(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.

Antitumor activity of galaxamide involved in cell apoptosis and stemness by inhibiting Wnt/ß-catenin pathway in cervical cancer.

Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. In this study, the growth-inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. It was found galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signaling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness by Wnt6 signaling pathway in HeLa cells. By analyzing The Cancer Genome Atlas database, Wnt6 was found to be negatively/positively correlated with stemness- and apoptosis-related genes in human cervical cancer. Cancer stem-like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and ß-catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere-forming ability, along with inhibition of stemness-related and Wnt pathway genes. Galaxamide treatment was also accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Our results provide evidence that suppression of stemness by downregulating the Wnt signaling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.

Spongimides A and B, two new alkaloids from the marine sponge Spongia sp.

Two new alkaloids, spongimides A (1) and B (2), along with five known ones (3-7), were isolated from the marine sponge Spongia sp. The structures of 1 and 2 were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compounds 1, 3, and 4 were the first examples of 2,4-imidazolidinediones isolated from this genus. In addition, the cytotoxic and antibacterial activities of compounds 1 and 2 were also evaluated.

Intraoperative incision irrigation with high-volume saline reduces surgical site infection for abdominal infections.

Purpose: Surgical site infection (SSI) remains one of the most common postoperative complications for patients with abdominal infections. This study aimed at investigating the effectiveness of high-volume normal saline (NS) irrigation in preventing postoperative SSI for patients with abdominal infections. Methods: In this retrospective before-after clinical study, patients who underwent emergency laparotomy due to abdominal infections between Jan 2015 and Dec 2021 were included consecutively. A cohort of 207 patients with NS irrigation was compared to historical controls. A propensity score matching (PSM) with a 1:1 ratio was performed to reduce potential bias. The primary outcome was the 30-day SSI rate. Results: Irrigation (n = 207) and control (n = 207) matched patients were statistically identical on baseline characteristics, perioperative, and intraoperative parameters. Irrigation patients had lower overall SSI rates (10.6% vs. 26.1%, p < 0.001), mainly due to reduction in superficial (4.3% vs. 17.9%) and deep (1.4% vs. 3.9%) SSIs, rather than space/organ SSIs (4.8% vs. 4.3%). Irrigation patients also had lower rates of incision seroma (4.8% vs. 11.6%, p = 0.012), shorter duration of antibiotics use (5.2 ± 1.7 d vs. 7.2 ± 2.0 d, p < 0.001), and unplanned readmission (1.0% vs. 8.7%, p < 0.001). Length of hospital stay showed a declining trend with irrigation intervention, while no significant difference was observed. Moreoever, logistic regression revealed that NS irrigationwas an independent protector against SSI (OR 0.309; 95% CI, 0.207-0.462; p < 0.001). Conclusion: Intraoperative incision irrigation with high-volume NS is associated with a lower rate of SSI for patients with abdominal infections.

Synthesis of Marine Cyclopeptide Galaxamide Analogues as Potential Anticancer Agents.

In this paper, eight new galaxamide analogues (Z-1~Z-8) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue Z-6 displayed broad spectrum cytotoxic activity toward each tested cell line with IC50 values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) µg/mL, respectively. The galaxamides Z-3 and Z-6 induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells.

Molecular and Clinical Characterization of LIGHT/TNFSF14 Expression at Transcriptional Level via 998 Samples With Brain Glioma.

LIGHT, also termed TNFSF14, has been reported to play a vital role in different tumors. However, its role in glioma remains unknown. This study is aimed at unveiling the characterization of the transcriptional expression profiling of LIGHT in glioma. We selected 301 glioma patients with mRNA microarray data from the CGGA dataset and 697 glioma patients with RNAseq data from the TCGA dataset. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analyses and figure generation were performed with R language. LIGHT expression showed a positive correlation with WHO grade of glioma. LIGHT was significantly increased in mesenchymal molecular subtype. Gene Ontology analysis demonstrated that LIGHT was profoundly involved in immune response. Moreover, LIGHT was found to be synergistic with various immune checkpoint members, especially HVEM, PD1/PD-L1 pathway, TIM3, and B7-H3. To get further understanding of LIGHT-related immune response, we put LIGHT together with seven immune signatures into GSVA and found that LIGHT was particularly correlated with HCK, LCK, and MHC-II in both datasets, suggesting a robust correlation between LIGHT and activities of macrophages, T-cells, and antigen-presenting cells (APCs). Finally, higher LIGHT indicated significantly shorter survival for glioma patients. Cox regression models revealed that LIGHT expression was an independent variable for predicting survival. In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.

BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma.

Bradykinin receptor B2 (BDKRB2) has been reported as an oncogene in several malignancies. In glioma, the role of BDKRB2 remains unknown. This study aimed at investigating its clinical significance and biological function in glioma at the transcriptional level. We selected 301 glioma patients with microarray data from CGGA database and 697 with RNAseq data from TCGA database. Transcriptome and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. BDKRB2 expression showed a positive correlation with the WHO grade of glioma. BDKRB2 was increased in IDH wildtype and mesenchymal subtype of glioma. Gene ontology analysis demonstrated that BDKRB2 was profoundly associated with extracellular matrix organization in glioma. GSEA analysis revealed that BDKRB2 was particularly correlated with epithelial-to-mesenchymal transition (EMT). GSVA analysis showed that BDKRB2 was significantly paralleled with several EMT signaling pathways, including PI3K/AKT, hypoxia, and TGF-ß. Moreover, BDKRB2 expression was significantly correlated with key biomarkers of EMT, especially with N-cadherin, snail, slug, vimentin, TWIST1, and TWIST2. Finally, higher BDKRB2 indicated significantly shorter survival for glioma patients. In conclusion, BDKRB2 was associated with more aggressive phenotypes of gliomas. Furthermore, BDKRB2 was involved in the EMT process and could serve as an independent prognosticator in glioma.

Gentamycin irrigation significantly reduces 28-day surgical site infection after emergency neurosurgery.

OBJECTIVE: This study aims to evaluate the effectiveness of gentamycin irrigation in preventing postoperative surgical site infection (SSI) in emergency neurosurgical procedures. METHODS: A total of 518 consecutive emergency neurosurgeries, including craniotomies, endoscopic and burr hole procedures were reviewed retrospectively. Patients received either only normal saline (NS) irrigation or NS irrigation with gentamycin added (80 mg/L) during the whole process of surgery. SSIs including wound infection and intracranial infection were the primary outcome. SSI was considered while purulence was observed during wound dressing and confirmed with bacterial culture of wound exudation. In addition, positive result of bacterial growth culture of cerebrospinal fluid was also considered as infection. Infection rates were calculated 28 days after surgery. Statistical analysis was performed using t test or Chi-squared test where appropriate. RESULTS: This study included 444 patients. Gentamycin was used in 179 (40.3%) patients. Only 2 (1.1%) of 179 patients receiving gentamycin irrigation had an infection. However, among the other 265 patients receiving only NS irrigation, the infection rate was 8.3%. With the addition of gentamycin, the infection rate was decreased by 86.7% (P = 0.001). The two infected patients in gentamycin group were compromised postoperatively: one patient had removed his own extraventricular drainage tube accidentally due to restlessness, and the other had severely contaminated his wound with vomitus during the intracranial drainage tube removal process. If these two patients were excluded from analysis, the effective infection rate using gentamycin irrigation is 0%. CONCLUSION: The gentamycin plus NS irrigation during emergency neurosurgical procedures can lead to a significantly lower rate of postoperative infection than when NS is used alone.

IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma.

BACKGROUND: In cancer, kappa B-interacting protein (IKBIP) has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at the transcriptional level. METHODS: We selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptional data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. RESULTS: We found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in isocitrate dehydrogenase (IDH) wild type and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent gene set enrichment analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed gene set variation analysis to screen the EMT-related signaling pathways and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-ß pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients. CONCLUSIONS: IKBIP was associated with more aggressive phenotypes of gliomas. Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma.

BACKGROUND: Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. METHODS: Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. RESULTS: CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFß, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. CONCLUSIONS: CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

(+)- and (-)-Spongiterpene, a pair of new valerenane sesquiterpene enantiomers from the marine sponge Spongia Sp.

(+)- and (-)-Spongiterpene [(+)-1 and (-)-1], a pair of new valerenane sesquiterpene enantiomers, along with four known compounds (2-5) were isolated from the marine sponge Spongia sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis, quantum chemical calculation and X-ray diffraction. Compounds (+)-1 and (-)-1 were the first examples of valerenane sesquiterpenes isolated from the marine sponges. The cytotoxic activities of (+)-1 and (-)-1 were also evaluated.

The risk factors for the postoperative pulmonary infection in patients with hypertensive cerebral hemorrhage: A retrospective analysis.

ABSTRACT: The risk factors for the pulmonary infections after hypertensive cerebral hemorrhage remains unclear. We aimed to investigate the potential risk factors for the postoperative pulmonary infection in patients with hypertensive cerebral hemorrhage.Patients with hypertensive cerebral hemorrhage undergone surgery from January 2018 to December 2019 were included. Related personal and medical information were collected. Univariate and multivariate logistic regression analyses were performed to identify the potential risk factors for the postoperative pulmonary infection.A total of 264 patients were included, and the incidence of pulmonary infection for patients with hypertensive cerebral hemorrhage after surgery was 19.70%. Escherichia coli is the most common bacteria of pulmonary infection. Multivariate regression analysis revealed that the preoperative hypoalbuminemia (OR2.89, 1.67∼4.78), tracheotomy (OR5.31, 1.24∼11.79), diabetes (OR4.92, 1.32∼9.80), preoperative GCS (OR5.66, 2.84∼11.21), and the duration of mechanical ventilation (OR2.78, 2.32∼3.61) were the independent risk factors for the pulmonary infection in patients with hypertensive cerebral hemorrhage (all P < .05).Patients with hypertensive intracerebral hemorrhage after surgery have a higher risk of postoperative pulmonary infections, and there are many related risk factors, which should be taken seriously in clinical practice.

Severe tetanus following ulcerated skin cancer: Case report.

RATIONALE: Tetanus is usually caused by wound infection with Clostridium tetani after acute injuries. Skin cancer wound is a rarely reported cause of tetani infection. It is difficult to be diagnosed and mistaken for other brain lesions. PATIENT CONCERNS: A 49-year-old man presenting with the only symptom of repeated convulsions was admitted to our department. He had an ulcerated skin cancer on the right buttock that had been excised in another hospital 1 month before admission, leaving the wound unhealed. He was suspected of having a metastatic brain tumor early, but exhibited a negative cranial CT-scan. DIAGNOSIS: Tetanus was diagnosed when he was observed to have sudden convulsions after sensory stimulation such as noise, light, or touch. INTERVENTIONS: Despite administration of a high dose of diazepam and phenobarbitone, continuous generalized rigidity with laryngospasm still occurred. Instead, when propofol was intravenously infused, the spastic convulsion completely stopped. Tracheotomy and mechanical ventilation were performed. OUTCOMES: The patient gradually recovered in 2 weeks. LESSONS: Tetanus is rarely infected through the wound of an ulcerated skin cancer. Early diagnosis can only be based on accurate assessment of clinical manifestations, and propofol infusion appears to be more effective in anti-convulsion management for patients with tetanus. Routine vaccination to prevent tetanus in patients with ulcerated skin cancer should be considered in the future clinical work.

Uridine phosphorylase 1 is a novel immune-related target and predicts worse survival in brain glioma.

Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC-II and LCK, which were mainly associated with activities of antigen-presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7-H3. Finally, Kaplan-Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor-related immune response.

New Alkaloids and Polyketides from the Marine Sponge-Derived Fungus Penicillium sp. SCSIO41015.

The sponge-derived fungus Penicillium sp. SCSIO41015 cultured on solid rice medium yielded twenty-one compounds (1-21), including two new alkaloids (1 and 2) and one new pyrone derivative (3). Their structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. Their absolute configurations were established by single-crystal X-ray diffraction analysis and comparison of the experimental with reported specific rotation values. Compound 16 exhibited selective cytotoxic activity against the human gastric cancer cells MGC803, with IC50 value of 5.19 µM. Compounds 9 and 18 showed weak antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, respectively, both with MIC values of 57 µg/mL. Furthermore, compound 16 displayed potent antibacterial activity against S. aureus with an MIC value of 3.75 µg/mL.

Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells.

Four neoantimycins H-K (1-4) with C1-keto, including the new ones (1-2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5-8) in vitro, the absolute structures of 1-8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.

Sinulaspirolactam A, a novel aza-spirocyclic valerenane sesquiterpenoid from soft coral Sinularia sp.

A novel valerenane sesquiterpenoid sinulaspirolactam A (1), together with five known compounds, was isolated from the soft coral Sinularia sp. Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by ECD calculation. Compound 1 was the first example of valerenane sesquiterpenoid bearing an aza-spiro[4.5] ring moiety, the plausible biogenetic pathway of which was proposed. Cytotoxic activities of these compounds were also evaluated.

Marine Natural Product Bis-indole Alkaloid Caulerpin: Chemistry and Biology.

Marine bis-indole alkaloids comprise a large and increasingly growing class of secondary metabolites, and continue to deliver a great variety of structural templates for diverse biological targets. The alkaloids derived from marine resources play a crucial role in medicinal chemistry and as chemical agents. In particular, bis-indole alkaloid caulerpin which has been isolated from marine green algae Caulerpa and a red algae Chondria armata at various places around the world, was tested for several therapeutic potentials such as anti-diabetic, antinociceptive, anti-inflammatory, anti-tumor, anti- larvicidal, anti-herpes, anti-tubercular, anti-microbial and immunostimulating activities as well as a means of other chemical agents. Herein, we summarized the discovery and isolation of caulerpin, and its potential medicinal and chemical applications in chronological order with various aspects. Additionally, synthesis of caulerpin and its functional analogues have also been reviewed.

Two new steroids with cytotoxicity from the marine sponge Dactylospongia elegans collected from the South China Sea.

A new steroid, (3S,5R,9R,10S,13R,17R,20R,24S,22E)-ergosta-6,8,22-triene-3,25-diol (1), and its sulfonated analogue (2) together with a known one, 5α,8α-epidioxy-cholest-6-en-3ß-ol (3) were isolated from the marine sponge Dactylospongia elegans collected from the South China Sea. The new structures including absolute configurations were established by the HRESIMS and 1D and 2D NMR analysis coupled with the X-ray crystal analysis. Both of 1 and 2 exhibited cytotoxicity against cancer cell line MCF-7 with IC50 values of 9.7 and 8.5 µM, respectively.

Unusual anti-inflammatory meroterpenoids from the marine sponge Dactylospongia sp.

Five new sesquiterpene hydroquinones, dactylospongins A-D (1-4) and 19-O-methylpelorol (10), as well as four new sesquiterpene quinones, melemeleones C-E (6-8) and dysidaminone N (9), were isolated from the marine sponge Dactylospongia sp. collected from the South China Sea, along with five known analogues, ent-melemeleone B (5), pelorol (11), 17-O-acetylavarol (12), 20-O-acetylavarol (13), and 20-O-acetylneoavarol (14). The structures were elucidated by spectroscopic data analyses and comparison with the published NMR data, while the absolute configurations of new structures were assigned by comparison between the experimental and calculated ECD spectra. Dactylospongins A (1) and B (2) are the first sesquiterpenoids with a benzothiazole ring from the marine environment. Anti-inflammatory evaluation showed that 1, 2, 4, 5, 9, and 10 showed potent inhibitory effects on the production of inflammatory cytokines (IL-6, IL-1ß, IL-8, and PEG2) in LPS-induced THP-1 cells with IC50 values of 5.1-9.2 µM; however, none of them showed significant effects on the production of MCP-1 and TNF-α. Additionally, 19-O-methylpelorol (10) exhibited cytotoxicity against lung cancer PC-9 cell lines with an IC50 value of 9.2 µM.