resident memory T cells (TRM ) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara-BCD, these TRM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara-based therapy in patients with AL amyloidosis promotes anti-tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis.

Single-crystalline Fe7S8/Fe3O4 coated zero-valent iron synthesized with vacuum chemical vapor deposition technique: Enhanced reductive, oxidative and photocatalytic activity for water purification.

Well-defined core/shell type single crystalline Fe7S8/Fe3O4 coated α-Fe hybrids (Fe7S8/Fe3O4@Fe) are synthesized with vacuum chemical vapor deposition (CVD) technique. The CVD process triggers conversion of naturally formed Fe3O4 layer on the surface of commercial Fe nanoparticles from amorphous into single crystalline phase. The Fe7S8/Fe3O4 coat promotes the surface affinity of dissolved oxygen and targets and rapidly transfers electrons from the Fe core to targets, which decreases water splitting on Fe7S8/Fe3O4@Fe surface and endows Fe7S8/Fe3O4@Fe with ultra-strong reducibility and improved oxidative ability under different conditions. Different with the sulfurized ZVI prepared with hydrothermal or solvothermal method, the increase of reaction solution pH is retarded due to the relieved water splitting instead of releasing H+ via oxidation of S2-/S22- on the Fe7S8 coat. The cooperation of Fe7S8 with Fe3O4 and α-Fe not only improves the anti-oxidation ability of Fe7S8 coating but also broadens its band gap. By using Fe7S8/Fe3O4@Fe nanohybrids as photocatalysts, light irradiation accelerates the degradation of organic pollutants combined with enhanced mineralization efficiency. The Fe7S8/Fe3O4@Fe exhibits good performance when it is utilized to treat the influent from a municipal sewage treatment plant upon air aeration or under visible light and solar light irradiation.

Berbamine (BBM), a Natural STAT3 Inhibitor, Synergistically Enhances the Antigrowth and Proapoptotic Effects of Sorafenib on Hepatocellular Carcinoma Cells.

Sorafenib (SORA), a multi kinase inhibitor, is the standard first-line targeted therapy approved by the Food and Drug Administration for advanced hepatocellular carcinoma (HCC). However, emerging evidence from clinical practice indicates that SORA alone has only moderate antitumor effects and could not completely inhibit the progression of the disease. Therefore, it is very necessary and urgent to develop novel combination therapy to improve the clinical outcomes of SORA. The pharmacological study on the chemosensitizing effects of natural products has become a hotspot in recent years, which is commonly thought to be a potential way to improve the effectiveness of drugs in clinical use. Berbamine (BBM) has potential sensitizing effects in multiple chemotherapies and target therapy. However, it remains unclarified whether the combination of BBM and SORA as a treatment could exert a synergistic effect on HCC cell lines. In this study, we first investigated whether BBM can increase the sensitivity of HCC cell lines to SORA. The results revealed that the combination of BBM and SORA could synergistically inhibit the growth of two HCC cell lines and promoted their apoptosis. Mechanistically, our results showed that BBM exerted a dose-dependent inhibitory effect on the basal and IL-6-induced STAT3 activation of HCC cell lines. In addition, the combined treatment of BBM and SORA synergistically suppressed STAT3 phosphorylation at Tyr705 and knockdown of STAT3 abolished the sensitization effect of BBM, indicating that BBM's sensitization effect is mainly mediated by its inhibition of STAT3. These findings identify a new type of natural STAT3 inhibitor and provide a novel approach to the enhancement of SORA efficacy by blocking the activation of STAT3.

Proteus syndrome of the foot: A case report and literature review.

Proteus syndrome (PS) is an extremely rare and sporadic disorder characterized by asymmetric and/or disproportionate overgrowth of limbs, hamartomas, and vascular malformations. The onset of overgrowth usually involves the skin, bone, fat, and other connective tissues in a patchy or mosaic pattern. Partial gigantism of the affected limb or digit is a pathognomonic sign of PS. Thus far, only a few cases of PS have been recorded in the literature. In the present report, a case of PS in a 35-year old woman with classic cerebriform plantar hyperplasia and macrodactyly of the left foot was documented. The clinical and molecular characteristics and differential diagnosis of PS are also discussed in this report.

Foxo3 Promotes the Differentiation and Function of Follicular Helper T Cells.

Follicular helper T cells (Tfhs) are essential for germinal center (GC) B cell maturation and antibody development. However, the intrinsic mechanisms that regulate Tfh differentiation are largely unknown. Here, we demonstrate that the frequencies of Tfhs and GC B cells, as well as interleukin-21 (IL-21) and anti-ovalbumin (OVA) antibodies, are markedly decreased in forkhead box O3 (Foxo3) knockout mice immunized with OVA. Using mixed bone marrow chimeras and lymphocyte-repopulated Rag1-/- mice proves that wild-type (WT), but not Foxo3-deficient T cells provoke GC B cell maturation and antibody production. Deficiency of Foxo3 inhibits inducible T cell co-stimulator (ICOS)-induced Tfh differentiation. Chromatin immunoprecipitation assay results suggest that Foxo3 is able to bind to the IL-21 promoter and regulate IL-21 secretion. In conclusion, our study unveils a critical role of Foxo3 in the regulation of Tfh differentiation and IL-21 production. Modulating Foxo3 activity may be beneficial for enhancing or preventing antibody-mediated immune responses.

Comparative Effectiveness of Radiofrequency Ablation, Surgical Resection and Transplantation for Early Hepatocellular Carcinoma by Cancer Risk Groups: Results of Propensity Score-Weighted Analysis.

PURPOSE: Controversies exist for which treatment is optimal for early hepatocellular carcinoma (HCC): radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). We compared outcomes between treatments as first-line therapy for HCC patients measuring up to 5 cm or different cancer risk groups. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was retrieved for HCC patients treated with RFA, SR, or LT between 2004 and 2015. The effects of three treatments were compared using propensity score, inverse probability of treatment weights adjustment, and instrumental variable analysis for overall survival (OS) and competing risks regression models for disease-specific survival (DSS). We also evaluated whether the effect of treatments varied according to baseline clinical characteristics by locally weighted regression method. RESULTS: Of 7664 patients, RFA and SR yielded worse OS (HR 1.67, CI 1.43-1.70, P<0.001; HR 1.43, CI 1.40-1.67, P<0.001) and DSS (HR 2.00, CI 1.10-3.30, P<0.011; HR 2.50, CI 2.00-3.30, P<0.001) than LT. In patients with small tumors, SR may confer more survival benefits than RFA (HR>1) for different tumor sizes measuring up to 5 cm and may be an appropriate first-line treatment. Additionally, RFA has more survival benefits compared with SR (HR 0.83, CI 0.53-1.25) for those patients with low tumor risk and good general health condition (without any prognostic risk factors). However, those patients with a predicted 5-year overall mortality risk >30% seem to benefit more for SR than RFA. CONCLUSION: Due to a shortage of donors, RFA and SR can be applied as either primary management of HCC or as a bridging therapy for LT. Furthermore, SR is an effective option for patients with different HCC tumor size. However, RFA could achieve comparable survival benefits with SR for patients without any risk factors.

Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel.

Despite improvements in the prognosis of osteosarcoma patients, chemotherapy fails in a considerable number of cases due to drug resistance. The development of novel agents may enhance chemosensitivity. This study explored the anticancer function of polydatin and its ability-in combination with paclitaxel-to overcome drug resistance in human osteosarcoma U-2OS and MG-63 cell lines. A cell proliferation assay (celll counting kit-8), a cell-cycle assay, an apoptosis assay (annexin V-fluorescein isothiocyanate/propidium iodide), and a cell migration assay (Transwell) were used to analyze cell activity. Western blot analysis and quantitative reverse-transcription polymerase chain reaction were performed to examine function-related mRNA and protein levels. Treatment with polydatin suppressed cell growth and migration in both cell lines. Moreover, polydatin induced cell apoptosis in both parental and paclitaxel-resistant cells, and cell-cycle arrest in the S phase. Furthermore, it altered the expression of various proteins associated with cell growth (Ki67, p21, cyclin A, cyclin E, and cyclin-dependent kinase 2), migration (matrix metalloproteinase-2 [MMP-2], MMP-9, and tissue inhibitor of metalloproteinase-1), apoptosis (poly[ADP-ribose] polymerase 1 and caspase 3), and drug resistance (p-glycoprotein 1, lung resistance-related protein 1, growth arrest and DNA damage-45α, glutathione S-transferase π, and heat shock protein 27) in paclitaxel-resistant osteosarcoma cells. Cells transfected with myr-Akt caused obvious upregulation and activation of Akt, which were significantly attenuated via polydatin treatment. In conclusion, polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel.

The safety and efficacy of daylight photodynamic therapy in the treatment of actinic keratoses: a systematic review and meta-analysis.

Daylight photodynamic therapy (DLPDT) is a novel therapeutic approach for actinic keratoses (AKs). This study aimed to evaluate the safety and efficacy of DLPDT in treating patients with AKs as compared to conventional photodynamic therapy (CPDT). PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for relevant randomized controlled trials (RCTs) published before November 2017, based on the following search terms: "solar keratoses", "actinic keratoses", "photodynamic therapy", "daylight photodynamic therapy", "conventional photodynamic therapy", and "randomized". The complete response rate, patient satisfaction, and patient-reported pain after intervention with DLPDT or CPDT were primarily measured. Sensitivity analysis was conducted to determine the reliability of results. Begg's and Egger's tests were used to assess the likelihood of publication bias. Eight RCTs, comprising a total of 424 patients with AKs treated with DLPDT or CPDT, were included. No significant difference was found between the lesion response rate and the mean lesion response in a comparison of DLPDT and CPDT treatments. Generally, DLPDT was associated with higher patient satisfaction than CPDT. The patients who underwent DLPDT experienced less pain than those who underwent CPDT. Most of our results were of high stability and low sensitivity. Meanwhile, no statistical evidence of publication bias among studies was found under all comparisons. In conclusion, DLPDT is a safe and effective therapy, which could help in selecting the most appropriate therapeutic method for treating AKs and in guiding physicians to optimize treatment strategies.

Highly dispersed core-shell iron nanoparticles decorating onto graphene nanosheets for superior Zn(II) wastewater treatment.

This study reports the preparation of highly dispersed nanoscale zerovalent iron (nZVI) with core-shell structure decorated onto graphene nanosheets (Gr-NS) to form nZVI-Gr-NS composite. Meanwhile, its excellent performance for concentrated Zn(II) wastewater treatment is also studied. The adsorption of Zn(II) onto nZVI-Gr-NS is well simulated by the pseudo-second-order model, which indicates the adsorption is the rate-controlling step. Moreover, the adsorption isotherms of Zn(II) on the nZVI-Gr-NS can fit well with the Langmuir model. The negative thermodynamic parameters (△GƟ, △HƟ, △SƟ) calculated from the temperature-dependent isotherms indicate that the sorption reaction of Zn(II) is an exothermic and spontaneous process. The high saturation magnetization (37.4 emu g-1) of the nZVI-Gr-NS makes separation of nZVI-Gr-NS-bound Zn(II) easily and quickly from aqueous solution. Most importantly, nZVI-Gr-NS composites not only remove Zn(II) but also spontaneously remove As, Se, and Cu ions from real smelting wastewater samples. This study provides a good solution for heavy metal removal in real wastewater.

DNM1L, a key prognostic predictor for gastric adenocarcinoma, is involved in cell proliferation, invasion, and apoptosis.

Dynamin-1-like protein (DNM1L) encodes a member of the dynamin superfamily of GTPases. It mediates mitochondrial and peroxisomal division and is involved in the regulation of apoptosis. However, its role in gastric cancer remains unclear. MKN-45 gastric cancer cells were transfected with short hairpin RNA (shRNA) to suppress DNM1L expression. MTT, flow cytometry, and Transwell assays were used to detect the changes in cell proliferation, apoptosis, and invasion, respectively. Immunohistochemistry was used to detect DNM1L expression in gastric adenocarcinoma specimens, and the association of DNM1L expression with clinicopathological features and prognosis was analyzed. After the suppression of endogenous DNM1L expression in MKN-45 cells with shRNA, cell proliferation and invasion rates were significantly reduced, whereas apoptosis was significantly increased (all P<0.01). The expression of DNM1L was significantly higher in gastric adenocarcinoma specimens compared with that in pericarcinoma tissues (P<0.001). The expression of DNM1L increased with increasing infiltration depth, lymphatic metastasis, and higher tumor node metastasis stage (P<0.05). The expression of DNM1L associated negatively with prognosis (P<0.01). DNM1L plays a critical role in the proliferation, invasion and apoptosis of human gastric adenocarcinoma. DNM1L expression has prognostic significance for the survival of patients with gastric adenocarcinoma.

Graft survival rate of deep anterior lamellar keratoplasty for keratoconus: A meta-analysis.

BACKGROUND: Deep anterior lamellar keratoplasty (DALK) is an optional treatment for patients with keratoconus, and the associated graft survival rate varies. Herein, we aimed to explore the graft survival rate of DALK in patients with keratoconus. METHODS: PubMed, Web of Science, and ProQuest databases were searched to retrieve the related articles. General data, clinical characters, and graft survival rates were obtained directly from the included studies and analyzed by meta-analysis. RESULTS: A total of 12 articles were included. The merged 1-, 3-, and 5-year graft survival rates were 100% (99.9-100%, P < .001), 92.9% (89.8-95.9%, P < .001), and 90.4% (86.0-0.948%, P < .001), respectively. Lower heterogeneity was shown in each subgroup that was divided neither according to the sample number nor number of surgeons. CONCLUSION: The survival rate slightly decreases year by year, but the overall trend seems relatively stable. Ensuring that all DALK procedures are performed by a single surgeon might be helpful to improve the graft survival rate after surgery.

NGF and PI3K/Akt signaling participate in the ventral motor neuronal protection of curcumin in sciatic nerve injury rat models.

OBJECTIVE: It has been reported that sciatic nerve injury (SNI) leads to degeneration, damage, and apoptosis of motor neurons. Nerve growth factor (NGF) plays a pivotal role in regeneration and reestablishment of neuronal function via activating PI3K/Akt survival signaling pathways. Curcumin owns neuroprotective effect following brain injury. In the present study, we attempt to investigate underlying mechanism of neuroprotective effect of curcumin through elucidating its correlation with NGF and PI3K/Akt signaling pathways in vitro and in vivo. METHODS: PC-12 cells were exposed H2O2 in order to induce neuron cell injury and cells were then treated with curcumin. Caspase-3, NGF level and Akt phosphorylation were determined using flow cytometry and western blotting. Then, cells were treated with NGF specific siRNA followed by measurement of apoptosis, NGF and Akt phosphorylation levels. In animal model, rats were subjected to SNI and then randomly designated into four different groups: curcumin, curcumin + LY294002, curcumin + NGF shRNA, and negative controls and 12 rats in each group (n = 12). After four weeks of continuous treatment, tissue samples were obtained and subjected to TUNEL, NeuN double staining and western blotting. RESULTS: Curcumin significantly reduced the number of apoptotic cells induced by H2O2 and this effect was associated with upregulation of TrkA, Akt and downregulation of p17. ProNGF level was significantly decreased while mature NGF level was increased with curcumin treatment. When NGF was suppressed, anti-apoptotic effect of curcumin was attenuated. In addition, inhibition of PI3K/Akt results in increased apoptotic rate compared to vehicles following curcumin treatment which was reflected by decreased p17, Ki67, and cyclin D1. Suppression of NGF and inhibition of PI3K led to increased neuron cell death through increasing proNGF and decreasing mNGF, Akt, TrkA, p75NTR, and p17. CONCLUSION: Our findings revealed that curcumin exerts its protective effect against injured neurons through stimulating NGF release which further activates TrkA and PI3K/Akt cell survival signaling.

Genipin-Cross-Linked Chitosan Nerve Conduits Containing TNF-α Inhibitors for Peripheral Nerve Repair.

Tissue engineered nerve grafts (TENGs) are considered a promising alternative to autologous nerve grafting, which is considered the "gold standard" clinical strategy for peripheral nerve repair. Here, we immobilized tumor necrosis factor-α (TNF-α) inhibitors onto a nerve conduit, which was introduced into a chitosan (CS) matrix scaffold utilizing genipin (GP) as the crosslinking agent, to fabricate CS-GP-TNF-α inhibitor nerve conduits. The in vitro release kinetics of TNF-α inhibitors from the CS-GP-TNF-α inhibitor nerve conduits were investigated using high-performance liquid chromatography. The in vivo continuous release profile of the TNF-α inhibitors released from the CS-GP-TNF-α inhibitor nerve conduits was measured using an enzyme-linked immunosorbent assay over 14 days. We found that the amount of TNF-α inhibitors released decreased with time after the bridging of the sciatic nerve defects in rats. Moreover, 4 and 12 weeks after surgery, histological analyses and functional evaluations were carried out to assess the influence of the TENG on regeneration. Immunochemistry performed 4 weeks after grafting to assess early regeneration outcomes revealed that the TENG strikingly promoted axonal outgrowth. Twelve weeks after grafting, the TENG accelerated myelin sheath formation, as well as functional restoration. In general, the regenerative outcomes following TENG more closely paralleled findings observed with autologous grafting than the use of the CS matrix scaffold. Collectively, our data indicate that the CS-GP-TNF-α inhibitor nerve conduits comprised an elaborate system for sustained release of TNF-α inhibitors in vitro, while studies in vivo demonstrated that the TENG could accelerate regenerating axonal outgrowth and functional restoration. The introduction of CS-GP-TNF-α-inhibitor nerve conduits into a scaffold may contribute to an efficient and adaptive immune microenvironment that can be used to facilitate peripheral nerve repair.

Association between the rs112735431 polymorphism of the RNF213 gene and moyamoya disease: A case-control study and meta-analysis.

Ring finger protein 213 (RNF213) gene polymorphisms are thought to be significant in the etiology and pathogenesis of moyamoya disease (MMD). Due to the rarity of MMD patients, their ethnic diversity, and the use of varying methodologies, studies of the association between these polymorphisms and MMD have not been repeatable. This lack of reproducibility affects the strength of the conclusions drawn from their results. We conducted the present case-control study and meta-analysis to provide more precise estimates of the association between the rs112735431 (c.14576G>A) polymorphism and the risk of MMD. A total of 81 MMD patients and 100 healthy controls were enrolled in our case-control study. The RNF213 rs112735431 (c.14576G>A) polymorphism was genotyped using Sanger sequencing after amplification with polymerase chain reaction (PCR). The genetic algorithm (GA) genotype and A allele frequencies of RNF213 rs112735431 (c.14576G>A) (odds ratio, OR=7.10, 95% confidence interval, CI=1.51-33.43, p=0.006; OR=9.37, 95% CI=2.10-41.84, p<0.001, respectively) were significantly higher in the MMD group than those in the control group. In our meta-analysis, we assessed a total of eight case-control studies, including 985 patients and 2335 controls. Pooled ORs indicated a significant association between the presence of the rs112735431 (c.14576G>A) polymorphism and MMD risk (dominant model: OR=74.55, 95% CI=35.86-154.98, p<0.00001). Subgroup analysis based on country and sensitivity analysis verified these results. Our case-control study and meta-analysis both provide evidence of an association between the rs112735431(c.14576G>A) polymorphism in the RNF213 gene and MMD risk.

Synthesis and neuroprotective effects of the fluorine substituted salidroside analogues in the PC12 cell model exposed to hypoglycemia and serum limitation.

Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L., a traditional Chinese medicinal plant, which elicits neuroprotective effects in the treatment of ischemic stroke. In an attempt to improve its neuroprotective effects, fluorine substituted Sal analogues were synthesized and their neuroprotective activities against the hypoglycemia and serum limitation induced cell injury in differentiated PC12 cells were evaluated. The target compounds displayed strong protective effects on the cell viability against the damage caused by hypoglycemia and serum limitation, especially for D1, which had a great potency superior to Sal and efficiently inhibited hypoglycemia and serum limitation induced cell nuclear morphologic changes and the increased apoptotic rate in a dose-dependent manner. These new findings may provide potentially important information for further development of Sal analogues and lay the basis for further studies on the cerebral ischemic stroke and neurodegenerative diseases for human clinical treatment.

Repairing rat sciatic nerve injury by a nerve-growth-factor-loaded, chitosan-based nerve conduit.

We have developed a nerve conduit made up of chitosan, on which nerve growth factor (NGF) was immobilized via genipin cross-linking. The nerve conduit was used to bridge a 10-mm-long sciatic nerve gap in rats. At 24 weeks after surgery, electrophysiological assessment, behavioral analysis, and histological examination were conducted to evaluate the outcomes of peripheral nerve repair. The nerve conduit allowed nerve reconstruction between two stumps and reinnervation of the target gastrocnemius muscle. For two groups of rats repaired respectively by the nerve conduit and autologous nerve graft, the density of regenerated axons was 3.55 ± 0.51 and 3.91 ± 0.14 (P = 0.712), and the cross-sectional area of target muscles was 1,159.68 ± 305.85 and 1,307.06 ± 301.25 (P = 0.922), respectively, without significant differences between the two groups. Our data suggest the feasibility of using chitosan-based, NGF-loaded nerve conduits for peripheral nerve repair.