Chemical components and against alzheimer's disease effects of the calyxes of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Physalis alkekengi L. var. franchetii (Mast.) Makino (PA), a traditional Chinese medicine, is utilised for treating dermatitis, sore throat, dysuria, and cough. This research aimed to identify the main constituents in the four extracted portions from the calyces of PA (PAC) utilising ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The Alzheimer's disease (AD) mice model was induced by D-galactose (D-gal) combined with aluminium chloride (AlCl3). Subsequent investigation into the underlying mechanisms involved behavioural and histopathological observations. The results demonstrated that four extracted portions of PAC (PACE) significantly enhanced memory and learning abilities in the Morris water maze. The concentrations of Aß, tau and p-tau in brain tissue exhibited a significant decrease relative to the model group. Moreover, the four PACE treatment groups increased the glutathione (GSH) and superoxide dismutase (SOD) levels, while concurrently reducing malondialdehyde (MDA), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels. In summary, the current study demonstrates that the four PACE formulations exhibit beneficial anti-AD properties, with the most pronounced efficacy observed in the EA group. Additionally, PAC shows potential in mitigating neuroinflammation and oxidative damage by inhibiting the TLR4/NF-κB signalling pathway. This research lays a theoretical groundwork for the future clinical development and utilisation of PAC in treating AD.

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma.

BACKGROUND: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined. METHODS: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments. RESULTS: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination. CONCLUSION: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges.

Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable "biological gas" (CO, H2 , H2 S, NO, O2 , O3 , and N2 O) or "noble gas" (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO-CO, HIF-1α/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF-1α/ERK activation. Primary findings also reveal that the need to utilize cutting-edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad-spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma.

The intrapleural administration with thymic peptides in malignant pleural effusion: A clusteredsystematicreview and meta-analysis.

BACKGROUND: Thymic peptides (TPs) are often used to control malignant pleural effusion (MPE). So, we performed a clustered systematic review and meta-analysis to clarify the treatment regimens of TPs for MPE, demonstrate their clinical effectiveness and safety, and reveal the indications and optimal usage for a desired effectiveness. MATERIALS AND METHODS: We collected all trials of TPs for MPE from Chinese and English databases (from inception until May 2021). After evaluating their bias risk, we pooled the data from each regimen using the meta-analysis or descriptive analysis, and summarized the evidence quality using the Grading of Recommendation Assessment, Development and Evaluation approach (GRADE). RESULTS: Thirty-four trials were clustered into TPs for MPE from lung cancer or miscellaneous tumors. The TPs combined with chemical agents were mainly used in MPE from lung cancer. All five regimens, only thymosin with oxaliplatin (L-OHP) significantly improved the complete response (CR) [2.40 (1.84 to 3.13)], quality of life [2.04 (1.20 to 3.48)], 0.5- and 1-year overall survival (OS) rate [5.75 (3.02 to 10.92) and 5.29, (1.71 to 16.36)]. It also up-regulated the T lymphocyte levels, and reduced the pleurodesis failure, disease progression and adverse events. In patients with moderate to large volume, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥ 3 months, the thymosin (300 mg/time, one time/week and lasting two to eight times) with oxaliplatin (100 mg/m2) achieved a desired response. Most results were moderate quality. CONCLUSIONS: The current evidences indicate that the TPs are important pleurodesis agents, which combination with chemical agents are mainly used in MPE from lung cancer. The thymosin with L-OHP is a main regimen, which shows a significant improvement in clinical responses, antitumor immunity, and with a reasonable security. The evidence also provides indications and optimal usage for achieving a desired effectiveness.

Identification and Validation of an Immune and Ferroptosis-Combined Index for Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) is among the major health problems around the world. Reliable biomarkers for NSCLC are still needed in clinical practice. We aimed to develop a novel ferroptosis- and immune-based index for NSCLC. Methods: The training and testing datasets were obtained from TCGA and GEO databases, respectively. Immune- and ferroptosis-related genes were identified and used to establish a prognostic model. Then, the prognostic and therapeutic potential of the established index was evaluated. Results: Intimate interaction of immune genes with ferroptosis genes was observed. A total of 32 prognosis-related signatures were selected to develop a predictive model for NSCLC using LASSO Cox regression. Patients were classified into the high- and low-risk group based on the risk score. Patients in the low-risk group have better OS in contrast with that in the high-risk group in independent verification datasets. Besides, patients with a high risk score have shorter OS in all subgroups (T, N, and M0 subgroups) and pathological stages (stage I, II, and III). The risk score was positively associated with Immune Score, Stromal Score, and Ferroptosis Score in TCGA and GEO cohorts. A differential immune cell infiltration between the high-risk and the low-risk groups was also observed. Finally, we explored the significance of our model in tumor-related pathways, and different enrichment levels in the therapeutic pathway were observed between the high- and low-risk groups. Conclusion: The present study developed an immune and ferroptosis-combined index for the prognosis of NSCLC.

IncRNA LUCAT1 acts as a Potential Biomarker and Demonstrates Malignant Biological Behaviors in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains the fourth-leading malignancy worldwide and has a high mortality rate. Accumulating evidence reveals that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and metastasis and can be used as potential biomarkers for diagnosis and prognosis. METHODS: We downloaded gene expression profiles from the National Center of Biotechnology Information Gene Expression Omnibus (GEO), screened lncRNAs differentially expressed in gastric cancer tissues and adjacent tissues, and then constructed a lncRNA-miRNA-mRNA network. Seventy patients with gastric cancer were divided into two groups according to different clinical characteristics. The expression of lncRNA LUCAT1 in gastric cancer was detected by reverse transcription polymerase chain reaction (RT-PCR). The AGS and SGC-7901 cell lines were used in CCK8 assay, apoptosis, cell cycle test, transwell assay, and wound healing assay. RESULTS: The expression level of LUCAT1 was associated with tumor diameter (p < 0.001), tissue differentiation grade (p = 0.026), and LNM status (p = 0.020) in GC. The results showed that the lncRNA LUCAT1 could promote the proliferation, invasion, and migration of GC cells, inhibit the apoptosis of GC cells, and affect the process of cell cycles. CONCLUSIONS: The lncRNA LUCAT1 may be used as a potential biomarker for early signs of LNM in GC and may play a crucial role in the development of GC.

Outcomes and prognostic factors associated with 180-day mortality in Taiwanese pediatric patients with Hemophagocytic Lymphohistiocytosis.

BACKGROUND/PURPOSE: Hemophagocytic lymphohistiocytosis (HLH), a rarely occurring syndrome with various triggers, is associated with early mortality. Owing to a lack of sufficient corresponding data in Taiwan, this study aimed to identify the outcome and potential factors associated with 180-day mortality in pediatric HLH. METHODS: This retrospective study analyzed clinical and laboratory data on pediatric patients diagnosed with HLH at our institute (1995-2019). Logistic regression analysis was conducted to determine the associations between various factors and 180-day mortality. RESULTS: Overall, 48 patients had HLH; their median age at diagnosis was 5 years (interquartile range: 2-11 years). Clinical presentations and laboratory parameters required for diagnosis included fever (98%), splenomegaly (79%), hyperferritinemia (98%), hemophagocytosis (94%), thrombocytopenia (90%), anemia (63%), hypertriglyceridemia (68%), and neutropenia (57%). The 5-year overall survival (OS) rate was 49%. Of 22 patients who had died at the last follow-up, 15 (68%) died within 180 days after diagnosis. In the multivariate analysis, hemoglobin (odds ratio [OR]: 0.564, p = 0.024) and triglyceride (OR: 1.004, p = 0.049) were significantly associated with 180-day mortality. Higher triglyceride levels at diagnosis were related to significantly lower 180-day OS rates (52.9% vs. 86.1%, p = 0.018). CONCLUSION: The overall outcome in our cohort was similar to that reported in some of the largest international cohorts. Hypertriglyceridemia and anemia may be indicative of poor prognoses in pediatric HLH patients independently and may be used to guide treatment strategy formulations for better outcomes.

ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research.

Calcium, the most versatile second messenger, regulates essential biology including crucial cellular events in embryogenesis. We investigated impacts of calcium channels and purinoceptors on neuronal differentiation of normal mouse embryonic stem cells (ESCs), with outcomes being compared to those of in vitro models of Huntington's disease (HD). Intracellular calcium oscillations tracked via real-time fluorescence and luminescence microscopy revealed a significant correlation between calcium transient activity and rhythmic proneuronal transcription factor expression in ESCs stably expressing ASCL-1 or neurogenin-2 promoters fused to luciferase reporter genes. We uncovered that pharmacological manipulation of L-type voltage-gated calcium channels (VGCCs) and purinoceptors induced a two-step process of neuronal differentiation. Specifically, L-type calcium channel-mediated augmentation of spike-like calcium oscillations first promoted stable expression of ASCL-1 in differentiating ESCs, which following P2Y2 purinoceptor activation matured into GABAergic neurons. By contrast, there was neither spike-like calcium oscillations nor responsive P2Y2 receptors in HD-modeling stem cells in vitro. The data shed new light on mechanisms underlying neurogenesis of inhibitory neurons. Moreover, our approach may be tailored to identify pathogenic triggers of other developmental neurological disorders for devising targeted therapies.

Analysis of the Role and Regulation Mechanism of hsa-miR-147b in Lung Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database.

Objective: This study aimed to explore the role and regulatory mechanism of hsa-miR-147b in lung squamous cell carcinoma (LUSC) through The Cancer Genome Atlas (TCGA) database. Methods: The expression and clinical value of miR-147b in LUSC were analyzed in the TCGA database. The target genes of miR-147b were screened via miRWalk 2.0 and verified in TCGA database. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyzed the differential target genes of miR-147b. Kaplan-Meier survival analysis and Cox regression were used to screen the prognosis-related target genes. Results: The expression of miR-147b in LUSC tissues increased, and was associated with poor prognosis, gender, and stage of LUSC patients. The area under the curve (AUC) of miR-147b was 0.8478 by the receiver-operating characteristic curve. There were 428 differentially expressed genes of miR-147b that played a critical role in drug transport, DNA binding, calcium signaling pathway, and Ras signaling pathway through GO and KEGG. PTGIS, SUSD4, ARC, HTR2C, SHISA9, and PLA2G4D were independent risk factors for poor prognosis in LUSC patients. LUSC patients in the high-risk group had a higher risk of death. The time-dependent AUC was 0.673. Conclusions: MiR-147b might be a potential molecular marker for poor prognosis in patients with LUSC.

Novel Span-PEG Multifunctional Ultrasound Contrast Agent Based on CNTs as a Magnetic Targeting Factor and a Drug Carrier.

Based on the targeting of ferroferric oxide (Fe3O4) and the drug-loading property of carbon nanotubes (CNTs), a novel Span-PEG-composited Fe3O4-CNTs-DOX multifunctional ultrasound contrast agent was designed and applied to tumor lesions. In situ liquid phase synthesis was employed to prepare the Fe3O4-CNTs magnetic targeting complex, and the physical method was used to obtain the Fe3O4-CNTs-DOX complex by loading doxorubicin (DOX) onto Fe3O4-CNTs. The targeted drug-loading complex Fe3O4-CNTs-DOX was combined with the membrane material of Span-PEG by the acoustic vibration cavitation method. The maximum tolerance for Span-PEG-composited Fe3O4-CNTs-DOX microbubbles was 450 times higher, which has good safety. The loading rate of DOX in the obtained composite microbubbles was 17.02%. The proliferation inhibition rate of Span-PEG-composited Fe3O4-CNTs-DOX microbubbles on liver cancer SMMC-7721 cells reached 48.3%. Span-PEG-composited Fe3O4-CNTs-DOX microbubbles could significantly enhance ultrasonic imaging and enrich at a specific location under an external magnetic field, and the extended imaging time could ensure the effective observation and diagnosis of lesions.

A Combinatorial Approach with Cerebellar Tonsil Suspension to Treating Symptomatic Chiari Malformation Type I in Adults: A Retrospective Study.

BACKGROUND: Primary Chiari malformations (CMs) are congenital defects of the skull base and brain. Among the 4 CM types, type I (CM-I) occurs most frequently and may cause somatosensorimotor, autonomic and vision symptoms. Presently, posterior fossa decompression alone (PFD) or with duraplasty (PFDD) and cerebellar tonsil (CbT) shrinkage tactics are standard treatments, albeit inherent issues. There has been no report on devising CbT suspension (CTS) to manage CM-I. OBJECTIVES: 1) To design a CTS protocol that can be used with CbT coagulation (CTC) and PFDD; 2) to evaluate the regimen for feasibility, safety, and efficacy in a retrospective study; and 3) to obtain data for planning prospective studies to validate PFDD + CTC + CTS as a novel approach to treating adult CM-I. METHODS: PFDD + CTC + CTS (n = 17), PFDD + CTC (n = 13), and PFDD (n = 12) were performed for 42 adult patients (age range, 18-55 years; female:male = 27:15) following a balanced study design. Neck Disability Index (NDI), Chicago Chiari Outcome Scale (CCOS), and /magnetic resonance imaging/computed tomography were used to determine postsurgery outcomes for approximately 20 months. RESULTS: Comparing to PFDD + CTC or PFDD, patients receiving PFDD + CTC +CTS operation exhibited significantly improved group average NDI (10.72 ± 3.95%; P = 0.007), CbT elevation distance (7.06 ± 2.42 mm; P < 0.001, Kruskal-Wallis test; 55.7 ± 25.4% higher than the presurgery level; P < 0.001, analysis of variance), and syringomyelia syrinx retraction (P = 0.009, analysis of variance). CONCLUSIONS: The PFDD + CTC + CTS regimen appeared to be safe and potentially more efficacious in patients with CM-I evaluated for the period, relative to PFDD + CTC or PFDD treatment. Future prospective studies were warranted.

Lanostane triterpene glycosides from the flowers of Lyonia ovalifolia var. hebecarpa and their antiproliferative activities.

Sixteen lanostane-type triterpene glycosides including eight new ones, named lyonicarposides A-H (1-8), were isolated from the flowers of Lyonia ovalifolia var. hebecarpa (Franch. ex F.B. Forbes & Hemsl.) Chun (Ericaceae). The chemical structures of the new compounds were elucidated by the comprehensive spectroscopic techniques and chemical methods. The Mo2(OAc)4-induced electronic circular dichroism method was used to determine the absolute configurations of C-24 in lyonicarposides A (1), C (3), and E (5). This is the first phytochemical study on the flowers of L. ovalifolia var. hebecarpa. All the isolates were evaluated for their antiproliferative activities against SMMC-7721, HL-60, SW480, MCF-7, and A-549 cell lines. Lyonicarposides A (1) and B (2) showed moderate antiproliferative activities against five cancer cell lines with IC50 values ranging from 12.39 to 28.71 µM. Lyonicarposides C (3) and G (7) and lyonifoloside M (12) selectively inhibited the proliferation of HL-60 and MCF-7 cell lines with IC50 values ranging from 13.03 to 17.71 µM. Interestingly, lyonifoloside L (13) selectively inhibited the proliferation of MCF-7 cell line with an IC50 value of 16.27 µM. Their structure-activity-relationships were discussed.

Physical impacts of PLGA scaffolding on hMSCs: Recovery neurobiology insight for implant design to treat spinal cord injury.

Our earlier work generated a powerful platform technology of polymeric scaffolding of stem cells to investigate and treat the injured or diseased central nervous system. However, the reciprocal sequelae between biophysical properties of the polymer and responses of the stem cell have not been examined in situ in lesioned spinal cords. We postulated that implantable synthetic scaffolds, acting through physical features, might affect donor cell behavior and host tissue remodeling. To test this hypothesis, poly(d,l-lactic-co-glycolic acid) (PLGA) in either low/soft or high/hard rigidity was fabricated for carrying adult human bone marrow mesenchymal stromal stem cells (hMSCs). The construct was transplanted into the epicenter of a rat model of acute T9-10 segmental hemisection to evaluate the effect of PLGA rigidity on the therapeutic potential and fate of hMSCs for neural repair. Compared to controls, only treatment with soft PLGA-scaffolded hMSCs significantly improved sensorimotor function via activation of recovery neurobiology mechanisms. The main benefits included inhibiting neuroinflammation and enhancing tissue protection. Also detected in the treated lesion region were expressions of neurotrophic and anti-inflammatory factors together with proliferation of endogenous neural stem cells, impacts likely derived from hMSCs' functional multipotency maintained by soft PLGA-scaffolding. Conversely, hard rigidity PLGA activated mechanotransduction and mesoderm lineage differentiation of hMSCs that ectopically produced bone, cartilage and muscle markers in neural parenchyma. The findings collectively suggested that the physical texture of polymeric scaffolds should be tailored for sustaining the stemness of hMSCs to constructively interact with the spinal cord for functional restoration.

Functional Multipotency of Stem Cells and Recovery Neurobiology of Injured Spinal Cords.

This invited concise review was written for the special issue of Cell Transplantation to celebrate the 25th anniversary of the American Society for Neural Therapy and Repair (ASNTR). I aimed to present a succinct summary of two interweaved lines of research work carried out by my team members and collaborators over the past decade. Since the middle of the 20th century, biomedical research has been driven overwhelmingly by molecular technology-based focal endeavors. Our investigative undertakings, however, were orchestrated to define and propose novel theoretical frameworks to enhance the field's ability to overcome complex neurological disorders. The effort has engendered two important academic concepts: Functional Multipotency of Stem Cells, and Recovery Neurobiology of Injured Spinal Cords. Establishing these theories was facilitated by academic insight gleaned from stem cell-based multimodal cross-examination studies using tactics of material science, systems neurobiology, glial biology, and neural oncology. It should be emphasized that the collegial environment cultivated by the mission of the ASNTR greatly promoted the efficacy of inter-laboratory collaborations. Notably, our findings have shed new light on fundamentals of stem cell biology and adult mammalian spinal cord neurobiology. Moreover, the novel academic leads have enabled determination of potential therapeutic targets to restore function for spinal cord injury and neurodegenerative diseases.

Functional multipotency of stem cells: Biological traits gleaned from neural progeny studies.

In this review, a stem cell concept, initially defined by the author more than 10 years ago focusing on neural stem cells, has been systematically refined and updated. Relative to the conventional view which touched principally on the totipotency, pluripotentcy and multipotency of cell lineage differentiation (e.g., the ability of neural stem cells to grow into all three types of neural cells), accumulated data obtained by other researchers and my own team promoted me and my colleagues to propose and establish a new biological concept: Functional Multipotency of Stem Cells. The goal is to recognize the biofunctional multipotency of the stem cell to mediate homeostasis during development and adulthood. Under this academic context, an enriched repertoire of signaling, epigenetic and genetic events has been revealed. Such insight has enabled appreciation of the wide range of molecular tactics the stem cell can use at each developmental or adult stage. The multifunctionality allows stem cells to properly migrate, differentiate, and integrate into as well as prepare, influence, and repair the neighboring cells to steer the micro- and macro-environment towards the formation and self-maintenance of a physiological organ and system. It has been demonstrated that embracing this concept of the stem cell's "functional multipotency" is pivotal for correctly, efficiently, and optimally investigating stem cells to advance fundamental biology and therapeutic translation.

Enhanced ultrasound imaging and anti-tumor in vivo properties of Span-polyethylene glycol with folic acid-carbon nanotube-paclitaxel multifunctional microbubbles.

With Span and polyethylene glycol (PEG) as the membrane material, the as-prepared folate-carbon nanotube-paclitaxel (FA-CNT-PTX) complex was added to the reaction system under sound vibration cavitation and Span-PEG with FA-CNT-PTX microbubbles was obtained. The maximum tolerating dose of the obtained composite microbubbles on Kunming mice was determined by acute toxicity test. Utilizing the breast cancer tumor model in the nude mice to assess the anti-tumor activity in vivo, the inhibition effect of the composite microbubbles on tumor growth was analyzed by recording the weight and tumor volume of the nude mice. HE staining observations, the immunohistochemistry method, and TUNEL were, respectively, used to examine the inhibition effect of the composite microbubbles on breast cancer tumors in the nude mice. The ultrasound imaging effects and the changes in the peak intensities of the composite microbubbles were inspected using a Doppler color ultrasound imaging system. The experimental results showed that the maximum tolerated dose of the composite microbubbles was 3500 mg kg-1, indicating that the composite microbubbles had low toxicity and good biocompatibility. The composite microbubbles could reach the breast cancer tumor via a targeting factor, and then hindered the tumor growth by inhibiting the proliferation of tumor cells and inducing apoptosis of the tumor cells. The composite microbubbles contributed toward enhancing the ultrasound signal and improved the resolution of the ultrasound images and extended the imaging time. Also, the addition of CNTs in the composite microbubbles could enhance the ultrasound contrast. Simultaneously, the peak intensity at the tumor was significantly reduced after the treatment.

Spinal cord astrocytomas: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies.

Spinal cord astrocytomas (SCAs) have discernibly unique signatures in regards to epidemiology, clinical oncological features, genetic markers, pathophysiology, and research and therapeutic challenges. Overall, there are presently very limited clinical management options for high grade SCAs despite progresses made in validating key molecular markers and standardizing tumor classification. The endeavors were aimed to improve diagnosis, therapy design and prognosis assessment, as well as to define more effective oncolytic targets. Efficacious treatment for high grade SCAs still remains an unmet medical demand. This review is therefore focused on research state updates that have been made upon analyzing clinical characteristics, diagnostic classification, genetic and molecular features, tumor initiation cell biology, and current management options for SCAs. Particular emphasis was given to basic and translational research endeavors targeting SCAs, including establishment of experimental models, exploration of unique profiles of SCA stem cell-like tumor survival cells, characterization of special requirements for effective therapeutic delivery into the spinal cord, and development of donor stem cell-based gene-directed enzyme prodrug therapy. We concluded that precise understanding of molecular oncology, tumor survival mechanisms (e.g., drug resistance, metastasis, and cancer stem cells/tumor survival cells), and principles of Recovery Neurobiology can help to create clinically meaningful experimental models of SCAs. Establishment of such systems will expedite the discovery of efficacious therapies that not only kill tumor cells but simultaneously preserve and improve residual neural function.

An ioMRI-assisted case of cervical intramedullary diffuse glioma resection.

PURPOSE: To date, application of intraoperative magnetic resonance imaging (ioMRI) to enhance surgical quality for spinal intramedullary neoplastic lesions has been rarely reported. Moreover, in developing countries or regions, ioMRI accessibility remains very limited. This report describes a technology design of high-field ioMRI accessible for multioperation rooms via a case presentation of an imaging-assisted surgical excision of human cervical spinal cord diffuse glioma. PATIENT AND METHODS: The patient was a 44-year-old woman with symptomatic and progressive C2-5 intramedullary diffuse glioma (IDG). Our ioMRI system was designed and arranged with accessibility to multiple operation rooms, which was used to assure more complete spinal cord or brain tumor removal. The intraoperational diagnostic aspects and the system setup technical details are presented for future applications of the system in hospitals where a designated ioMRI suite is not available. RESULTS: After a conventionally defined complete removal of C2-C5 IDG using a well-established surgical approach, ioMRI examination was able to detect residual tumor tissues that were indistinguishable under the surgical microscope. The IDG clusters were subsequently excised. The operation regimen resulted in a gross total elimination of the tumor, which enabled the patient to show very satisfactory postsurgery recovery and prognosis. CONCLUSION: ioMRI-assisted surgical removal of cervical spinal cord diffuse glioma should be systematically developed and applied to enhance therapeutic efficacy. The reported logistic flow of operating room tasks and imaging technical management are innovative for performing the tumor removal procedures in hospitals where designated ioMRI surgical suites do not exist. Critically, we emphasize implementation of stringent quality control measures for patient transportation safety and contamination prevention in establishing and maintaining such a system.

Cancer Stem Cells or Tumor Survival Cells?

Research endeavors originally generated stem cell definitions for the purpose of describing normally sustainable developmental and tissue turnover processes in various species, including humans. The notion of investigating cells that possess a vague capacity of "stamm (phylum)" can be traced back to the late 19th century, mainly concentrating on cells that could produce the germline or the entire blood system. Lately, such undertakings have been recapitulated for oncogenesis, tumor growth, and cancer cell resistance to oncolytic therapies. However, due to the complexity and basic life-origin mechanisms comprising the genetic and epigenetic repertoire of the stemness in every developing or growing cell, presently there are ongoing debates regarding the biological essentials of the stem cell-like tumor initiation cells (ie, cancer stem cells; CSCs). This conceptual analysis focuses on the potential pitfalls of extrapolating that CSCs bear major traits of stemness. We propose a novel nomenclature of Tumor Survival Cells (TSCs) to further define tumor cells behaving like CSCs, based on the ruthless and detrimental features of Cancer Cell Survivology that appears fundamentally different from stem cell biology. Hence, precise academic separation of TSCs from all the stem cell-related labels applied to these unique tumor cells may help to improve scientific reasoning and strategies to decode the desperado-like survival behaviors of TSCs to eventually overcome cancer.