Synthesis of spiro[indolenine]-methanofullerenes via Deoxofluor promoted deoxygenative cyclopropanation of 1,2-(3-indole)-fullerenols.

Deoxofluor-promoted intramolecular cyclopropanation of 1,2-(3-indole)fullerenols has been developed as a straightforward and efficient protocol for the synthesis of various spiro[indolenine]-methanofullerenes. This approach exhibits low cost, operational simplicity, and convenient conditions, and thus has potential application value.

Three-Dimensional Bioprinting of Decellularized Extracellular Matrix-Based Bioinks for Tissue Engineering.

Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.

Effect of Aidi injection plus chemotherapy on gastric carcinoma: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To conduct a Meta-analysis of studies on the effect of Aidi injection combined with chemotherapy versus chemotherapy alone in the treatment of gastric cancer (GC). METHODS: Nine electronic databases and six gray literature databases were comprehensively searched until April 20, 2013. Two reviewers independently selected and assessed included trials according to the inclusion and exclusion criteria. The risk of bias tool from the Cochrane Handbook version 5.1.0 was used to assess trial quality. All calculations were performed using Review Manager 5.0. RESULTS: Thirty-two studies including 1927 participants met the inclusion criteria, most of which were low quality. Compared with chemotherapy alone, Aidi injection plus the same chemotherapy significantly improved the effective rate [OR = 1.52, 95% CI (1.24, 1.86), P < 0.0001], clinical beneficial rate [OR = 1.77, 95% CI (1.33, 2.36), P < 0.0001], and quality of life [OR = 3.02, 95% CI (2.39, 3.82), P < 0.000 01]. There was a significant improvement in nausea and vomiting incidence [OR = 0.34, 95% CI (0.24, 0.47), P < 0.000 01], diarrhea [OR = 0.47, 95% CI (0.33, 0.69), P < 0.000 01], leukopenia (III-IV) [OR = 0.34, 95% CI (0.23, 0.51), P = 0.05], hemoglobin decrease (III-IV) [OR = 0.42, 95% CI (0.18-1.00), P = 0.05], thrombocytopenia (III-IV) [OR = 0.46, 95% CI (0.22, 0.96), P = 0.04], and damage to liver function [OR = 0.36, 95% CI (0.24, 0.54), P < 0.00001]. CONCLUSION: Aidi injection combined with chemotherapy significantly improved the clinical effect of chemotherapy, reducing the incidence of adverse events. Use of the CONSORT statement for randomized controlled trials is recommended for stricter reporting.

Functional Hydrogel Co-Remolding Migration and Differentiation Microenvironment for Severe Spinal Cord Injury Repair.

Spinal cord injury (SCI) activates nestin+ neural stem cells (NSCs), which can be regarded as potential seed cells for neuronal regeneration. However, the lesion microenvironment seriously hinders the migration of the nestin+ cells to the lesion epicenter and their differentiation into neurons to rebuild neural circuits. In this study, a photosensitive hydrogel scaffold is prepared as drug delivery carrier. Genetically engineered SDF1α and NT3 are designed and the scaffold is binary modified to reshape the lesion microenvironment. The binary modified scaffold can effectively induce the migration and neuronal differentiation of nestin+ NSCs in vitro. When implanted into a rat complete SCI model, many of the SCI-activated nestin+ cells migrate into the lesion site and give rise to neurons in short-term. Meanwhile, long-term repair results also show that implantation of the binary modified scaffold can effectively promote the maturation, functionalization and synaptic network reconstruction of neurons in the lesion site. In addition, animals treated with binary scaffold also showed better improvement in motor functions. The therapeutic strategy based on remolding the migration and neuronal differentiation lesion microenvironment provides a new insight into SCI repair by targeting activated nestin+ cells, which exhibits excellent clinical transformation prospects.

Geometry and temperature dependence of meso-aryl rotation in strained metalloporphyrins: adjustable turnstile Molecules.

The rotation of meso-aryl groups in porphyrins depends on the degree of macrocyclic distortion and is also influenced by the surrounding temperature. Dynamic NMR methods and crystal structures of series of nonplanar metalloporphyrins reveal that macrocyclic distortion lowers the rotational barrier by weakening the nonbinding interactions of neighboring groups, while increased temperature allows the rotational barrier to be overcome more readily. Two empirical methods are developed to acquire the rotational barrier. This type of strained molecule can act as an adjustable molecular turnstile through adjusting the degree of macrocyclic distortion and changing the surrounding temperature.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys.

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Dual-Cues Laden Scaffold Facilitates Neurovascular Regeneration and Motor Functional Recovery After Complete Spinal Cord Injury.

Complete transection spinal cord injury (SCI) severely disrupts the integrity of both neural circuits and the microvasculature system. Hence, fabricating a functional bio-scaffold that could coordinate axonal regeneration and vascular reconstruction in the lesion area may emerge as a new paradigm for complete SCI repair. In this study, a photosensitive hydrogel scaffold loaded with collagen-binding stromal cell-derived factor-1a and Taxol liposomes is capable of inducing migration of endothelial cells and promoting neurite outgrowth of neurons in vitro. In addition, when implanted into a rat T8 complete transection SCI model, the above dual-cues laden scaffold exhibits a synergistic effect on facilitating axon and vessel regeneration in the lesion area within 10 days after injury. Moreover, long-term therapeutic effects are also observed after dual-cues laden scaffold implantation, including revascularization, descending and propriospinal axonal regeneration, fibrotic scar reduction, electrophysiological recovery, and motor function improvement. In summary, the dual-cues laden scaffold has good clinical application potential for patients with severe SCI.

Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair.

The limited regrowth of transected axons and insufficient regeneration of lost neurons in adult mammals collectively hinder complete spinal cord injury (SCI) repair. Hence, designing an ideal bio-scaffold which could coordinate the regeneration of axons and neurons in situ might be able to effectively facilitate the reconstruction of neural circuits and the recovery of nerve function after complete SCI. In this study, a sponge-like collagen scaffold with good drug release characteristics and good nerve cell compatibility was prepared and used as a drug delivery platform. When doubly modified with Taxol liposomes and collagen-binding neurotrophic factor 3, the scaffold dually alleviated myelin-derived inhibition on neurite outgrowth of neurons and neuronal differentiation of neural stem cells in vitro. Meanwhile, the binary-drug modified scaffold was also able to simultaneously promote both axonal and neuronal regeneration when implanted into a complete transected SCI model. Additionally, the regenerated axons and neurons throughout the lesion site formed extensive synaptic connections. Finally, complete SCI rats that received binary scaffold implantation exhibited optimal neuroelectrophysiological recovery and hindlimb locomotor improvement. Taken together, implantation of the binary scaffold can establish neural bridging networks for functional recovery, representing a clinically promising strategy for complete SCI repair.

A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing.

Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients. Some studies have shown that separate administration of vascular endothelial growth factor (VEGF) or stromal cell derived factor 1α (SDF-1α) exhibited a therapeutic effect in promoting angiogenesis in the wound healing process. In this study, a collagen membrane is prepared as a drug delivery scaffold to investigate whether combined administration of SDF-1α and VEGF has a synergistic therapeutic effect on diabetic wound healing. We specifically fused a collagen-binding domain (CBD) with SDF-1α and VEGF separately, and sustained release of the two recombinant proteins from the collagen scaffold is successfully observed. Meanwhile, when a CBD-VEGF and CBD-SDF-1α co-modified scaffold is implanted in a diabetic rat skin wound model, it not only shows a synergistic effect in facilitating angiogenesis but also reduces inflammation in the short-term. Moreover, long-term results reveal that the co-modified scaffold is also able to enhance rapid wound healing, promote blood vessel regeneration, and assist cell proliferation, re-epithelialization and extracellular matrix accumulation. Taken together, our study indicates that the CBD-VEGF and CBD-SDF-1α co-modified scaffold helps in quick recovery from diabetic wounds by coordinating angiogenesis and inflammation.

The role of kynurenine pathway and kynurenic aminotransferase alleles in postpartum depression following cesarean section in Chinese women.

OBJECTIVES: A growing body of data indicates that the kynurenine pathway may play a role in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenic aminotransferase (KAT) is an important kynurenine pathway enzyme, catalyzing kynurenine (KYN) into kynurenic acid (KYNA). This study investigated as to whether genetic variations in KAT are associated with PDS. METHODS: A cohort of 360 Chinese women scheduled to undergo cesarean delivery was enrolled into this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13. A total of eight KAT single nucleotide polymorphisms (SNPs) were genotyped and their association with PDS investigated. Serum concentrations of KYN, KYNA, and quinolinic acid (QUIN) in women with or without PDS were also measured. This allowed the determination of the KYNA/KYN ratio, which is reflective of KAT activity. RESULTS: Postpartum depressive symptoms incidence was 7.2%. Advanced maternal age, lower education, antenatal depression, and postpartum blues were risk factors for PDS (p < .05). Women with PDS, versus non-PDS, had heightened KYN levels one day prior to surgery (ante-d1) (p < .05), as well as having significantly lower KYNA and higher QUIN levels at postnatal day three (post-d3) (p < .05). Women with, versus without, PDS also had a significantly higher QUIN/KYNA ratio at post-d3 (p < .05). KAT activity was significantly lower in women with, versus without, PDS at ante-d3 (p < .05). No significant association was evident between the KAT SNPs and PDS. CONCLUSION: Our data support a role for alterations in the kynurenine pathway in the pathogenesis of PDS, although no significant association was found for the eight tested KAT SNPs with PDS.

Insulin Resistance Predicts Postoperative Cognitive Dysfunction in Elderly Gastrointestinal Patients.

BACKGROUND: Members of the aging population who undergo surgery are at risk of postoperative cognitive dysfunction (POCD). Exploring an effective and reliable early predictor of POCD is essential to the identification of high-risk patients and to making prospective decisions. The purpose of this study was to examine whether preoperative insulin resistance is an independent predictor of POCD. METHODS: A total of 124 patients aged 60 years and older and who were scheduled for gastrointestinal surgery were enrolled in a prospective observational clinical study. All participants completed a battery of neuropsychological tests before surgery and 7 days later. POCD was defined as a decline of at least 1.5 SD on two or more of neuropsychological tests. Plasma concentration of the tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and S-100ß protein were measured. The status of insulin resistance was assessed by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The relationship between HOMA-IR and POCD was assessed by Multivariable logistic regression models and the receiver operating characteristic (ROC) curve. RESULTS: Fifty one patients (41.1%) were diagnosed with POCD at 7 days after surgery. Preoperative HOMA-IR values of the POCD group were significantly higher than the non-POCD group. Furthermore, CRP and TNF-α levels of the POCD group were significantly higher at each postoperative time point (P < 0.05). The preoperative HOMA-IR value was an independent predictor of POCD (adjusted OR 1.88, 95% CI, 1.18-2.99) even after adjust for confounding variables, and when dichotomized, individuals above the HOMA-IR threshold (HOMA-IR > 2.6) had a three-times higher risk of POCD (OR 3.26; 95% CI, 1.07-9.91) compared to individuals below the threshold. The areas under the ROC curve of HOMA-IR was 0.804 (95% CI, 0.725-0.883; P < 0.001). The optimal cut-off value was found to be 0.583, with a sensitivity of 84.3% and specificity of 74%. The HOMA-IR value was positively associated with the TNF-α concentration at baseline (R 2 = 0.43, P < 0.01) and 1 day after surgery (R 2 = 0.3861, P < 0.01). CONCLUSION: Preoperative insulin resistance is an effective predictor for the occurrence of POCD. Targeted prevention and treatment strategies of insulin resistance may be effective interventions of patients at risk for POCD.

MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast cancer by targeting the RAB5A.

MiR-130a has been demonstrated to play important roles in many types of cancers. Nevertheless, its biological function in breast cancer remains largely unknown. In this study, we found that the expression level of miR-130a was down-regulated in breast cancer tissues and cells. Overexpression of miR-130a was able to inhibit cell proliferation, invasion and migration in MCF7 and MDA-MB-435 cells. With the bioinformatics analysis, we further identified that RAB5A was a directly target of miR-130a, and its mRNA and protein level was negatively regulated by miR-130a. Immunohistochemistry verified RAB5A was upregulated in breast cancer tissues. Therefore, the data reported here demonstrate that miR-130a is an important tumor suppressor in breast cancer, and imply that miR-130a/RAB5A axis have potential as therapeutic targets for breast cancer.

The effect of exogenous creatine phosphate on myocardial injury after percutaneous coronary intervention.

OBJECTIVE: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). METHOD: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3. RESULTS: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively). CONCLUSION: Exogenous CP was helpful to reduce myocardial injury after PCI.

Conversion of electron configuration of iron ion through core contraction of porphyrin: implications for heme distortion.

It was demonstrated experimentally that nonplanar iron porphyrins can be induced to undergo a conversion in their electronic configuration to form a cross-hybrid transition by compressing the macrocyclic core size for the central metal ion. A series of monostrapped iron porphyrins were used as model systems, and their electronic properties were probed using electron spin resonance and differential spectral analyses. These results indicate that the formation of a cross-hybrid transition stage is related to the stability of the high-valence state and potent oxidizing ability of the central iron ion.