Can self-powered piezoelectric materials be used to treat disc degeneration by means of electrical stimulation?

Intervertebral disc degeneration (IDD) due to multiple causes is one of the major causes of low back pain (LBP). A variety of traditional treatments and biologic therapies are currently used to delay or even reverse IDD; however, these treatments still have some limitations. Finding safer and more effective treatments is urgent for LBP patients. With increasing reports it has been found that the intervertebral disc (IVD) can convert pressure loads from the spine into electrical stimulation in a variety of ways, and that this electrical stimulation is of great importance in modulating cell behavior, the immune microenvironment and promoting tissue repair. However, when intervertebral disc degeneration occurs, the normal structures within the IVD are destroyed. This eventually leads to a weakening or loss of self-powered. Currently various piezoelectric materials with unique crystal structures can mimic the piezoelectric effect of normal tissues. Based on this, tissue-engineered scaffolds prepared using piezoelectric materials have been widely used for regenerative repair of various types of tissues, however, there are no reports of their use for the treatment of IDD. For this reason, we propose to utilize tissue-engineered scaffolds prepared from piezoelectric biomaterials with excellent biocompatibility and self-powered properties to be implanted into degenerated IVD to help restore cell type and number, restore extracellular matrix, and modulate immune responses. It provides a feasible and novel therapeutic approach for the clinical treatment of IDD.

Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy.

BACKGROUND: Stem cell-based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small-scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. METHODS: We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. RESULTS: We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT-related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. CONCLUSIONS: Standardization plays an important role in the sustained, rapid and healthy development of SCT.

How much carbon storage will loss in a desertification area? Multiple policy scenario analysis from Gansu Province.

Carbon storage plays a pivotal role in addressing climate change, maintaining ecological equilibrium, and fostering sustainable development. Gansu Province, situated in the arid to semi-arid region of Northwestern China, is confronted with substantial carbon storage losses as a result of ongoing ecological land desertification processes. However, studies on carbon storage loss under various scenarios in desertified regions are seldom reported. In this study, we delineated the ecological red line using quantified indicators encompassing multiple ecosystem service functions and ecological vulnerability sensitivity. Furthermore, we projected future land use and carbon storage transformations under multiple policy scenarios employing the patch-generating land use simulation (PLUS) model. Lastly, we unveiled spatial disparities in the driving factors behind alterations in carbon storage by geographically weighted regression model. Our findings suggest that: (1) The delineated ecological red line covers an area of 11.8 × 104 km2, approximately 27 % of the total land area of Gansu Province. (2) Quantitative findings reveal that the overall accuracy of the PLUS model reached an impressive 0.975, accompanied by a Kappa coefficient of 0.964, thus affirming the model's exceptional applicability. (3) Under the base line scenario, Gansu Province's carbon storage witnesses a consistent decline from 2000 to 2050, with a substantial total loss of 1.62 × 107 t over the ensuing three decades. The ecological red line scenario, by controlling 27 % of the land area in Gansu Province, achieves a 61.7 % effect of the global ecological scenario by 2050, thus reversing the declining trend in carbon storage. (4) Natural factors primarily influence carbon storage in the southeastern region, while human activity factors are distributed in the central region. This study offers scientifically robust policy recommendations to facilitate the attainment of carbon neutrality objective.

Electrospun fibers integrating enzyme-functionalized metal-organic frameworks for postoperative tumor recurrence inhibition and simultaneously wound tissue healing.

The tumor recurrence and infected wound tissue defect are the major clinical challenges after the surgical treatment of primary chest wall cancer. Herein, to address the above issues, blending electrospinning was applied to incorporate glucose oxidase (GOx) loaded Zn/Cu-based bimetallic zeolitic imidazolate frameworks (GOx/BMOFs) into polyurethane (PU) fibers, which were designed for effective cancer therapy with improved wound healing. The release of Cu2+ and GOx could accomplish the conversion from Cu2+ to Cu+ through the glutathione (GSH) depletion and provide additional H2O2 from glucose by GOx catalysis, respectively, which further underwent the Fenton-like reaction to produce toxic hydroxyl radical (OH). The tumor cells (human fibrosarcoma cells) could be effectively killed in vitro and in vivo through the synergistic chemodynamic therapy and starvation therapy. Moreover, the electrospun fiber platform could support the adhesion and proliferation of wound tissue cells, and also show the antibacterial ability owing to the functional agents in the fibers, thereby accelerating the infected wound repair in vivo. This work may offer a reliable and effective fiber biomaterial for localized chest wall tumor therapy and simultaneous tissue regeneration.

GABAergic neurons maturation is regulated by a delicate network.

Gamma-aminobutyric acid-expressing (GABAergic) neurons are implicated in a variety of neuropsychiatric disorders, such as epilepsy, anxiety, autism, and other pathological processes, including cerebral ischemia injury and drug addiction. Therefore, GABAergic neuronal processes warrant further research. The development of GABAergic neurons is a tightly controlled process involving the activity of multiple transcription and growth factors. Here, we focus on the gene expression pathways and the molecular modulatory networks that are engaged during the development of GABAergic neurons with the goal of exploring regulatory mechanisms that influence GABAergic neuron fate (i.e., maturation). Overall, we hope to provide a basis for clarifying the pathogenesis of neurodegenerative disorders.

Successful surgical treatment of Cronkhite-Canada Syndrome with bilateral flail chest: a case report.

BACKGROUND: Development of multiple rib fractures leading to bilateral flail chest in Cronkhite-Canada Syndrome (CCS) has not been reported. CASE PRESENTATION: A 59-year-old man presented with complaints of fatigue, chest pain, respiratory distress and orthopnea requiring ventilatory support to maintain oxygenation. CCS with bilateral anterior and posterior flail chest due to multiple rib fractures (2nd-10th on the right side and 2nd-11th on the left side). He underwent open reduction and anterior and posterior internal fixation using a titanium alloy fixator and a nickel-titanium memory alloy embracing fixator for chest wall reconstruction. He recovered gradually from the ventilator and showed improvement in his symptoms. He gained about 20 kg of weight in the follow up period (6 months after discharge from the hospital). CONCLUSION: CCS is a rare, complex disease that increases the risk of developing multiple rib fractures, which can be successfully treated with open reduction and internal fixation.

Long Non-coding RNA MEG3 Attenuates the Angiotensin II-Induced Injury of Human Umbilical Vein Endothelial Cells by Interacting With p53.

Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of cardiovascular disease. This study aimed to investigate the role of maternally expressed gene 3 (Meg3) in endothelial cell injury. A lncRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVECs). Cell viability, apoptosis, and migration were then assessed Ang II-treated HUVECs. qRT-PCR and western blotting were performed to detect the expression level of p53 after Meg3 knockdown and overexpression. We observed that Ang II treatment decreased the Meg3 level in HUVECs. Next, both knockdown of Meg3 and Ang II decreased cell viability, increased apoptotic cell rate and impair migration function in HUVECs. Furthermore, overexpression of Meg3 inhibited cell apoptosis, and increased cell migration by enhancing p53 transcription on its target genes, including CRP, ICAM-1, VEGF, and HIF-1α. Our findings indicate that Meg3 might be associated with cardiovascular disease development.

Recurrence of multiple metastases after surgical removal of a primary malignant solitary fibrous tumor from the main bronchus: A case report.

RATIONALE: Limited knowledge is available regarding solitary fibrous tumors (SFTs), about 15% of which are malignant. In particular, the long-term survival of patients with malignant SFTs (mSFTs), the disease course, and the potential for recurrence of second primary tumors or distant metastases are largely undetermined. PATIENT CONCERNS: We report a rare case in which an mSFT was found at the main bronchus of the right lung of a 37-year-old man. DIAGNOSIS: The tumor cells of mSFT were spindle-shaped and expressed antigen Ki-67, B-cell lymphoma 2, cluster of differentiation 31, and vimentin. INTERVENTIONS: A total pneumonectomy was performed. OUTCOMES: The patient developed fibrosarcoma of the small intestine at 6 months, as well as extensive pleural and peritoneal metastases at 1 year, after removal of the primary mSFT from the right main bronchus. LESSONS: From these findings, we expect that patients with primary mSFT, especially of the lung, have a high potential to develop second tumors or distant metastases. Close monitoring after surgery is necessary to improve the outcomes of these patients.

Cytotoxicity, organ distribution and morphological effects of melamine and cyanuric acid in rats.

Melamine (Mel) is used widely as a basic organic chemical intermediate in several products. Within the last 10 years there have been two high-profile Mel exposures that caused toxicological concern, especially regarding food adulteration. OBJECTIVE: This study aimed to determine the toxicity of Mel and one of its homologs, cyanuric acid (Cya), in vitro and in vivo. MATERIALS AND METHODS: The IC50 of Mel and Cya was determined by the MTT assay in NRK-52E and 293T cell lines. Organ-specific toxicity was assessed using the following dosing paradigm of Wistar rats: group 1: normal saline; group 2: Mel (180 mg/kg); group 3: Cya (150 mg/kg); and group 4: Mel (180 mg/kg) + Cya (150 mg/kg). RESULTS: The NRK cell toxicity studies on Mel and Cya revealed IC50 values of 1.89 mg/mL and 4.20 mg/mL, respectively. Similarly, Mel and Cya IC50 values in 293T cells were 2.07 mg/mL and 3.71 mg/mL, respectively. Histopathologic studies revealed crystals in the renal medulla-cortex and loss of chief cells in the lining of the stomach in the group receiving Mel plus Cya. HPLC-MS analysis of organ homogenates showed that the concentration of Mel was greatest in the animals receiving a combination of both Mel and Cya. DISCUSSION AND CONCLUSION: Mel is more toxic than its homolog Cya. The kidney is the most affected organ. Mel was present at high concentration not only in the kidneys, but also in the uterus and liver, informing the scope of future studies on the mechanism of Mel and Cya toxicity.

Combined treatment of XIAP-targeting shRNA and celecoxib synergistically inhibits the tumor growth of non­small cell lung cancer cells in vitro and in vivo.

X-linked inhibitor of apoptosis protein (XIAP) has been shown to be highly expressed in lung cancer, but not in normal lung tissue, which makes it an attractive target for lung cancer treatment. Celecoxib (CXB), a cyclooxygenase-2 inhibitor, is in wide clinical use for the treatment and prevention of non-small cell lung cancer (NSCLC). Therefore, in our study, we combined short hairpin RNA (shRNA) targeted to XIAP (XIAP-shRNA) with CXB and tested the effects of this combination on lung cancer cells to identify more effective therapeutics against lung cancer. An XIAP-shRNA plasmid was constructed and transfected into the A549 NSCLC cell line. The cells were then treated with CXB and XIAP-shRNA alone or in combination for indicated time periods, and the treatments were assessed for their effects on cell proliferation, apoptosis, migration, invasion and receptor signaling using the MTT, TUNEL, wound healing and Matrigel invasion assays and western blotting, respectively. In addition, an NSCLC xenograft model was prepared to observe tumor growth. It was found that both CXB and XIAP­shRNA significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in vitro, as well as suppressed tumor growth in vivo. Moreover, the combination of the agents significantly enhanced these effects compared to the single agent treatments. We also found that the combination treatment significantly suppressed constitutive phosphorylation of PI3K and AKT, which may contribute to the inhibition of tumor growth. These findings suggest that the combination of XIAP­shRNA and CXB is a promising drug candidate for the treatment of NSCLC.

Combining sorafenib with celecoxib synergistically inhibits tumor growth of non-small cell lung cancer cells in vitro and in vivo.

Although inhibition of cyclooxygenase-2 (COX-2) or the vascular endothelial growth factor receptor (VEGFR) has been shown to be a promising antitumor strategy in non-small cell lung cancer (NSCLC), the therapeutic efficacy is limited due to inherent tumor resistance. In the present study, we selected sorafenib (SOR), a VEGFR inhibitor, in combination with celecoxib (CXB), a COX-2 inhibitor, for suppressing tumor growth and simultaneously for reducing doses of both drugs for the treatment of NSCLC. The effects of SOR combined with CXB were examined in A549 cells (an NSCLC cell line). Assays of proliferation, apoptosis, cell cycle distribution and receptor signaling were performed. We found that treatment with the combination of low concentrations of SOR and CXB significantly suppressed the proliferation of A549 tumor cells in vitro and suppressed tumor growth in vivo when compared to the actions of either agent alone. The results also showed that the combination of SOR and CXB significantly increased the induction of apoptosis and decreased the expression of inhibitor of apoptosis genes, survivin and Bcl-2 (p<0.01). Furthermore, the combination treatment significantly suppressed constitutive phosphorylation of MEK and ERK, which may contribute to the inhibition of tumor growth. Taken together, our findings revealed that this additive combination of SOR and CXB is a potential drug candidate for the treatment of NSCLC.

Inhibitory effect of celecoxib in lung carcinoma by regulation of cyclooxygenase-2/cytosolic phospholipase A2 and peroxisome proliferator-activated receptor gamma.

Celecoxib is a potent nonsteroid anti-inflammatory drug (NSAID) that has demonstrated great promise in cancer chemoprevention and treatment. The goal of this study was to determine the inhibitory effect and mechanism of celecoxib on Lewis lung carcinoma. The effect of celecoxib on viability of Lewis lung carcinoma cells was assessed with methyl thiazolyl tetrazolium (MTT) assay. Apoptosis and the mitochondrial membrane potential were detected by flow cytometric assay. The protein expression of cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor gamma (PPARγ) were determined by Western blot analysis. The concentrations of arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) in culture supernatants were measured by the methods of RP-HPLC and PGE(2)-specific ELISA, respectively. Celecoxib inhibited the proliferation of Lewis lung carcinoma and induced apoptosis in a dose-dependent manner by breakdown of mitochondrial membrane potential. The protein expressions of cPLA(2) and PPARγ were upregulated, but COX-2 protein expression was downregulated in the Lewis lung carcinoma cells exposed to celecoxib. The amount of AA was increased and PGE(2) was decreased in the culture supernatant, respectively. The ratio of AA to PGE(2) was increased in a dose-dependent manner. The major findings in this study are that celecoxib could inhibit the viability of Lewis lung carcinoma cells by interference of the AA pathway and upregulation of PPARγ simultaneously, which are novel and important since the molecular mechanisms of celecoxib underlying the anti-neoplastic effects remain unclear.