Increasing the Particle Size and Magnetic Property of Iron Oxide Nanoparticles through a Segregated Nucleation and Growth Process.

Iron oxide nanoparticles (IONs) with good water dispersibility were prepared by the thermal decomposition of iron acetylacetonate (Fe(acac)3) in the high-boiling organic solvent polyethylene glycol (PEG) using polyethyleneimine (PEI) as a modifier. The nucleation and growth processes of the crystals were separated during the reaction process by batch additions of the reaction material, which could inhibit the nucleation but maintain the crystal growth, and products with larger particle sizes and high saturation magnetization were obtained. The method of batch addition of the reactant prepared IONs with the largest particle size and the highest saturation magnetization compared with IONs reported using PEG as the reaction solvent. The IONs prepared by this method also retained good water dispersibility. Therefore, these IONs are potentially suitable for the magnetic separation of cells, proteins, or nucleic acids when large magnetic responses are needed.

Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway.

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.

Efficacy and Safety of Type III Collagen Lyophilized Fibers Using Mid-to-Deep Dermal Facial Injections for the Correction of Dynamic Facial Wrinkles.

BACKGROUND: This study aimed to evaluate the therapeutic efficacy and safety of injecting Type III collagen lyophilized fibers into the mid-to-deep layers of the facial dermis to ameliorate dynamic facial wrinkles. METHODS: In this retrospective analysis, clinical data were collected from patients exhibiting dynamic facial wrinkles (encompassing frown lines, forehead lines, and crow's feet) with a wrinkle severity rating scale (WSRS) score of 3 or higher. In the control group, 75 participants received collagen implant injections into the mid-to-deep facial dermal layers, whereas 76 participants in the experimental group received injections of Type III collagen lyophilized fibers in similar layers. The study analyzed and compared clinical efficacy, WSRS score alterations, patient satisfaction, and safety profiles between the groups over the 30-day and 90-day treatment periods. RESULTS: At the 30-day mark, the therapeutic efficacy was not significantly different between the two groups (P > 0.05). However, at 90 days, the treatment efficacy in the experimental group surpassed that in the control group, showing a statistically significant difference (P < 0.05). After 30 days of treatment, the WSRS score improvement in the experimental group was significantly superior to that in the control group (P < 0.05). Conversely, at the 90-day mark, the results revealed no significant variation in WSRS score improvements between the two groups (P > 0.05). Regarding treatment satisfaction among researchers and participants post-30 and 90-day treatment in both groups, no statistically significant differences were observed (P > 0.05). Similarly, the incidence of adverse reactions between the groups was not statistically significant (P > 0.05). CONCLUSIONS: Injections of lyophilized type III collagen fibers into the mid-to-deep layers of the facial dermis have a definitive therapeutic effect on dynamic facial wrinkles. This treatment not only substantially diminishes wrinkle severity but also has a commendable safety profile. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A new step-wise surgical technique of knapsack-like uterine compression sutures for intractable postpartum hemorrhage in cesarean section.

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).

Stem cell-derived exosomes for traumatic spinal cord injury: a systematic review and network meta-analysis based on a rat model.

BACKGROUND AIMS: Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear. METHODS: The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators. RESULTS: A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention. CONCLUSIONS: The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells.

Predictive models for starting dose of gonadotropin in controlled ovarian hyperstimulation: review and progress update.

Controlled ovarian hyperstimulation (COH) is an essential for in vitro fertilization-embryo transfer (IVF-ET) and an important aspect of assisted reproductive technology (ART). Individual starting doses of gonadotropin (Gn) is a critical decision in the process of COH. It has a crucial impact on the number of retrieved oocytes, the cancelling rate of ART cycles, and complications such as ovarian hyperstimulation syndrome (OHSS), as well as pregnancy outcomes. How to make clinical team more standardized and accurate in determining the starting dose of Gn is an important issue in reproductive medicine. In the past 20 years, research teams worldwide have explored prediction models for Gn starting doses. With the integration of artificial intelligence (AI) and deep learning, it is hoped that there will be more suitable predictive model for Gn starting dose in the future.

Separator Engineering Based on Cl-Terminated MXene Ink: Enhancing Li+ Diffusion Kinetics with a Highly Stable Double-Halide Solid Electrolyte Interphase.

Separator engineering is a promising route to designing advanced lithium (Li) metal anodes for high-performance Li metal batteries (LMBs). Conventional separators are incapable of regulating the Li+ diffusion across the solid electrolyte interphase (SEI), leading to severe dendritic deposition. To address this issue, a polypropylene (PP) separator modified by spray coating the Cl-terminated titanium carbonitride MXene ink is designed (PP@Ti3CNCl2). The lithiophilic MXene provides excellent electrolyte wettability and low Li+ diffusion barriers, finally enhancing the Li+ diffusion kinetics of excessively stable SEI. The X-ray photoelectron spectroscopy depth profiling as well as cryo-transmission electron microscopy reveals that a gradient SEI hierarchy with evenly distributed LiF and LiCl is spontaneously formed during the electrochemical process. As a consequence, PP@Ti3CNCl2 delivers a high Coulombic efficiency (99.15%) coupled with a prolonged lifespan of over 5500 h in half cells and 3100 cycles at 2 C in full cells. This work offers an effective strategy for constructing dendrite-free and Li+ permeable interfaces toward high-energy-density LMBs.

Bibliometric analysis of stem cells for spinal cord injury: current status and emerging frontiers.

Background: This study aimed to conduct a bibliometric analysis of the literature on stem cell therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field. Methods: We searched the Web of Science Core Collection database using relevant keywords ("stem cells" and "spinal cord injury") and retrieved the published literature between 2000 and 2022. Data such as journal title, author information, institutional affiliation, country, and keywords were extracted. Afterwards, we performed bibliometric analysis of the retrieved data using Bibliometrix, VOSviewer, and CiteSpace. Results: A total of 5375 articles related to stem cell therapy for spinal cord injury were retrieved, and both the annual publication volume and the cumulative publication volume showed an upward trend. neural regeneration research was the journal with the most publications and the fastest cumulative publication growth (162 articles), Okano Hideyuki was the author with the highest number of publications and citations (114 articles), Sun Yat-sen University was the institution with the highest number of publications (420 articles), and China was the country with the highest number of publications (5357 articles). However, different authors, institutions, and countries need to enhance their cooperation in order to promote the generation of significant academic achievements. Current research in this field has focused on stem cell transplantation, neural regeneration, motor function recovery, exosomes, and tissue engineering. Meanwhile, future research directions are primarily concerned with the molecular mechanisms, safety, clinical trials, exosomes, scaffolds, hydrogels, and inflammatory responses of stem cell therapy for spinal cord injuries. Conclusion: In summary, this study provided a comprehensive analysis of the current research status and frontiers of stem cell therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of stem cell therapy in this field.

10th antibody industrial symposium: new developments in antibody and adoptive cell therapies.

The annual "Antibody Industrial Symposium", co-organized by LabEx MAbImprove and MabDesign, held its 10th anniversary edition in Montpellier, France, on June 28-29, 2022. The meeting focused on new results and concepts in antibody engineering (naked, mono- or multi-specific, conjugated to drugs or radioelements) and also on new cell-based therapies, such as chimeric antigenic receptor (CAR)-T cells. The symposium, which brought together scientists from academia and industry, also addressed issues concerning the production of these molecules and cells, and the necessary steps to ensure a strong intellectual property protection of these new molecules and approaches. These two days of exchanges allowed a rich discussion among the various actors in the field of therapeutic antibodies.

A systematic review, umbrella review, and quality assessment on clinical translation of stem cell therapy for knee osteoarthritis: Are we there yet?

BACKGROUND: The success of stem cell therapy for knee osteoarthritis (KOA) in preclinical animal models has accelerated the pace of clinical translation. However, it remains uncertain whether the current scientific evidence supports the clinical application of stem cells in treating KOA. A comprehensive evaluation of the safety and efficacy of stem cell therapies and scientific evidence quality is necessary. METHODS: Using "stem cells" and "knee osteoarthritis" as the search terms, several databases, including PubMed, Web of Science, Cochrane, Embase, and Clinicaltrials.gov, were searched on August 25, 2022, and updated on February 27, 2023. Clinical studies that reported adverse reactions (ARs) of stem cell therapy in KOA patients were included without limiting the type of studies. Quantitative systematic reviews of stem cell therapy for KOA that conducted meta-analysis were included. Two researchers conducted literature screening and data extraction independently, and the evidence quality was evaluated according to the Institute of Health Economics and AMSTAR 2 criteria. RESULTS: Fifty clinical studies and 13 systematic reviews/meta-analyses (SRs/MAs) were included. Nineteen ARs were reported in 50 studies, including five knee-related ARs, seven common ARs, and seven other ARs. Some studies reported over 10% prevalence of knee pain (24.5%; 95% CI [14.7%, 35.7%]), knee effusion (12.5%; 95% CI [4.8%, 22.5%]), and knee swelling (11.9%; 95% CI [3.5%, 23.5%]). Additionally, two studies have reported cases of prostate cancer and breast tumors, respectively. However, these two studies suggest that stem cell therapy does not bring significant ARs to patients. SRs/MAs results revealed that stem cell therapy relieved pain in patients over time but did not improve knee function. However, current clinical studies have limited evidence regarding study objectives, test designs, and patient populations. Similarly, SRs/MAs have inadequate evidence regarding study design, risk of bias assessment, outcome description, comprehensive discussion, and potential conflicts of interest. CONCLUSIONS: The inefficacy of stem cells, the risk of potential complications, and the limited quality of evidence from current studies precluded any recommendation for using stem cell products in patients with KOA. Clinical translation of stem cell therapies remains baseless and should be cautiously approached until more robust evidence is available. PROSPERO registration number: CRD42022355875.

A transcriptomics approach to expand therapeutic options and optimize clinical trials in oncology.

Background: The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies. Objective: Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies. Methods: Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate in silico the potential clinical benefit of specific treatments in a variety of metastatic solid tumors. Results: As example, high mRNA expression in tumor tissue compared to analogous normal tissue of c-MET and its ligand HGF correlated in silico with shorter overall survival (OS; p < 0.0001) and may constitute an independent prognostic marker for outcome of patients with metastatic solid tumors, suggesting a strategy to identify patients most likely to benefit from MET-targeted treatments. The prognostic value of gene expression of several immune therapy targets (PD-L1, CTLA4, TIM3, TIGIT, LAG3, TLR4) was investigated in non-small-cell lung cancers and colorectal cancers (CRCs) and may be useful to optimize the development of their inhibitors, and opening new avenues such as use of anti-TLR4 in treatment of patients with metastatic CRC. Conclusion: This in silico approach is expected to dramatically decrease the attrition of patient enrollment and to simultaneously increase the speed and detection of early signs of efficacy. The model may significantly contribute to lower toxicities. Altogether, our model aims to overcome the limits of current approaches.

Exploring the Role of Hypoxia-Inducible Carbonic Anhydrase IX (CAIX) in Circulating Tumor Cells (CTCs) of Breast Cancer.

Circulating tumor cells (CTCs) in the peripheral blood are believed to be the source of metastasis and can be used as a liquid biopsy to monitor cancer progression and therapeutic response. However, it has been challenging to accurately detect CTCs because of their low frequency and the heterogeneity of the population. In this study, we have developed an in vitro model of CTCs by using non-adherent suspension culture. We used this model to study a group of breast cancer cell lines with distinct molecular subtypes (TNBC, HER2+, and ER+/PR+). We found that, when these breast cancer cell lines lost their attachment to the extracellular matrix, they accumulated a subtype of cancer stem cells (CSC) that expressed the surface markers of stem cells (e.g., CD44+CD24-). These stem-like CTCs also showed high expressions of hypoxia-inducible gene products, particularly the hypoxia-inducible carbonic anhydrase IX (CAIX). Inhibition of CAIX activity was found to reduce CAIX expression and stem cell phenotypes in the targeted CTCs. Further studies are needed, using CTC samples from breast cancer patients, to determine the role of CAIX in CTC survival, CSC transition, and metastasis. CAIX may be a useful surface marker for the detection of CSCs in the blood, and a potential target for treating metastatic breast cancers.

Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials.

BACKGROUND: How much scientific evidence is there to show that stem cell therapy is sufficient in preclinical and clinical studies of spinal cord injury before it is translated into clinical practice? This is a complicated problem. A single, small-sample clinical trial is difficult to answer, and accurate insights into this question can only be given by systematically evaluating all the existing evidence. METHODS: The PubMed, Ovid-Embase, Web of Science, and Cochrane databases were searched from inception to February 10, 2022. Two independent reviewers performed the literature search, identified and screened the studies, and performed a quality assessment and data extraction. RESULTS: In total, 62 studies involving 2439 patients were included in the analysis. Of these, 42 were single-arm studies, and 20 were controlled studies. The meta-analysis showed that stem cells improved the ASIA impairment scale score by at least one grade in 48.9% [40.8%, 56.9%] of patients with spinal cord injury. Moreover, the rate of improvement in urinary and gastrointestinal system function was 42.1% [27.6%, 57.2%] and 52.0% [23.6%, 79.8%], respectively. However, 28 types of adverse effects were observed to occur due to stem cells and transplantation procedures. Of these, neuropathic pain, abnormal feeling, muscle spasms, vomiting, and urinary tract infection were the most common, with an incidence of > 20%. While no serious adverse effects such as tumorigenesis were reported, this could be due to the insufficient follow-up period. CONCLUSIONS: Overall, the results demonstrated that although the efficacy of stem cell therapy is encouraging, the subsequent adverse effects remain concerning. In addition, the clinical trials had problems such as small sample sizes, poor design, and lack of prospective registration, control, and blinding. Therefore, the current evidence is not sufficiently strong to support the clinical translation of stem cell therapy for spinal cord injury, and several problems remain. Additional well-designed animal experiments and high-quality clinical studies are warranted to address these issues.

Subacute traumatic spinal cord injury: a systematic review and network meta-analysis of therapeutic strategies based on bone marrow mesenchymal stromal cells in animal models.

BACKGROUND AIMS: To explore the optimal transplantation strategy of bone marrow mesenchymal stem cells in subacute traumatic spinal cord injury in animal experiments in order to provide reference for future animal studies and clinical research. METHODS: The PubMed, Embase and Web of Science databases were systematically searched (inception to January 4, 2022). Literature search, data extraction and bias assessment were performed by two independent reviewers. RESULTS: A total of 50 articles were included for analysis. Results of both traditional meta-analysis and network meta-analysis showed that high-dose (≥1 × 106) transplantation was significantly better than low-dose (<1 × 106) transplantation and intralesional transplantation was significantly better than intravenous transplantation. CONCLUSIONS: Given the limited quality of evidence from current animal studies, more high-quality head-to-head comparisons are needed in the future to delve into the optimal transplantation strategy for stem cells.

Loss of sphingosine kinase 2 promotes the expansion of hematopoietic stem cells by improving their metabolic fitness.

Hematopoietic stem cells (HSCs) have reduced capacities to properly maintain and replenish the hematopoietic system during myelosuppressive injury or aging. Expanding and rejuvenating HSCs for therapeutic purposes has been a long-sought goal with limited progress. Here, we show that the enzyme Sphk2 (sphingosine kinase 2), which generates the lipid metabolite sphingosine-1-phosphate, is highly expressed in HSCs. The deletion of Sphk2 markedly promotes self-renewal and increases the regenerative potential of HSCs. More importantly, Sphk2 deletion globally preserves the young HSC gene expression pattern, improves the function, and sustains the multilineage potential of HSCs during aging. Mechanistically, Sphk2 interacts with prolyl hydroxylase 2 and the Von Hippel-Lindau protein to facilitate HIF1α ubiquitination in the nucleus independent of the Sphk2 catalytic activity. Deletion of Sphk2 increases hypoxic responses by stabilizing the HIF1α protein to upregulate PDK3, a glycolysis checkpoint protein for HSC quiescence, which subsequently enhances the function of HSCs by improving their metabolic fitness; specifically, it enhances anaerobic glycolysis but suppresses mitochondrial oxidative phosphorylation and generation of reactive oxygen species. Overall, targeting Sphk2 to enhance the metabolic fitness of HSCs is a promising strategy to expand and rejuvenate functional HSCs.

Spinal Cord Injury: A Systematic Review and Network Meta-Analysis of Therapeutic Strategies Based on 15 Types of Stem Cells in Animal Models.

Objective: The optimal therapeutic strategies of stem cells for spinal cord injury (SCI) are fully explored in animal studies to promote the translation of preclinical findings to clinical practice, also to provide guidance for future animal experiments and clinical studies. Methods: PubMed, Web of Science, Embase, CNKI, Wangfang, VIP, and CBM were searched from inception to September 2021. Screening of search results, data extraction, and references quality evaluation were undertaken independently by two reviewers. Results and Discussion: A total of 188 studies were included for data analysis. Results of traditional meta-analysis showed that all 15 diverse types of stem cells could significantly improve locomotor function of animals with SCI, and results of further network meta-analysis showed that adipose-derived mesenchymal stem cells had the greatest therapeutic potential for SCI. Moreover, a higher dose (≥1 × 106) of stem cell transplantation had better therapeutic effect, transplantation in the subacute phase (3-14 days, excluding 3 days) was the optimal timing, and intralesional transplantation was the optimal route. However, the evidence of current animal studies is of limited quality, and more high-quality research is needed to further explore the optimal therapeutic strategies of stem cells, while the design and implementation of experiments, as well as measurement and reporting of results for animal studies, need to be further improved and standardized to reduce the risk when the results of animal studies are translated to the clinic. Systematic Review Registration: [website], identifier [registration number].

What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies.

Objective: The optimal transplantation timing of neural stem cells in spinal cord injury is fully explored in animal studies to reduce the risk of transformation to clinical practice and to provide valuable reference for future animal studies and clinical research. Method: Seven electronic databases, namely, PubMed, Web of Science, Embase, Wanfang, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched. The studies were retrieved from inception to November 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. Results and Discussion: Thirty-nine studies were incorporated into the final analyses. Based on the subgroup of animal models and transplantation dose, the results of network meta-analysis showed that the effect of transplantation in the subacute phase might be the best. However, the results of traditional meta-analysis were inconsistent. In the moderate-dose group of moderate spinal cord injury model and the low-dose group of severe spinal cord injury model, transplantation in the subacute phase did not significantly improve motor function. Given the lack of evidence for direct comparison between different transplantation phases, the indirectness of our network meta-analysis, and the low quality of evidence in current animal studies, our confidence in recommending cell transplantation in the subacute phase is limited. In the future, more high-quality, direct comparative studies are needed to explore this issue in depth.

Effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in a rat bladder tumor model.

Background: Investigate the effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in rat bladder tumor models. Methods: The bladder tumor model of 75 specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats aged 5-6 weeks was established by n-methyl-N-nitrosourea (MNU) bladder perfusion induction, and the model rats were randomly divided into model group, low-dose (L-dose) group, medium-dose (M-dose) group, high-dose (H-dose) group, and positive drug (hydroxycamptothecine, HCPT) group. L-dose group, M-dose group, and H-dose group were treated with 5 g/kg, 10 g/kg, and 20 g/kg, respectively. The HCPT group was treated with 2 mg/kg hydroxycamptothecin at 1 mL/kg once a week and the model group were treated with the same amount of normal saline for 4 weeks. The quality of bladder cancer tissues in each group was measured. The pathological changes and microvascular density of bladder tissues were observed, and the apoptosis rate of vascular endothelial growth factor (VEGF), tumor tissue and the protein expression levels of factor associated suicide (Fas), factor associated suicide ligand (FasL) and Caspase3 in bladder tissues were detected. Results: Bladder cancer was induced 14 weeks after initial bladder perfusion with MNU. In the model group, epithelial cells of bladder tissue showed atypically hyperplasia with various sizes and disorders. After treatment with Stellera chamaejasme, the hematoxylin-eosin (HE) scores, bladder weight, microvascular density, and VEGF were significantly decreased, and the tumor inhibition rate, cell apoptosis, and the expression of apoptosis-related proteins Fas, FasL, and Caspase3 were significantly increased in the bladder tissue. The above changes were dose-dependent with Stellera chamaejasme. Conclusions: MNU can be used to prepare a rat bladder cancer model. Stellera chamaejasme has a good therapeutic effect on rat bladder cancer, which may inhibit the progression of bladder cancer by inhibiting micro-angiogenesis and inducing the apoptosis of bladder tumor cells.

Melanin nanoparticles enhance the neuroprotection of mesenchymal stem cells against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense.

Polydopamine nanoparticles are artificial melanin nanoparticles (MNPs) that show strong antioxidant activity. The effects of MNPs on the neuroprotection of mesenchymal stem cells (MSCs) against hypoxic-ischemic injury and the underlying mechanism have not yet been revealed. In this study, an oxygen-glucose deprivation (OGD)-injured neuron model was used to mimic neuronal hypoxic-ischemic injury in vitro. MSCs pretreated with MNPs and then cocultured with OGD-injured neurons were used to investigate the potential effects of MNPs on the neuroprotection of MSCs and to elucidate the underlying mechanism. After coculturing with MNPs-pretreated MSCs, MSCs, and MNPs in a transwell coculture system, the OGD-injured neurons were rescued by 91.24%, 79.32%, and 59.97%, respectively. Further data demonstrated that MNPs enhanced the neuroprotection against hypoxic-ischemic injury of MSCs by scavenging reactive oxygen species and superoxide and attenuating neuronal apoptosis by deactivating caspase-3, downregulating the expression of proapoptotic Bax proteins, and upregulating the expression of antiapoptotic Bcl-2 proteins. These findings suggest that MNPs enhance the neuroprotective effect of MSCs against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense, which could provide some evidence for the potential application of combined MNPs and MSCs in the therapy for ischemic stroke.