Acanthiline A, a pyrido[1,2-a]indole alkaloid from Chinese mangrove Acanthus ilicifolius.

Chemical investigation of the leaves and stems of the Chinese mangrove Acanthus ilicifolius Linn. led to the isolation and structure elucidation of one new pyrido[1,2-a]indole alkaloid named acanthiline A (1), together with one known compound aurantiamide acetate (2). Compound 1 has a previously unreported natural product skeleton. The structure elucidation of 1 was based on the analysis of its 1D and 2D NMR and mass spectroscopic data.

Applications of deep learning for detecting ophthalmic diseases with ultrawide-field fundus images.

AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks. METHODS: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images. RESULTS: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200° in a single exposure, which can observe more areas of the retina. CONCLUSION: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.

Apigenin Ameliorates H2O2-Induced Oxidative Damage in Melanocytes through Nuclear Factor-E2-Related Factor 2 (Nrf2) and Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt)/Mammalian Target of Rapamycin (mTOR) Pathways and Reducing the Generation of Reactive Oxygen Species (ROS) in Zebrafish.

Background: Apigenin is one of the natural flavonoids found mainly in natural plants, as well as some fruits and vegetables, with celery in particular being the most abundant. Apigenin has antioxidant, anti-tumor, anti-inflammatory, and anticancer effects. In this research, we attempted to further investigate the effects of apigenin on the mechanism of repairing oxidative cell damage. The present study hopes to provide a potential candidate for abnormal skin pigmentation disorders. Methods: We used 0.4 mM H2O2 to treat B16F10 cells for 12 h to establish a model of oxidative stress in melanocytes, and then we gave apigenin (0.1~5 µM) to B16F10 cells for 48 h, and detected the expression levels of melanin synthesis-related proteins, dendritic regulation-related proteins, antioxidant signaling pathway- and Nrf2 signaling pathway-related proteins, autophagy, and autophagy-regulated pathways by immunoblotting using Western blotting. The expression levels of PI3K/Akt/mTOR proteins were measured by ß-galactosidase staining and Western blotting for cellular decay, JC-1 staining for mitochondrial membrane potential, and Western blotting for mitochondrial fusion- and mitochondrial autophagy-related proteins. Results: Apigenin exerts antioxidant effects by activating the Nrf2 pathway, and apigenin up-regulates the expression of melanin synthesis-related proteins Tyr, TRP1, TRP2, and gp100, which are reduced in melanocytes under oxidative stress. By inhibiting the expression of senescence-related proteins p53 and p21, and delaying cellular senescence, we detected the mitochondrial membrane potential using JC-1, and found that apigenin improved the reduction in mitochondrial membrane potential in melanocytes under oxidative stress, and maintained the normal function of mitochondria. In addition, we further detected the key regulatory proteins of mitochondrial fusion and division, MFF, p-DRP1 (S637), and p-DRP1 (S616), and found that apigenin inhibited the down-regulation of fusion-associated protein, p-DRP1 (S637), and the up-regulation of division-associated proteins, MFF and p-DRP1 (S616), due to oxidative stress in melanocytes, and promoted the mitochondrial fusion and ameliorated the imbalance between mitochondrial division and fusion. We further detected the expression of fusion-related proteins OPA1 and Mitofusion-1, and found that apigenin restored the expression of the above fusion proteins under oxidative stress, which further indicated that apigenin promoted mitochondrial fusion, improved the imbalance between mitochondrial division and fusion, and delayed the loss of mitochondrial membrane potential. Apigenin promotes the expression of melanocyte autophagy-related proteins and the key mitochondrial autophagy proteins BNIP3L/Nix under oxidative stress, and activates the PINK1/Parkin signaling pathway by up-regulating the expression of autophagy-related proteins, as well as the expression of PINK1 and Parkin proteins, to promote melanocyte autophagy and mitochondrial autophagy. Conclusions: Apigenin exerts anti-melanocyte premature aging and detachment effects by promoting melanin synthesis, autophagy, and mitochondrial autophagy in melanocytes, and inhibiting oxidative cell damage and senescence.

Penicipyrrolizidinones A-C, three pyrrolizidinone alkaloids with unprecedented skeletons from the mangrove-derived fungus Penicillium sp. DM27.

Three previously undescribed pyrrolizidinone alkaloids, penicipyrrolizidinones A and B (1 and 2), possessing an unprecedented 2-methyl-2-(oct-6-enoyl)pyrrolizidin-3-one skeleton, and penicipyrrolizidinone C (3), featuring a rare 1-alkenyl-2-methyl-pyrrolizidin-3,7-dione skeleton, together with four known pyrrolidine derivatives (4-7) were isolated from the mangrove-derived fungus Penicillium sp. DM27. Their structures were elucidated through comprehensive spectroscopic analysis, theoretical calculations of ECD spectra, and the modified Mosher's method. A plausible biosynthetic pathway for penicipyrrolizidinones A-C (1-3) was proposed. Compounds 4 and 5 exhibited moderate cytotoxicity against B16-F10 melanoma cells with IC50 values of 10.5 µM and 15.5 µM, respectively.

Predictive value of a serum tumor biomarkers scoring system for clinical stage II/III rectal cancer with neoadjuvant chemoradiotherapy.

BACKGROUND: Multiple classes of molecular biomarkers have been studied as potential predictors for rectal cancer (RC) response. Carcinoembryonic antigen (CEA) is the most widely used blood-based marker of RC and has proven to be an effective predictive marker. Cancer antigen 19-9 (CA19-9) is another tumor biomarker used for RC diagnosis and postoperative monitoring, as well as monitoring of the therapeutic effect. Using a panel of tumor markers for RC outcome prediction is a practical approach. AIM: To assess the predictive effect of pre-neoadjuvant chemoradiotherapy (NCRT) CEA and CA19-9 levels on the prognosis of stage II/III RC patients. METHODS: CEA and CA19-9 levels were evaluated 1 wk before NCRT. According to the receiver operating characteristic curve analysis, the optimal cut-off point of CEA and CA19-9 levels for the prognosis were 3.55 and 19.01, respectively. The novel serum tumor biomarker (NSTB) scores were as follows: score 0: Pre-NCRT CEA < 3.55 and CA19-9 < 19.01; score 2: Pre-NCRT CEA > 3.55 and CA19-9 > 19.01; score 1: Other situations. Pathological information was recorded according to histopathological reports after the operation. RESULTS: In the univariate analysis, pre-NCRT CEA < 3.55 [P = 0.025 for overall survival (OS), P = 0.019 for disease-free survival (DFS)], pre-NCRT CA19-9 < 19.01 (P = 0.014 for OS, P = 0.009 for DFS), a lower NSTB score (0-1 vs 2, P = 0.009 for OS, P = 0.005 for DFS) could predict a better prognosis. However, in the multivariate analysis, only a lower NSTB score (0-1 vs 2; for OS, HR = 0.485, 95%CI: 0.251-0.940, P = 0.032; for DFS, HR = 0.453, 95%CI: 0.234-0.877, P = 0.019) and higher pathological grade, node and metastasis stage (0-I vs II-III; for OS, HR = 0.363, 95%CI: 0.158-0.837, P = 0.017; for DFS, HR = 0.342, 95%CI: 0.149-0.786, P = 0.012) were independent predictive factors. CONCLUSION: The combination of post-NCRT CEA and CA19-9 was a predictive factor for clinical stage II/III RC patients receiving NCRT, and the combined index had a stronger predictive effect.

[Antitumor and antimetastatic activities of plasmid pcDNA3. 1-IP10 complexed with cationic liposome in mice with 4T1 breast cancer].

OBJECTIVE: To determine the antitumor and antimetastatic effects of plasmid pcDNA3. 1-IP10 complexed with cationic liposome (DOTAP:CHOL) in mice with 4T1 breast cancer. METHODS: BALB/c mice model with 4T1 breast cancer was established. Thirty six mice with 4T1 breast cancers were divided randomly into three groups, which were intravenously injected with normal saline (200 microL), Lip-null (50 microg DNA, 200 microL) and Lip-IP10 (50 microg DNA, 200 microL) respectively every five days for six doses. The size of the tumors, the number of lung metastasis noduls and survival time were measured. Four mice from each group were sacrificed 43 days after tumor implantation. The tumor microvascula densities (MVD) were detected by immunohistochemical staining. RESULTS: Lip-IP10 inhibited the growth of tumor and the formation of lung metastasis neoplasm (P < 0.05). The Lip-IP10 group had a median of 3 lung metastasis nodules, less than the NS group (45) and Lip-null group (40) (P < 0.05). Lip-IP10 significantly prolonged the survival time of the tumor-bearing mice (P < 0.05). The histomorphometric analysis revealed a decreased MVD in the Lip-IP10 group (21.50 +/- 15.41 vs. 44.25 +/- 5.51 for the NS group and 43.45 +/- 4.21 for the Lip-null group, P < 0.05). CONCLUSION: IP10 encapsulated in cationic liposome inhibits the growths and metastases of 4T1 breast cancers, which is based on the mechanism of IP10 inhibiting tumor angiogenesis.

[Inhibition of tumour cells with hepatitis B virus x (HBx) gene adenoviral vector in vivo].

OBJECTIVE: To investigate the inhibitory effects of the hepatitis B virus x protein (HBx protein) on tumor in vivo. METHODS: H22 cells were infected with Ad-eGFP to detect infection efficiency of adenovirus. The BALB/c mouse model of malignant ascites was established by implanting H22 cell intraperitoneally into the animal, Ad-HBx, Ad-null or NS were administered intraperitoneally in BALB/c mice separately to detect HBx expression in H22 cells and effects of HBx on inhibition on proliferation of H22 cells. RESULTS: High efficiency of Ad in infecting H22 cells in vitro was observed. HBx protein was expressed in H22 cells after intraperitoneal injection of Ad-HBx. The effect of Ad-HBx on inhibition of the peritoneal capillary permeability and the ascites accumulation (P<0.05); on reduction of the number of red cells and tumor cells counted in malignant ascites (P<0.05), and on inhibition of tumor cell life cycle (the G2/M arrest) in malignant ascites were identified by flow cytometric analysis. CONCLUSION: HBx protein can be expressed in tumour cells and can inhibit the proliferation of tumour cells in vivo, and this might be a new potential treatment for malignant ascites.

A non-aggregated and tumour-associated macrophage-targeted photosensitiser for photodynamic therapy: a novel zinc(II) phthalocyanine containing octa-sulphonates.

A novel zinc(II) phthalocyanine bearing octa-sulphonates has been prepared, which is non-aggregated in water, highly photoactive and low dark-toxic. More interestingly, it exhibits specific affinity to macrophages via the scavenger receptor-A, and can selectively accumulate in tumour sites.

Effects and mechanisms of auricular vagus nerve stimulation on high-fat-diet--induced obese rats.

OBJECTIVE: Obesity is a major public health problem. Regulating food intake and promoting metabolism of fat are two important options for treating obesity. Auricular vagus nerve stimulation (AVNS) is considered as an alternative approach to vagal nerve stimulation. The aim of this study was to investigate the effects of AVNS and its mechanisms on obesity in obese rats. METHODS: Male Sprague-Dawley rats were fed either a high-fat diet (HFD) or a normal diet for 8 wk. Qualified HFD rats were randomly divided into three groups: the HFD group, the AVNS group, and the sham group for 6 wk treatment. Body weight and daily energy intake were recorded weekly. The rats were sacrificed for measurement of weight of bilateral perirenal, epididymal white adipose tissue (WAT), dorsal brown adipose tissue (BAT), and gastric emptying. Serum cholecystokinin (CCK), peptide YY3 to 36 (PYY3-36) and norepinephrine (NE) were assayed by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was used to assess the mRNA expressions of CCK subtype receptor a (CCKa) in the antrum, PYY3-36 receptor in the distal ileum, ß3-adrenoceptor, and uncoupling protein gene 1 (UCP1) in the BAT. RESULTS: Compared with HFD group, AVNS significantly reduced body weight and epididymal WAT and increased BAT weight, serum NE, mRNA expressions of ß3-adrenoceptors, and UCP1 of the BAT, but had no effect on daily energy intake, perirenal WAT weight, gastric emptying, serum levels of CCK and PYY, or mRNA expressions of CCKa receptor and PYY3-36 receptor in the relevant tissues. The sham group, as a comparison group for AVNS, saw less effect in any of the indexes compared with the HFD group. AVNS had more effect on weight loss, reduction of perirenal WAT, and increase of NE, ß3-adrenoceptor, and UCP1 than sham. CONCLUSIONS: AVNS was more effective in reducing body weight and causing visceral fat loss. Biochemical tests found more NE released in the serum and more ß3-adrenoceptor and UCP1 expression in the BAT. All of these features suggested that energy expenditure might play an important role in obesity management by AVNS.

[Effects of light quality on the growth characteristics and biochemical component of Chlorella pyrenoidosa].

Effect of light quality, including red light, blue light, white light, red and blue mixing light with ratios of 8: 1, 8:2 and 8 : 3, on the growth characteristics and biochenmical composition of Chlorella pyrenoidosa was investigated based on light emitting diode (LED). Results showed that Chlorella pyrenoidosa grew best under blue light, and the optical density, specific growth rate and biomass of Chlorella pyrenoidosa was about 2.4, 0.10 d(-1) and 0.64 g x L(-1), respectively, while the optical density of Chlorella pyrenoidosa was between 1.0 and 1.7, the specific growth rate was between 0.07-0.10 d(-1) and the biomass was between 0.27 and 0.38 g x L(-1) under other light quality after 30 days of cultivation. Under blue light, the optical density, specific growth rate and biomass of Chlorella pyrenoidosa was approximately 2.05 times, 1.33 times and 2.06 times higher than red light, respectively. Moreover, red and blue mixing light was conducive to the synthesis of chlorophyll a and ß-carotene of Chlorella pyrenoidosa, and blue light could promote the synthesis of chlorophyll b. Chlorophyll a and carotenoids content of Chlorella pyrenoidosa was 13.5 mg xg(-1) and 5.8 mg x g(-1) respectively under red and blue mixing light with a ratio of 8:1, while it was 8.4 mg x g(-1) and 3.6 mg x g(-1) respectively under blue light. Red and blue mixing light was more conducive to protein and total lipid content per dry cell of Chlorella pyrenoidosa. Protein and total lipid content was 489.3 mg x g(-1) and 311.2 mg x g(-1) under red and blue mixing light with a ratio of 8 : 3, while it was 400.9 mg x g(-1) and 231.9 mg x g(-1) respectively under blue light.

[Effect of electroacupuncture on hippocampal LTP in Alzheimer' s disease rats induced by Abeta(25-35)].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the learning-memory ability in Alzheimer's disease(AD) rats. METHODS: Thirty SD rats were equally randomized into control, model and EA groups. AD model was established by injecting beta-amyloid (Abeta(25-35), 10 microg) into the bilateral dentate gyri of the hippocampal CA 1 area (AP--3.5 mm, ML +/- 2.0 mm, DV 2.7 mm). EA (4 Hz, 1-2 mA) was applied to "Baihui" (GV 20), "Dazhui" (GV 14), bilateral "Shenshu" (BL 23) and bilateral "Yongquan" (KI 1) for 30 min, once daily for 7 days. The learning-memory ability was detected by using step-down test. Long term potentiation (LTP) of hippocampal CA 1 area was recorded by using tungsten microelectrodes after high frequency stimulation (HFS) conditioning of the cortical anterior perforated substance. RESULTS: In AD rats, the error number and total error time of step-down test were increased significantly (P < 0.05, P < 0.01), and the slope of the excitatory postsynaptic potential (EPSP), and the amplitude and area of population spikes (PS) at 30 min, 60 min, 90 min and 120 min after high-frequency stimulation of the cortical anterior perforated substance lowered markedly in comparison with sham operation (control) group (P < 0.05, P < 0.01). After EA treatment, the error number and total error time decreased significantly, the slope of EPSP, and the amplitude and area of PS from 30 min to 120 min after high-frequency stimulation increased considerably in comparison with model group (P < 0.05, P < 0.01), suggesting an improvement of the synaptic transmission after EA. CONCLUSION: EA can improve AD rats' learning-memory ability and raise the slope of EPSP and the amplitude of PS, which may contribute to its effect in relieve symptoms of AD in clinic.

Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer.

Metastatic breast cancers are hard to treat and almost always fatal. Chloroquine diphosphate, a derivative of quinine, has long been used as a potent and commonly used medicine against different human diseases. We therefore investigated the effects of chloroquine diphosphate on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 mouse breast cancer cells with chloroquine diphosphate resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated that induction of apoptosis was associated with the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase. The effect of chloroquine diphosphate was then examined using a mice model in which 4T1 cells were implanted subcutaneously. Chloroquine diphosphate (25mg/kg and 50mg/kg, respectively) significantly inhibited the growth of the implanted 4T1 tumor cells and induced apoptosis in the tumor microenvironment. Moreover, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggested that chloroquine diphosphate might have chemotherapeutic efficacy against breast cancer including inhibition of metastasis.