Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Serotonin receptor HTR2B facilitates colorectal cancer metastasis via CREB1-ZEB1 axis mediated epithelial-mesenchymal transition.

A number of neurotransmitters have been detected in tumor microenvironment and proved to modulate cancer oncogenesis and progression. We previously found that biosynthesis and secretion of neurotransmitter 5-hydroxytryptamine (5-HT) was elevated in colorectal cancer (CRC) cells. In this study, we discovered that the HTR2B receptor of 5-HT was highly expressed in CRC tumor tissues, which was further identified as a strong risk factor for CRC prognostic outcomes. Both pharmacological blocking and genetic knocking down HTR2B impaired migration of CRC cell, as well as the epithelial-mesenchymal transition (EMT) process. Mechanistically, HTR2B signaling induced ribosomal protein S6 kinase B1 (S6K1) activation via Akt/mTOR pathway, which triggered cAMP responsive element binding protein 1 (CREB1) phosphorylation (Ser 133) and translocation into the nucleus, then the phosphorylated CREB1 acts as an activator for ZEB1 transcription after binding to CREB1 half-site (GTCA) at ZEB1 promoter. As a key regulator of EMT, ZEB1 therefore enhances migration and EMT process in CRC cells. We also found that HTR2B specific antagonist (RS127445) treatment significantly ameliorated metastasis and reversed EMT process in both HCT116 cell tail-vein-injected pulmonary metastasis and CT26 cell intrasplenic-injected hepatic metastasis mouse models. Implications: These findings uncover a novel regulatory role of HTR2B signaling on CRC metastasis, which provide experimental evidences for potential HTR2B-targeted anti-CRC metastasis therapy.

Thoracic endovascular aortic repair under venoarterial extracorporeal membrane oxygenation for acute aortic dissection patients: a case report.

Background: Open repair and replacement of the diseased aorta is still the standard treatment for type A aortic dissection (TAAD) in most patients. In endovascular treatment alone, ensuring adequate blood supply to the brain while covering the dissection with a stent is difficult. Case presentation: This study includes a 71-year-old male patient with type A aortic dissection presented at a recent follow-up examination after having undergone thoracic endovascular aortic repair (TEVAR) plus left subclavian artery chimney stent reconstruction for descending aortic dissection 5 years ago. Preoperative computed tomographic angiography, computed tomographic perfusion, and transcranial Doppler showed an intact cerebral arterial ring and good collateral circulation. We successfully performed an endovascular repair of the thoracic aorta with venoarterial extracorporeal membrane oxygenation (V-A ECMO) to protect the craniocerebral blood supply, greatly increase the safety of the operation, and ensure a good prognosis. Conclusion: TEVAR under V-A ECMO protection is beneficial for patients with TAAD because of its minimal trauma, rapid recovery, few complications, and low mortality.

Combined Use of Immune Checkpoint Inhibitors and Phytochemicals as a Novel Therapeutic Strategy against Cancer.

Immune checkpoint inhibitor (ICI) therapy has dramatically changed cancer treatment, opening novel opportunities to cure malignant diseases. To date, most prevalently targeted immune checkpoints are programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with many others being under extensive investigations. However, according to available data, only a fraction of patients may respond to ICI therapy. Additionally, this therapy may cause severe adverse immune-related side effects, such as diarrhea, headache, muscle weakness, rash, hepatitis and leucopenia, although most of them are not fatal, they can affect the patient's treatment outcome and quality of life. On the other hand, growing evidence has shown that phytochemicals with anticancer effects may combine ICI therapy to augment the safety and effectiveness of the treatment against cancer while reducing the adverse side effects. In this review, we summarize the state of art in the various experiments and clinical application of ICIs plus phytochemicals, with a focus on their combined use as a novel therapeutic strategy to cure cancer.

FAM117B promotes gastric cancer growth and drug resistance by targeting the KEAP1/NRF2 signaling pathway.

Gastric cancer often shows malignant growth and insensitivity to chemotherapeutic drugs due to the regulation of complex molecular mechanisms, which results in poor prognosis for patients. However, the relevant molecular mechanisms remain unclear. In this study, we reported that family with sequence similarity 117, member B (FAM117B), promoted the growth of gastric cancer cells and reduced the sensitivity of cells to chemotherapeutic drugs. Mechanistically, FAM117B competed with nuclear factor E2-related factor 2 (NRF2) for Kelch-like ECH-associated protein 1 (KEAP1) binding, reduced the ubiquitination degradation of NRF2, and activated the KEAP1/NRF2 signaling pathway. Moreover, FAM117B-induced growth and chemoresistance of gastric cancer cells were NRF2 dependent. We found that FAM117B and NRF2 protein levels were highly expressed in tumor tissues of patients with gastric cancer and their co-overexpression represented an independent factor for poor prognosis. Collectively, our findings reveal that FAM117B is involved in promoting gastric cancer growth and drug resistance, and it could be exploited as a cancer therapeutic target.

Femoral artery variation was found during V-A ECMO catheterization.

BACKGROUND: High bifurcation of the deep femoral artery (DFA) is rare in clinical practice, and patients with this variation are less likely to receive venoarterial extracorporeal membrane oxygenation (V-A ECMO) treatment. Therefore, the method by which V-A ECMO is introduced in patients with vascular variation is very important. CASE PRESENTATION: A 52-year-old male patient had ST elevation myocardial infarction due to coronary heart disease. Angiography showed tripartite coronary artery lesions, and coronary artery stenting supported by V-A ECMO was needed. Vascular evaluation before ECMO catheterization revealed high bifurcation of the bilateral DFA located at the inguinal ligament. After discussion, the perfusion cannula was placed in the left superficial femoral artery (SFA) towards the heart, and the distal perfusion catheter (DPC) was placed in the left SFA towards the distal end. Nevertheless, after the patient's heart recovered, necrosis of the toe of the left lower limb still occurred. CONCLUSION: Common femoral artery assessment must be performed before V-A ECMO for patients with high bifurcation of the DFA. Incision catheterization and DPC placement are recommended. After decannulation, arterial repair under direct visualisation is recommended, and rigorous distal vascular assessment and management are needed.

Naringenin suppresses epithelial ovarian cancer by inhibiting proliferation and modulating gut microbiota.

BACKGROUND: Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown. PURPOSE: This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms. METHODS: Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing. RESULTS: Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus. CONCLUSION: Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.

The Clinical Noteworthiness of Plasma NT-ProBNP Standard in Sufferers with Cardiogenic Cerebral Embolism and Its Diagnostic Value for Such Sufferers.

In order to explore the clinical noteworthiness of plasma NT-proBNP standards in sufferers with cardiogenic cerebral embolism and its diagnostic value for such sufferers, a retrospective study is conducted by the clinical data of sufferers with cerebral embolism. 100 sufferers with cerebral embolism admitted to our hospital from January 2018 to December 2020 are selected. According to the heparin-like drug therapy of acute ischemic stroke test (TOAST) classification criteria, they are divided into cardiac sufferers with cerebral embolism set (43 cases) and noncardiac cerebral embolism set (57 cases). The analysis results show the correlation between serum NT-proBNP standard and neurological impairment score. The detection of-proBNP standard can be used as a diagnostic indicator of disease severity and prognosis for sufferers with cardiogenic cerebral embolism.

Trabectedin in Cancers: Mechanisms and Clinical Applications.

Trabectedin, a tetrahydroisoquinoline alkaloid, is the first marine antineoplastic agent approved with special anticancer mechanisms involving DNA binding, DNA repair pathways, transcription regulation and regulation of the tumor microenvironment. It has favorable clinical applications, especially for the treatment of patients with advanced soft tissue sarcoma, who failed in anthracyclines and ifosfamide therapy or could not receive these agents. Currently, trabectedin monotherapy regimen and regimens of combined therapy with other agents are both widely used for the treatment of malignancies, including soft tissue sarcomas, ovarian cancer, breast cancer, and non-small-cell lung cancer. In this review, we have summarized the basic information and some updated knowledge on trabectedin, including its molecular structure, metabolism in various cancers, pharmaceutical mechanisms, clinical applications, drug combination, and adverse reactions, along with prospects of its possibly more optimal use in cancer treatment.

MALAT1 regulates PCT expression in sepsis patients through the miR-125b/STAT3 axis.

BACKGROUND: Procalcitonin (PCT) is an important marker in diagnosing sepsis. However, some other diseases can also cause an increase in PCT. PCT still has some limitations in the clinical application of diagnosing sepsis. Therefore, it is of great significance to clarify the regulatory mechanism of PCT expression in sepsis and provide new therapeutic targets for sepsis. METHODS: Blood samples from clinical patients were collected, and peripheral blood monocytes were isolated. Bioinformatics was performed to find the ceRNA regulatory network of STAT3/PCT. MALAT1 and miR-125b were detected by qRT-PCR. MALAT1 was located by fluorescence in situ hybridization (FISH) in U937 cells, and the regulatory relationship between MALAT1, miR-125b, and STAT3 was verified by double luciferase activity report and RNA pull-down assay. U937 cells were transfected with miR-125b, and the effects of the MALAT1/miR-125b/STAT3 pathway on gene and protein secretion levels of PCT were verified by qRT-PCR, western blot, and ELISA. RESULTS: In the serum of sepsis patients and lipopolysaccharide(LPS)-induced U937 cells, MALAT1, STAT3, and PCT gene expression levels were significantly increased, while miR-125b expression level was decreased. FISH results showed that the MALAT1 transcript was mainly located in the nucleus. The double luciferase activity report and RNA pull-down assay results suggested a targeted regulatory relationship between MALAT1, miR-125b, and STAT3. LPS-induced U937 cells transfection with MALAT1 siRNA decreased STAT3 protein expression and phosphorylation level and the expression of PCT. Co-transfection with miR-125b inhibitor effectively reversed this phenomenon. CONCLUSIONS: MALAT1 could upregulate the expressions of STAT3 and PCT by targeted adsorption of miR-125b.

Early versus Delayed Minimally Invasive Intervention for Acute Necrotizing Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Nowadays, minimally invasive intervention (MII) has largely replaced delayed open surgery in acute necrotizing pancreatitis (ANP). However, the timing of MII remains unclear. The present study investigated the effect of early versus delayed MII on complications in ANP. METHODS: Studies evaluating the impact of the timing of MII on complications in ANP patients were thoroughly searched on PubMed, Embase, Cochrane Library, and Web of Science from inception to June 2022. The primary outcome of interest was mortality. Secondary outcomes were the incidence of complications. RESULTS: Nine studies reporting 870 patients undergoing MII for ANP were included. No significant difference was found in mortality between the early and delayed intervention groups. In addition, the timing of MII was not associated with the incidence of new-onset respiratory failure, new-onset cardiovascular failure, new-onset renal failure, new-onset multiple organ failure, gastrointestinal fistula or perforation, pancreatic fistula, stent migration, bleeding, venous thrombosis, and new-onset pancreatic endocrine insufficiency. Notably, in the subgroup analysis of biliary and Asian ANP patients, early intervention was associated with a significantly higher risk of new-onset renal failure than delayed intervention. CONCLUSIONS: Early intervention is safe and recommended only for patients with indications for intervention, such as infection.

Evaluation of glycemic index, antioxidant capacity, and metabolic effects of a fermented beverage made from Changbai Mountain fruit and vegetables.

Fermented foods and beverages have been known to be beneficial when included in the human diet. This study examined the glycemic index (GI) of a fermented beverage (FB) made from Changbai Mountain fruit and vegetables in humans and its antioxidant capacity and metabolic effects in a rat model of diabetes. Twenty healthy volunteers were tested with 50 g of glucose and 50 g equivalent of carbohydrates from FB on two separate days for GI measurement. The rats were randomly divided into blank control group (n = 15) and diabetic model (DM) group (n = 75). DM group were randomly divided into five groups, positive control group, model control group and three FB treatment (2.5, 5, 10 ml/kg·bw·d) groups. The general indices, including blood glucose and lipid levels and antioxidant index, of the rats were measured to investigate the effect of FB. The GI of FB was found to be 56.99, indicating it as a medium GI food. Compared to model control group, the low-dose FB group had lower blood glucose levels and higher high-density lipoprotein cholesterol levels in DM rats (p < .05). Medium- and high-dose FB decreased the serum malonaldehyde levels in DM rats compared to those in the model control group. The FB-treated DM rat groups showed increased serum glutathione and superoxide dismutase levels compared with those in the model control group (p < .05). FB is a medium GI food that plays a protective role against oxidative stress in DM rats. PRACTICAL APPLICATIONS: The present study evaluated the glycemic index of a fermented beverage (FB) made from Changbai Mountain fruit and vegetables in humans and investigated its antioxidant capacity and metabolic effects in a rat diabetes model. The study results may aid in the development of FB from fruits and vegetables and provide a theoretical basis for further research and development.

Using EEG and MEG to characterize extreme delta brush in a patient with anti-NMDA receptor encephalitis.

BACKGROUND: Extreme delta brush (EDB) is considered a potential marker for anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The brain regions involved in EDB are unclear. CASE PRESENTATION: A 16-year-old woman with anti-NMDAR encephalitis who was experiencing psychosis was admitted. Electroencephalography (EEG) and magnetoencephalography (MEG) were used to analyze EDB in the patient. EDB on EEG could be disturbed by opening and closing the eyes, by occipital alpha rhythms and by sleep-wake cycles. The MEG results showed beta activity originating from bilateral superior parietal lobes. However, the delta wave originated from bilateral superior temporal gyri, the right middle temporal gyrus, the right inferior frontal gyrus, and the left inferior parietal lobe. CONCLUSIONS: Delta wave and beta activity might originate from different brain regions. Beta activity might be transmitted forward to the frontotemporal lobe and superimposed with delta activity to form EDB on EEG.

Clinical Features and Prognosis in Chinese Patients With Dipeptidyl-Peptidase-Like Protein 6 Antibody-Associated Encephalitis.

OBJECTIVES: Anti-dipeptidyl-peptidase-like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis. METHODS: Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed. RESULTS: All five patients were male. The media age at disease onset was 32 years old with a range of 14-56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients. CONCLUSIONS: Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement.

Influencing electroclinical features and prognostic factors in patients with anti-NMDAR encephalitis: a cohort follow-up study in Chinese patients.

The clinical manifestations of patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in East China and factors associated with prognosis were analyzed. A retrospective study of 106 patients (58 females; 48 males) with anti-NMDAR encephalitis in East China was carried out from June 2015 to February 2019. Clinical features and factors influencing outcomes were reviewed. Behavioral changes were observed in 74.5% (79/106) of patients, and comprised the initial symptoms in 61.3% (65/106). Seizures were observed in 67% (71/106) of patients, and served as initial symptoms in 31.1% (33/106). A total of 54.9% (39/71) of seizures were focal seizures. More clinical symptoms were observed in female patients than in male patients (P = 0.000). Similarly, background activity (BA) with high cerebrospinal fluid (CSF) antibody titers at the peak stage was more severe in female patients than in male patients (P = 0.000). The Binary logistic regression and receiver operating characteristic (ROC) curve analyses revealed the factors associated with poor outcomes included consciousness disturbance (OR 4.907, 95% CI 1.653-14.562, P = 0.004; area: 65.4%, sensitivity: 44.2%, specificity: 86.5%, P = 0.014), EEG BA (OR 3.743, 95% CI 1.766-7.932, P = 0.001; area: 76.6%, sensitivity: 73%, specificity: 75%, P = 0.000), number of symptoms (OR 2.911, 95% CI 1.811-4.679, P = 0.000; area: 77.1%, sensitivity: 59.5%, specificity: 78.6%, P = 0.000) and CSF antibody titer (OR 31.778, 95% CI 8.891-113.57, P = 0.000; area: 83.9%, sensitivity: 89.2%, specificity: 78.6%, P = 0.000). EEG BA and number of symptoms were associated with CSF antibody titers. Consciousness disturbances, EEG BA, number of symptoms and CSF antibody titers served as predictors of poor outcomes.

Effects of a Fermented Beverage of Changbai Mountain Fruit and Vegetables on the Composition of Gut Microbiota in Mice.

Evidence suggests that fermented foods and beverages made from fruits and vegetables benefit human health, including in the prevention of cardiovascular disease, cancer, diabetes and gastrointestinal disorders. However, there are few studies on the effects of fermented fruits and vegetables on intestinal microbiota. In this study, we investigated the changes in the composition of the intestinal microbial community after short-term treatment with a fermented beverage of Changbai Mountain fruit and vegetables (FB). Forty male ICR mice, weighing 17-19 g, were fed diets with different concentrations of the FB or distilled water for 15 days. 16S rDNA gene sequences were used to analyze the gut microbiota with the Illumina sequencing platform and a paired-end method. FB had no effect on weight gain, the adiposity index, or food intake in the treated mice compared with the control group. The cecal index was significantly higher in the FB-administered groups than in the control group. Firmicutes and Bacteroidetes were the dominant phyla in the mice ceca. The Firmicutes/Bacteroidetes ratio was reduced in the FB-administered mice, and proportions of the family Prevotellaceae, Bacteroidales_S24-7_group, family Bacteroidaceae, and genus Bacteroides increased, and these increases were correlated positively with intake of fermented beverage. The FB also altered the diversity of the cecal microbiota in the mice. Graphical Abstract.

[Direct quantitative analysis of amino acids in fermented beverage of plant extract using high performance liquid chromatography-tandem mass spectrometry].

A method was established for underivatized amino acid determination in fermented beverage of plant extract. Samples were diluted with methanol for five times, extracted by ultrasonic vibration for 30 min, and high-speed centrifuged for 15 min at 10,000 r/min. The supernatant was separated and detected by, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The chromatographic column was Venusil ASB C18 (250 mm x 4.6 mm, 5 µm). The elution was performed at a flow rate of 0.5 mL/min using the mobile phases of methanol-acetic acid-water mixture. The MS detector was set as follows: ion source voltage 3 kV, ion source temperature 150 t, solvent temperature 350 t, gas flow rate 800 L/h. The collision gas was argon with a pressure of 0.17 Pa. The quantitation analysis was carried out with peak area in extracted ion chromatograms. Good linearities were acquired in the range of 0.5-200 µmol/L (r2 > 0.99) for the amino acids. The recoveries were between 86% and 110%. There were 16 amino acids in the fermented beverage of plant extract quantitatively analyzed. The method is simple, rapid, accurate and reliable in quantitative analysis of amino acid samples in the fields of pharmaceutical, food and natural products.