Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Nanomaterials-Involved Tumor-Associated Macrophages' Reprogramming for Antitumor Therapy.

Tumor-associated macrophages (TAMs) play pivotal roles in tumor development. As primary contents of tumor environment (TME), TAMs secrete inflammation-related substances to regulate tumoral occurrence and development. There are two kinds of TAMs: the tumoricidal M1-like TAMs and protumoral M2-like TAMs. Reprogramming TAMs from immunosuppressive M2 to immunocompetent M1 phenotype is considered a feasible way to improve immunotherapeutic efficiency. Notably, nanomaterials show great potential for biomedical fields due to their controllable structures and properties. There are many types of nanomaterials that exhibit great regulatory activities for TAMs' reprogramming. In this review, the recent progress of nanomaterials-involved TAMs' reprogramming is comprehensively discussed. The various nanomaterials for TAMs' reprogramming and the reprogramming strategies are summarized and introduced. Additionally, the challenges and perspectives of TAMs' reprogramming for efficient therapy are discussed, aiming to provide inspiration for TAMs' regulator design and promote the development of TAMs-mediated immunotherapy.

"Multi-in-One" Yolk-Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions.

Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2 O2 ) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.

Metal-amplified sonodynamic therapy of Ti-based chitosan-polyvinyl alcohol hybrid hydrogel dressing against subcutaneous Staphylococcus aureus infection.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has received extensive attention in pathogen elimination for non-invasiveness and high spatial and temporal accuracy. Considering that hydrogel can provide a healing-friendly environment for wounds, in this work, hybrid hydrogels are constructed by embedding Ag doped TiO2 nanoparticles in chitosan-polyvinyl alcohol hydrogels for enhanced sonodynamic antibacterial therapy. With metal silver doped, TiO2 nanoparticles sonosensitivity is improved to generate more reactive oxygen species (ROS), which endows hybrid hydrogels with high-efficient antibacterial properties. In vivo results show that hybrid hydrogel dressing can prevent infection and promote wound closure within 2 days. The healing ratio excess 95 % with no pus produced at the end of treatment. The therapeutic mechanism was identified that heterojunction formed in Ag doped TiO2 facilitates the separation of charge carriers under US irradiation, leading to elevating ROS generation. The generated ROS promote hybrid hydrogels sonodynamic antibacterial therapeutic efficacy to thoroughly eliminate pathogen via disrupting bacterial cell membrane integrity, decreasing membrane fluidity and increasing membrane permeability. Besides, biofilm formation could be effectively inhibited. This work developed a hybrid hydrogel with amplified SDT effect for wound healing, which is expected to provide inspiration of hybrid hydrogels design and Ti-based nanomaterials sonosensitivity enhancement.

Recent strategies of carbon dot-based nanodrugs for enhanced emerging antitumor modalities.

Nanomaterial-based cancer therapy has recently emerged as a new therapeutic modality with the advantages of minimal invasiveness and negligible normal tissue toxicity over traditional cancer treatments. However, the complex microenvironment and self-protective mechanisms of tumors have suppressed the therapeutic effect of emerging antitumor modalities, which seriously hindered the transformation of these modalities to clinical settings. Due to the excellent biocompatibility, unique physicochemical properties and easy surface modification, carbon dots, as promising nanomaterials in the biomedical field, can effectively improve the therapeutic effect of emerging antitumor modalities as multifunctional nanoplatforms. In this review, the mechanism and limitations of emerging therapeutic modalities are described. Further, the recent advances related to carbon dot-based nanoplatforms in overcoming the therapeutic barriers of various emerging therapies are systematically summarized. Finally, the prospects and potential obstacles for the clinical translation of carbon dot-based nanoplatforms in tumor therapy are also discussed. This review is expected to provide a reference for nanomaterial design and its development for the efficacy enhancement of emerging therapeutic modalities.

AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy.

Nanocatalytic therapy (NCT) has made great achievements in tumor treatments due to its remarkable enzyme-like activities and high specificity. Nevertheless, the limited types of nanozymes and undesirable tumor microenvironments (TME) greatly weaken the therapeutic efficiency. Developing a combination therapy integrating NCT and other strategies is of great significance for optimal treatment outcomes. Herein, a AuPt-loaded Cu-doped polydopamine nanocomposite (AuPt@Cu-PDA) with multiple enzyme-like activities was rationally designed, which integrated photothermal therapy (PTT) and NCT. The peroxidase (POD)-like activity of AuPt@Cu-PDA can catalyze hydrogen peroxide (H2O2) into ·OH, and the catalase (CAT)-mimic activity can decompose H2O2 into O2 to alleviate hypoxia of TME, and O2 can be further converted into toxic ·O2- by its oxidase (OXD)-mimic activity. In addition, Cu2+ in AuPt@Cu-PDA can effectively consume GSH overexpressed in tumor cells. The boosting of reactive oxygen species (ROS) and glutathione (GSH) depletion can lead to severe oxidative stress, which can be enhanced by its excellent photothermal performance. Most importantly, the accumulation of Cu2+ can disrupt copper homeostasis, promote the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), disrupt the mitochondrial tricarboxylic acid (TCA) cycle, and finally result in cuproptosis. Collectively, photothermal and photoacoustic imaging (PTI/PAI)-guided cuproptosis-enhanced NCT/PTT can be achieved. This work may expand the application of nanozymes in synergistic therapy and provide new insights into cuproptosis-related therapeutic strategies.

Inhibition mechanism of human insulin fibrillation by Bodipy carbon polymer dots and photothermal defibrillation effect of Bodipy carbon polymer dots modified by ThT.

Fibrillation process of human insulin (HI) is closely related to type 2 diabetes (T2D). In the present work, Carbon Polymer Dots (CPDs) was synthesized by Bodipy to control the process of insulin fibrillation. The inhibition process of insulin fibrillation with the existence of CPDs was completed investigated. The hydrophobic interaction of CPDs and insulin was used to inhibit the change of insulin's secondary structure in the lag phase and growth period. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CPDs were used to explore the kinetics of insulin fibrillation and regulation process by CPDs. Isothermal titration calorimetry (ITC) was applied to explore the regulatory mechanism by CPDs at all stages of the insulin fibrillation process. ThT was used to complete the chemical modification of CPDs by Friedel-Crafts alkylation, which made the CPDs maintain the characteristics of photothermal effect and also obtain the ability to bind specifically to the fibers. Finally, the process of defibrillation of human insulin fibers under the Near-infrared light's irradiation was realized. In this work, we clarified the mechanism of the regulation process by Bodipy CPDs and made CPDs able to defibrillate the insulin fibers by chemical modification.

MXenes Functionalized with Macrocyclic Hosts: From Molecular Design to Applications.

Two-dimensional (2D) MXene has aroused wide attention for its excellent physical and chemical properties. The interlayer engineering formed by layer-by-layer stacking of MXene nanosheets can be employed for molecular sieving and water purification by incorporating specific groups onto the exterior surface of MXene. Macrocyclic hosts exhibiting unique structural features and recognition ability can construct smart devices for external stimuli with reversible features between macrocycles and guests. On that basis, macrocyclic hosts can be anchored to MXene to provide numerous insights into their compositions and intercalation states. In this review, the MXene prepared based on macrocyclic hosts from molecular design to applications is highlighted. Various MXenes functionalized with macrocyclic hosts are empowered in functional membrane (including water purification, organic solvent nanofiltration, and electromagnetic shielding), photocatalysis, sensing, and adsorption (interactions with specific guest). Hopefully, this review can bring new inspiration to the design of multifunctional MXene-based materials and improving its practical applications.

Core-Shell Polydopamine/Cu Nanometer Rods Efficiently Deactivate Microbes by Mimicking Chloride-Activated Peroxidases.

Cu-modified nanoparticles have been designed to mimic peroxidase, and their potent antibacterial and anti-biofilm abilities have been widely investigated. In this study, novel core-shell polydopamine (PDA)/Cu4(OH)6SO4 crystal (PDA/Cu) nanometer rods were prepared. The PDA/Cu nanometer rods show similar kinetic behaviors to chloride-activated peroxidases, exhibit excellent photothermal properties, and are sensitive to the concentrations of pH values and the substrate (i.e., H2O2). PDA/Cu nanometer rods could adhere to the bacteria and catalyze hydrogen peroxide (H2O2) to generate more reactive hydroxy radicals (•OH) against Staphylococcus aureus and Escherichia coli, Furthermore, PDA/Cu nanometer rods show enhanced catalytic and photothermal synergistic antibacterial activity. This work provides a simple, inexpensive, and effective strategy for antibacterial applications.

Zn-doped Cu2S quantum dots as new high-efficiency inhibitors against human insulin fibrillation based on specific electrostatic interaction with oligomers.

Inhibition of protein fibrillation process with nanomaterials is a promising strategy to combat neurodegenerative diseases. Copper-based nanomaterials have been seldom utilized in fibrillation inhibiting research due to Copper ions are generally considered as accelerators of fibrosis. Here, we proposed ultra-small Zn doped Cu2S (Zn:Cu2S) QDs as inhibitors of human insulin (HI) fibrosis. ThT, DLS, CD and TEM confirm that Zn:Cu2S QDs effectively inhibited insulin fibrosis in a dose-dependent manner with lag phase time extended (beyond 13-time by Zn:Cu2S QDs of 1 mg·mL-1), final fibril formation and the conversion from α-helix to ß-sheet reduced. Additionally, thermodynamics analyzed results reveal that the HI fluorescence quenching process is static quenching dominated, and the Zn:Cu2S QDs inhibit HI fibrosis mainly through specific electrostatic interaction with oligomers. The positively charged amino acid residues of oligomers bind to the negatively charged Zn:Cu2S QDs, which prevents the self-assembly of the oligomers from growing into mature fibers to enhance the stability of the protein. Unlike free Copper ions, the as-prepared QDs show an excellent inhibition in HI fibrillation, breaking through the bottleneck of copper-based materials in inhibiting protein fibrosis and providing a potential strategy to inhibit protein fibrosis in-situ by biosynthesizing copper-based fibrosis inhibitors.

Near-infrared Zn-doped Cu2S quantum dots: an ultrasmall theranostic agent for tumor cell imaging and chemodynamic therapy.

Theranostic agents that integrated chemodynamic therapy (CDT) and imaging functions have great potential application in personalized cancer therapy. However, most theranostic agents were fabricated by chemically coupling two or more independent functional units with diagnostic or therapeutic capabilities, and therefore have a large size. To date, one-step synthesis of unmodified ultrasmall quantum dots (QDs) integrating CDT and fluorescence imaging capabilities remains a challenge. Herein, we reported a simple one-step synthesis method of ultrasmall (2.46 nm) Zn-doped Cu2S (Zn:Cu2S) QDs with inherent properties of both high CDT activity and near-infrared fluorescence imaging capability. The fluorescence of Cu2S QDs was significantly enhanced approximately tenfold after Zn doping due to the compensation of defects. In vitro and in vivo experiments demonstrated that the Zn:Cu2S QDs could specifically and significantly inhibit the cancer cell growth (inhibition rate exceeded 65%) without damaging the normal cells. Furthermore, the CDT mechanism study suggested that a Fenton-like reaction occurred after the Zn:Cu2S QDs entered the tumor cells, inducing apoptosis via the mitochondrial signaling pathway, and activating the production of reactive oxygen species (ROS) and autophagy to selectively eliminate tumor cells to achieve CDT. This work proposed a simple one-step synthesis of unmodified ultrasmall QDs with fluorescence imaging and CDT, which provides a promising strategy for QDs to act as multi-functional theranostic agents.

Molecular Mechanisms of the Ultra-Strong Inhibition Effect of Oxidized Carbon Dots on Human Insulin Fibrillation.

Amyloid fibrillation of protein is associated with a great variety of pathologic conditions. The aggregation of protein is a complicated process with multisteps, whereas most of the inhibitors with elaborately designed structures can show an inhibition effect only on the nucleation stages of protein fibrillation. Herein, oxidized carbon dots (CDs) were achieved to study the relationship between the surface properties of CDs and their inhibition effect on human insulin (HI) fibrillation. More oxygen-containing function groups can be obtained after oxidation reaction of CDs, such as -OH and -COOH. The results show that 10-1 CDs (the mass ratios of CD/KMnO4 is 10:1), with the highest carboxyl group content, possess the best inhibition ability. All the nucleation, growth, and final phases can be retarded by 10-1 CDs, which have been studied in detail by fluorescence spectra. However, CDs without oxidation can show only a weak inhibition effect on the nucleation stage. The 10-1 CDs is demonstrated to binding with HI monomers much stronger than that of CDs by isothermal titration calorimetry (ITC). Moreover, molecular dynamics simulations (MD) studies indicate that CDs with more carboxyl groups can show stronger affinities with native or unfolded HI monomers, which may be mainly derived from the active binding sites of histidine residues (His5 and His10) on B-chain through electrostatic interaction. Because the unfolding of B-chain in HI is prior to that of A-chain in our MD simulations, the later aggregation of HI can be inhibited effectively by the stronger binding forces between 10 and 1 CDs and the B-chain of HI.

An in vivo anti-tumor effect of eckol from marine brown algae by improving the immune response.

The anti-cancer activities of brown algae and some active extracts or components from brown algae have been demonstrated. But the anti-tumor activities of eckol, a new natural phlorotannin derived from marine brown algae, are poorly understood. In order to investigate the in vivo anti-tumor effect and its potential mechanisms of eckol in a sarcoma 180 (S180) xenograft-bearing animal model, S180 xenograft-bearing mice were randomly divided into 4 groups: model control, and eckol low-dose (0.25 mg kg-1), middle-dose (0.5 mg kg-1) and high-dose (1.0 mg kg-1) groups. After eckol administration, the tumor inhibition, tumor tissue histology, thymus index and spleen index were measured. The apoptotic tumor cells were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The protein expression levels of cleaved Caspase-3 and Caspase-9 (two key apoptotic proteins), Bcl-2 and Bax (two key anti-apoptosis-related genes), as well as epidermal growth factor receptor (EGFR, a well-known cell proliferation-stimulating molecule in tumorigenesis) and p-EGFR in tumor tissues were determined by western blot. A carbon particle clearance test, measurement of serum cytokine levels, a splenic T lymphocyte proliferation test, and T lymphocyte subpopulation analysis were used to evaluate the effect of eckol on the immune function of tumor-bearing mice. Moreover, CD11c+-dendritic cell (DC) infiltration in tumor tissues was detected by immunohistochemistry, and the surface molecules on bone marrow-derived DCs were analyzed using flow cytometry. The pro-apoptosis and anti-proliferation activities of eckol were manifested by the increased TUNEL-positive apoptotic cells, the upregulated Caspase-3 and Caspase-9 expression, and the downregulated expression of Bcl-2, Bax, EGFR and p-EGFR in eckol-treated transplanted S180 tumors. Most importantly, eckol stimulated the mononuclear phagocytic system, recruited and activated DCs, promoted the tumor-specific Th1 responses, increased the CD4+/CD8+ T lymphocyte ratio, and enhanced cytotoxic T lymphocyte responses in the eckol-treated animals, suggesting its potent stimulatory property on innate and adaptive immune responses. This study suggested that eckol might act as a functional food constituent derived from marine brown algae with a potential in vivo anti-tumor effect achieved by improving the immune response.

High-Oxygen-Content Carbon Dots as a High-Efficiency Inhibitor of Human Insulin Aggregation.

Neurodegenerative diseases consist of Alzheimer's disease and type 2 diabetes which pose serious health effects. Carbon dots are widely used in the treatment of these types of diseases with their excellent biocompatibility and low toxicity. Herein, we use l- or d-cysteine to synthesize nontoxic high-oxygen carbon dots with a size around 3 nm and full of highly oxygenic functional groups. Through a ThT fluorescence assay, far-UV CD spectroscopy, and TEM, we find that carbon dots (CDs) can inhibit the nucleation process and elongate the lag phase by a large degree, and the higher-oxygen content one (d-CDs) exhibits a more significant inhibitory effect. When the dose of d-CDs reached 0.5 mg mL-1, it can impede the protofibril formation for nearly 1 week. Through the isothermal titration calorimetry (ITC) experiment, we obtain this result because d-CDs interact with the human insulin (HI) monomer (Ka1 = 2.46 × 104 L mol-1) stronger than l-CDs do (Ka2 = 1.62 × 103 L mol-1). More importantly, these two high-oxygen CDs still have a gorgeous inhibitory effect; even human insulin was nucleated, which has not been reported previously. This is because the association constant of fibril seeds interacting with d-CDs (Ka3 = 2.91 × 104 L mol-1) is large and competes against the interaction with the HI monomer so it can slow the fibrillation rate. Moreover, the interaction is mainly driven by electrostatic force. This is the first time results have been found of highly oxygenic CDs having a great inhibitory effect when they already have the growth sites and are illustrated by ITC experiments, which suggest further protein fibrillation inhibition.

Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study.

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.

[Effect of recombinant human erythropoietin on hepcidin mRNA expression in patients with multiple myeloma].

This study was purposed to investigate the effect of multiple myeloma patients' sera on hepcidin mRNA expression of Hep-3b hepatoma cell line and effect of human interleukin-6 (IL-6) antibody or recombinant human erythropoietin (rhEPO) on hepcidin mRNA expression. The clinical information and serum of multiple myeloma patients were collected. Their sera of a final concentration of 10% were added into Hep-3b cell medium. The mRNA from Hep-3b cells was extracted, and hepcidin mRNA expression was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A final concentration of 10 ng/ml human IL-6 antibody and 2 U/ml rhEPO were added into the medium respectively. The results showed that the sera of untreated multiple myeloma patients elevated hepcidin mRNA expression of Hep-3b cells, compared with healthy controls and iron deficiency anemia patients. This effect was fully neutralized by human IL-6 antibody or rhEPO. The hemoglobin (Hb) level was stable during the follow up of regularly treated multiple myeloma patients and the effect of MM patient serum on Hep-3b cell hepcidin mRNA expression was reduced. It is concluded that the hepcidin mRNA expression of Hep-3b cell can be increased by untreated multiple myeloma patient serum. This promotive effect can be antagonised by IL-6, which suggests that IL-6 may be possible to elevate expression level of hepcidin in Hep-3b cells and results in anemia of chronic disease (ACD). The above mentioned promotive effects also can be suppressed by rhEPO, which indicates that the rhEPO may possess curative effect for ACD disease. During short-term follow-up of treated patients with multiple myeloma the Hb level is stable, the influence of patients serum on hepcidin mRNA of Hep-3b cells decreases, which shows the stabilization of disease and amelioration of ACD patient status.

[Therapeutic mechanisms of interferon-beta and intravenous immunoglobulin for experimental peripheral neuropathy].

OBJECTIVE: To explore the therapeutic mechanisms of interferon-beta (IFN-beta) and intravenous immunoglobulin (IVIG) for experimental peripheral neuropathy induced by Campilobacter jejuni (Cj) lipopolysaccharide (LPS). METHOD: Forty healthy Wistar rats weighing 205 - 230 g were divided into IFN-beta, IVIG, IFN-beta plus IVIG and control groups. After the immune neuropathy was induced in the rats by Cj LPS, IFN-beta (1.3 microg/kg) was given by subcutaneous injection to the rats every other day for 6 weeks; IVIG [400 mg/(kg x d)] was given to the rats for five days, every other week for two times and IFN-beta [1.3 microg/(kg x d)] and IVIG [400 mg/(kg x d)] were given to the rats on the same days. Meanwhile, the control group was given PBS. The sera were collected in the 2nd, 4th and 6th week after therapy, the titers of anti-GM(1) IgG, MMP-9 and TNF-alpha in sera of immunized rats were measured by ELISA; histological study of sciatic nerve was performed and IgG on sciatic nerve was detected by immunohistochemistry in the 6th week. RESULTS: (1) There were no significant differences in titers of anti-GM(1) IgG, MMP-9 and TNF-alpha among the 3 therapeutic groups and control group after therapy for 2 weeks (P > 0.05). (2) The titers of anti- GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta and IVIG group after therapy for 4 weeks (P > 0.01) and there were no significant differences in titers of antibody among the 3 therapeutic groups (P > 0.05); the titers of MMP-9 or TNF-alpha in the IFN-beta and IVIG group were lower than those of the IFN-beta group or the IVIG group (P < 0.05). (3) The titers of anti-GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta with IVIG group after therapy for 6 weeks (P > 0.01); the IFN-beta with IVIG group had much lower levels of all indexes than the IFN-beta group or the IVIG group (P < 0.01). CONCLUSION: IFN-beta and IVIG showed therapeutic effects on immune peripheral neuropathy through inhibiting the humoral and cellular immunity simultaneously in the peripheral neuropathy induced by CJ LPS, treatment with combined IFN-beta and IVIG was more effective.

[Study on the correlation of serum folate and red blood cell folate level with birth defects and unexplained recurrent pregnancy loss].

OBJECTIVE: To understand the correlation of lower serum folate, and red blood cell (RBC) folate level with birth defects including unexplained recurrent pregnancy loss, and to evaluate the role of RBC folate level as a suitable marker for folate supplement. METHODS: Two hundred and ninety-nine non-pregnant women at child-bearing age with a birth defect history were selected as birth defect group. The levels of serum and RBC folate, and serum vitamin B(12) were determined. By comparing with the group of non-pregnant women at child-bearing age without any birth defect history (control group), we evaluated the correlation between lower serum folate, RBC folate level and main kinds of birth defects including unexplained recurrent pregnancy loss. And the levels of serum and RBC folate of birth defect group were also determined and compared before and after oral folate intake (5 mg/d) for one month. RESULTS: The serum folate level of birth defect group was not different from the control group (17 - 26 vs 14 nmol/L, P > 0.05). The RBC folate level of birth defect group except the urinary defect was significantly lower compared with the control group (233 - 547 vs 689 nmol/L, P < 0.05). After the oral folate intake (5 mg/d), the serum folate level of unexplained recurrent pregnancy loss group and neural tube defects group were significantly increased than before [(22 +/- 9) vs (27 +/- 12) nmol/L, (19 +/- 10) vs (25 +/- 18) nmol/L; P < 0.05]. The RBC folate level of unexplained recurrent pregnancy loss group and congenital heart defect group were significantly increased than before [(374 +/- 275) vs (567 +/- 397) nmol/L, (322 +/- 205) vs (527 +/- 351) nmol/L, P < 0.05]. CONCLUSION: RBC folate level is more closely correlated than serum folate level with the incidence of main birth defect.