Comparison of two different intravitreal treatment regimens combined with systemic antiviral therapy for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR). METHODS: A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections. RESULTS: In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05). CONCLUSIONS: The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones.

Exploring the potential anti-Alzheimer disease mechanisms of Alpiniae Oxyphyliae Fructus by network pharmacology study and molecular docking.

Alpiniae Oxyphyliae Fructus (AOF) (yizhi) is a frequently medicated Chinese herb for Alzheimer disease (AD) treatment. The present study investigated the components and potential mechanisms of AOF through network pharmacology analysis and molecular docking. The results showed that AOF contains at least 20 active ingredients and involves 184 target genes. A total of 301 AD-related genes were obtained from the DisGeNET, GeneCards, GEO, OMIM, and Alzheimer Disease: Genes databases. A total of 41 key targets were identified from the topology analysis of the AOF-AD target network. These key targets are involved in 105 signal pathways, such as the PI3K-Akt, HIF-1, and MAPK pathways, and can regulate gene transcription, cell death, cell proliferation, drug response, and protein phosphorylation. AOF's active ingredients, Chrysin, Isocyperol, Izalpinin, Linolenic acid, CHEMBL489541, Oxyphyllenone A, Oxyphyllenone B, and Oxyphyllol C, show high affinity to targets, including PPARG, ESR1, and AKT1. These findings provide a new basis for AOF application and anti-AD study.

Pyroptosis-related prognosis model, immunocyte infiltration characterization, and competing endogenous RNA network of glioblastoma.

BACKGROUND: Glioblastoma (GBM) has a high incidence rate, invasive growth, and easy recurrence, and the current therapeutic effect is less than satisfying. Pyroptosis plays an important role in morbidity and progress of GBM. Meanwhile, the tumor microenvironment (TME) is involved in the progress and treatment tolerance of GBM. In the present study, we analyzed prognosis model, immunocyte infiltration characterization, and competing endogenous RNA (ceRNA) network of GBM on the basis of pyroptosis-related genes (PRGs). METHODS: The transcriptome and clinical data of 155 patients with GBM and 120 normal subjects were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Lasso (Least absolute shrinkage and selection operator) Cox expression analysis was used in predicting prognostic markers, and its predictive ability was tested using a nomogram. A prognostic risk score formula was constructed, and CIBERSORT, ssGSEA algorithm, Tumor IMmune Estimation Resource (TIMER), and TISIDB database were used in evaluating the immunocyte infiltration characterization and tumor immune response of differential risk samples. A ceRNA network was constructed with Starbase, mirtarbase, and lncbase, and the mechanism of this regulatory axis was explored using Gene Set Enrichment Analysis (GSEA). RESULTS: Five PRGs (CASP3, NLRP2, TP63, GZMB, and CASP9) were identified as the independent prognostic biomarkers of GBM. Prognostic risk score formula analysis showed that the low-risk group had obvious survival advantage compared with the high-risk group, and significant differences in immunocyte infiltration and immune related function score were found. In addition, a ceRNA network of messenger RNA (CASP3, TP63)-microRNA (hsa-miR-519c-5p)-long noncoding RNA (GABPB1-AS1) was established. GSEA analysis showed that the regulatory axis played a considerable role in the extracellular matrix (ECM) and immune inflammatory response. CONCLUSIONS: Pyroptosis and TME-related independent prognostic markers were screened in this study, and a prognosis risk score formula was established for the first time according to the prognosis PRGs. TME immunocyte infiltration characterization and immune response were assessed using ssGSEA, CIBERSORT algorithm, TIMER, and TISIDB database. Besides a ceRNA network was built up. This study not only laid foundations for further exploring pyroptosis and TME in improving prognosis of GBM, but also provided a new idea for more effective guidance on clinical immunotherapy to patients and developing new immunotherapeutic drugs.

Acteoside and ursolic acid synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling: from network pharmacology to experimental validation.

CONTEXT: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. OBJECTIVE: Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism. MATERIALS AND METHODS: UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 µM), ATS (40 µM), UA (5 µM) + ATS (40 µM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. RESULTS: The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 µM) + ATS (ED50: 40 µM) could protect H2O2-induced (IC50: 250 µM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. CONCLUSIONS: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.

Ursolic acid potentiated oxaliplatin to induce apoptosis in colorectal cancer RKO cells.

Ursolic acid (UA) is found in multiple anticancer herbs and has shown anticancer effects in colorectal cancer (CRC) cells. The present study aimed to observe the effects of a combination of UA and oxaliplatin (Oxa), a frequently used chemotherapeutic drug in CRC, on human CRC RKO cells. The results showed that UA and Oxa synergistically inhibited the proliferation of RKO cells. A combination of UA and Oxa induced apoptosis in RKO cells and increased the activities of caspase-3, caspase-8, and caspase-9. Z-VAD-FMK, a caspase inhibitor, significantly antagonized UA- and Oxa-activated caspase-3, caspase-8, and caspase-9 and induced apoptosis. In addition, UA and Oxa downregulated the expression of X-linked inhibitor of apoptosis (XIAP) and Survivin in RKO cells. These observations suggested that a combination of UA and Oxa elicited synergistically anticancer effects in RKO cells and provided new evidence for potential application of UA and Oxa for CRC treatment.

Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-ß1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a vital process in cancer progression and metastasis. Yanggan Jiedu Sanjie (YGJDSJ) is Traditional Chinese Medicine formulation for liver cancer treatment. In the present study, we evaluated the effects of YGJDSJ on TGF-ß1-induced EMT in hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were treated with TGF-ß1 and YGJDSJ. EMT was identified by morphological changes and expression of marker proteins. Cell morphology was observed under a microscope. Protein expression and phosphorylation was detected by western blotting. Cell migration was measured by the scratch assay. Cell adhesion and invasion was detected by a commercial kit. RESULTS: YGJDSJ reversed TGF-ß1-induced morphological changes, as well as the expression of the EMT markers E-cadherin and N-cadherin in Bel-7402 cells. YGJDSJ also inhibited TGF-ß1 up-regulated Smad3 phosphorylation and Snail expression in Bel-7402 cells. Moreover, YGJDSJ inhibited TGF-ß1-induced cell adhesion, migration and invasion in Bel-7402 cells. CONCLUSIONS: YGJDSJ inhibited TGF-ß1-induced EMT and mediated metastatic potential of Bel-7402 cells, which may be related to down-regulation of Smad3 phosphorylation and Snail expression. The present study provides a new basis for application of this herbal formula for prevention of liver cancer metastasis.

Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis in hepatocellular carcinoma Bel-7402 cells.

BACKGROUND: Based on clinical medications and related studies, we established a Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment. In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension-grown human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and treated with YGJDSJ. Anchorage-independent cell growth was detected by cell Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis. Caspases activities were detected by the cleavage of chromogenic substrate. Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402 cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8 and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated YGJDSJ induced anoikis. CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS generation and PTK2 downregulation.

Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma.

Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.

Secondary metabolites of plants from the genus chloranthus: chemistry and biological activities.

Chloranthus, a genus of the family Chloranthaceae, which is mainly distributed in eastern and southern Asia, has been used in Chinese folk medicine due to its antitumor, antifungal, and anti-inflammatory activities. This review compiles the research on isolation, structure elucidation, structural diversity, and bioactivities of Chloranthus secondary metabolites reported between 2007 and 2013. The metabolites listed encompass 82 sesquiterpenoids, 50 dimeric sesquiterpenoids, 15 diterpenoids, one coumarin, and five other compounds. Among them, dimeric sesquiterpenoids, the characteristic components of plants from the genus Chloranthus, have attracted considerable attention due to their complex structures and significant biological features, e.g., antitumor, antibacterial, antifungal, anti-inflammatory, and hepatoprotective activities, and potent and selective inhibition of the delayed rectifier (IK) K(+) current and tyrosinase.

Acorus tatarinowii Schott extract protects PC12 cells from amyloid-beta induced neurotoxicity.

Amyloid-beta induced neurotoxicity has been identified as a major cause of Alzheimer's disease. Acorus tatarinowii Schott is one of the most frequently used Chinese herbs for Alzheimer's disease treatment. However, the effects of Acorus tatarinowii Schott on amyloid-beta mediated nerve cell damage remains unknown. In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of A. tatarinowii Schott extract (ATSE) against Abeta25-35 induced neurotoxicity. The results showed pretreatment with ATSE significantly protected PC12 cells from Abeta25-35 induced cell death, lactate dehydrogenase release, DNA damage, mitochondrial dysfunction and cytochrome c release from mitochondria. In addition, pretreatment with ATSE also significantly inhibited Abeta25-35 induced caspase-3 activation and reactive oxygen species generation in PC12 cells. These observations suggested that ATSE protects PC12 cells from amyloid-beta induced neurotoxicity.

A new method to analysis synthetic acetic acid to vinegar: Hydrogen isotope ratio at the methyl site of acetic acid in vinegar by GC-IRMS.

Acetic acid is the key organic substance used to verify the authenticity of vinegar. A new method for precisely determining acetic acid δDCH3 in vinegar via gas chromatography -pyrolytic-stable isotope ratio mass spectrometry (GC-P-IRMS) was established. The δDCH3 values were obtained via calibration with a series of standards. The optimised method demonstrated a repeatability standard deviation within 3 ‰. The standard deviation of accuracy of the new method compared with that of the SNIF-NMR method was within 2.6 ‰. The synthetic acetic acid δDCH3 values was -136.7 ‰ ± 29.6 ‰, and the δDCH3 value of acetic acid in vinegar was -414.9 ‰ ± 40.5 ‰, with significant isotopic distribution characteristics. This methodology serves as a supplementary method for measuring the δDCH3 value of acetic acid in vinegar. It has advantages over other methods in terms of time, sensitivity and operability. And provides a new idea for solving the problem of analyzing substances in the presence of exchangeable groups.

Correlation Between Prefrontal Functional Connectivity and the Degree of Cognitive Impairment in Alzheimer's Disease: A Functional Near-Infrared Spectroscopy Study.

Background: The development of Alzheimer's disease (AD) can be divided into subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Early recognition of pre-AD stages may slow the progression of dementia. Objective: This study aimed to explore functional connectivity (FC) changes of the brain prefrontal cortex (PFC) in AD continuum using functional near-infrared spectroscopy (fNIRS), and to analyze its correlation with cognitive function. Methods: All participants underwent 48-channel fNIRS at resting-state. Based on Brodmann partitioning, the PFC was divided into eight subregions. The NIRSIT Analysis Tool (v3.7.5) was used to analyze mean ΔHbO2 and FC. Spearman correlation analysis was used to examine associations between FC and cognitive function. Results: Compared with HC group, the mean ΔHbO2 and FC were different between multiple subregions in the AD continuum. Both mean ΔHbO2 in the left dorsolateral PFC and average FC decreased sequentially from SCD to MCI to AD groups. Additionally, seven pairs of subregions differed in FC among the three groups: the differences between the MCI and SCD groups were in heterotopic connectivity; the differences between the AD and SCD groups were in left intrahemispheric and homotopic connectivity; whereas the MCI and AD groups differed only in homotopic connectivity. Spearman correlation results showed that FCs were positively correlated with cognitive function. Conclusions: These results suggest that the left dorsolateral PFC may be the key cortical impairment in AD. Furthermore, there are different resting-state prefrontal network patterns in AD continuum, and the degree of cognitive impairment is positively correlated with reduced FC strength.

Teng-Long-Bu-Zhong-Tang, a Chinese herbal formula, enhances anticancer effects of 5--Fluorouracil in CT26 colon carcinoma.

BACKGROUND: Colorectal cancer remains one of the leading causes of cancer death worldwide. Traditional Chinese Medicine (TCM) has played a positive role in colorectal cancer treatment. There is a great need to establish effective herbal formula for colorectal cancer treatment. Based on TCM principles and clinical practices, we have established an eight herbs composed formula for colorectal cancer treatment, which is Teng-Long-Bu-Zhong-Tang (TLBZT). We have demonstrated the anticancer effects of TLBZT against colorectal carcinoma in vitro. In present study, we evaluated the anticancer potential of TLBZT, used alone or in combination with low dose of 5-Fluorouracil (5-Fu), in CT26 colon carcinoma in vivo. METHODS: CT26 colon carcinoma was established in BALB/c mice and treated with TLBZT, 5-Fu, or TLBZT plus 5-Fu. The tumor volumes were observed. Apoptosis was detected by TUNEL assay. Caspases activities were detected by colorimetric assay. Cell senescence was indentified by senescence ß-galactosidase staining. Gene expression and angiogenesis was observed by immunohistochemistry or western blot. RESULTS: TLBZT significantly inhibited CT26 colon carcinoma growth. TLBZT elicited apoptosis in CT26 colon carcinoma, accompanied by Caspase-3, 8, and 9 activation and PARP cleavage, and downregulation of XIAP and Survivin. TLBZT also induced cell senescence in CT26 colon carcinoma, with concomitant upregulation of p16 and p21 and downregulation of RB phosphorylation. In addition, angiogenesis and VEGF expression in CT26 colon carcinoma was significantly inhibited by TLBZT treatment. Furthermore, TLBZT significantly enhanced anticancer effects of 5-Fu in CT26 colon carcinoma. CONCLUSIONS: TLBZT exhibited significantly anticancer effect, and enhanced the effects of 5-Fu in CT26 colon carcinoma, which may correlate with induction of apoptosis and cell senescence, and angiogenesis inhibition. The present study provides new insight into TCM approaches for colon cancer treatment that are worth of further study.

Sodium valproate induces cell senescence in human hepatocarcinoma cells.

Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP), a known HDAC inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP treatment caused a large and flat morphology change, positive SA-ß-gal staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low dose SVP treatment also increased acetylation of histone H3 and H4 on p21 promoter, accompanied by up-regulation of p21 and down-regulation of RB phosphorylation. These observations suggested that a low dose of SVP could induce cell senescence in hepatocarcinoma cells, which might correlate with hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB phosphorylation. Since the effective concentration inducing cell senescence in hepatocarcinoma cells is clinically available, whether a clinical dose of SVP could induce cell senescence in clinical hepatocarcinoma is worthy of further study.

[Effect of Solanum nigrum on human colon carcinoma RKO cells ].

OBJECTIVE: To evaluate the effect of Solanum nigrum on adhesion, migration and invasion in human colon carcinoma RKO cells. METHODS: RKO cells were treated with different dose of Solanum nigrum. Cell proliferation was detected by CCK-8 assay. Cell adhesion was observed with CytoSelect 48-Well Cell Adhesion Assay. Cell migration was detected with scratch assay. Cell invasion was analyzed by CytoSelect 24-Well Cell Invasion Assay. RESULTS: At final concentration of 400-1600 microg/mL, Solanum nigrum significantly inhibited proliferation of RKO cells in a dose-dependent manner. At final concentration of 100-400 microg/mL, Solanum nigrum significantly inhibited adhesion,migration and invasion in RKO cells. CONCLUSION: Solanum nigrum may inhibit the proliferation, adhesion, migration and invasive abilities in RKO cells. The present study provides new insight into the application of Solanum nigrum for colon carcinoma treatment that are worthy of further study.

Polygonum cuspidatum Extract Induces Anoikis in Hepatocarcinoma Cells Associated with Generation of Reactive Oxygen Species and Downregulation of Focal Adhesion Kinase.

Anoikis has been recognized as a potential target for anticancer therapy. Polygonum cuspidatum (Huzhang) is a frequently used Chinese herb in hepatocarcinoma. In present study, we evaluated the effects of Polygonum cuspidatum extract (PCE) in hepatocarcinoma cells in suspension. The results showed that PCE inhibited the proliferation of hepatocarcinoma cells in suspension in a dose- and time-dependent manner. PCE also inhibited anchorage-independent growth of hepatocarcinoma cells in soft agar. PCE induced anoikis in human hepatocarcinoma Bel-7402 cells accompanied by caspase-3 and caspase-9 activation and poly(ADP-ribose) polymerase cleavage, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. In addition, PCE treatment induced intracellular reactive oxygen species (ROS) production in Bel-7402 cells. NAC, an ROS scavenger, partially attenuated PCE-induced anoikis and activation of caspase-3 and caspase-9. Furthermore, PCE inhibited expression of focal adhesion kinase (FAK) in Bel-7402 cells. Overexpression of FAK partially abrogated PCE-induced anoikis. These data suggest that PCE may inhibit suspension growth and induce caspase-mediated anoikis in hepatocarcinoma cells and may relate to ROS generation and FAK downregulation. The present study provides new insight into the application of Chinese herb for hepatocarcinoma treatment.

Signal pathways in the treatment of Alzheimer's disease with traditional Chinese medicine.

AIM OF THE REVIEW: This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), and provide support for further investigation on TCM and its active ingredients. MATERIALS AND METHODS: Literature survey was conducted using PubMed, Web of Science, Google Scholar, CNKI, and other databases, with "Alzheimer's disease," "traditional Chinese medicine," "medicinal herb," "Chinese herb," and "natural plant" as the primary keywords. RESULTS: TCM could modulate signal pathways related to AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, and PI3K/Akt/mTOR, as well as SIRT1 and PPARα pathway. It could regulate crosstalk between pathways through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating ubiquitin-proteasome system function, modulating autophagy, and eventually improving cognitive impairment in patients with AD. CONCLUSION: TCM could be multilevel, multitargeted, and multifaceted to prevent and treat AD. In-depth research on the prevention and treatment of AD with TCM could provide new ideas for exploring the pathogenesis of AD and developing new anti-AD drugs.

Comparison of intravitreal ranibizumab monotherapy vs. ranibizumab combined with dexamethasone implant for macular edema secondary to retinal vein occlusion.

Purpose: To compare the efficacy and the injection number of intravitreal ranibizumab (IVR) monotherapy vs. intravitreal ranibizumab plus dexamethasone (IVR + DEX) implants for macular edema (ME) secondary to retinal vein occlusion (RVO). Methods: This prospective, control trial comprised 96 eyes of 96 patients with ME due to non-ischemic RVO divided into two groups. The IVR monotherapy group consisted of 61 patients (29 with CRVO and 32 with BRVO) treated with ranibizumab with three consecutive loading doses at a monthly + pro re nata (three + PRN) regimen. The IVR + DEX implant group consisted of 35 patients (19 with CRVO and 16 with BRVO) treated with intravitreal ranibizumab plus DEX implant. All eyes underwent best-corrected visual acuity (BCVA, log MAR), central foveal thickness (CFT), and intraocular pressure (IOP). In case of recurrence, each group received initial medication. Results: At the 12-month visit, the mean log MAR BCVA that was improved from baseline was 0.23 with the IVR group and 0.30 with the IVR + DEX group. CFT decreased on average by 420 ± 292 µm with the IVR group and 393 ± 259 µm with the IVR + DEX implant group. No significant differences were detected in BCVA improvement and CFT reduction between the two groups (p > 0.05). The mean number of injections was 5.4 in the IVR group and 3.9 in the IVR + DEX implant group (p < 0.001). The mean reinjection interval for patients with the IVR + DEX implant was 131.2 ± 8.9 days (range: 98-150). The incidence of high IOP and cataract progression were significantly higher in the IVR + DEX implant group than in the IVR group (both p < 0.001). Conclusion: In RVO-ME, the IVR + DEX implant did not have synergistic efficacy, providing further improvement in BCVA and a reduction in CFT. However, the IVR + DEX implant still had an advantage in reducing the number of injections and prolonging the time between injections.

Lycopene Alleviates Titanium Dioxide Nanoparticle-Induced Testicular Toxicity by Inhibiting Oxidative Stress and Apoptosis in Mice.

PURPOSE: The research was carried out to investigate the possible ameliorative effect of lycopene on TiO2 NPs-induced male reproductive toxicity and explore the possible mechanism. METHODS: Ninety-six healthy male Institute of Cancer Research (ICR) mice were equally divided into eight groups (control group, 50 mg/kg TiO2 NPs group, 5 mg/kg LYC group, 20 mg/kg LYC group, 40 mg/kg LYC group, 50 mg/kg TiO2 NPs + 5 mg/kg LYC group, 50 mg/kg TiO2 NPs + 20 mg/kg LYC group, 50 mg/kg TiO2 NPs + 40 mg/kg LYC group), and the mice were treated by intragastric administration every day for 30 days in this research. Sperm parameters, testicular histopathology, oxidant and antioxidant enzymes, and cell apoptosis-related protein expression in the testicular tissue were analyzed. RESULTS: The results showed that TiO2 NPs exposure significantly decreased sperm count and motility, and TiO2 NPs also increased sperm malformation in the epididymis; these characteristics were improved when co-administration with LYC. Testicular histopathological lesions like disorder of germ cells arrange, detachment, atrophy, and vacuolization were observed after TiO2 NPs exposure, and these abnormalities were effectively ameliorated by co-administration with LYC. Oxidative stress was induced by TiO2 NPs exposure as evidenced by increased the level of MDA and decreased the activity of SOD as well as the level of anti-O2-, and these alterations were effectively prevented by co-administration with LYC. LYC also alleviated TiO2 NPs-induced germ cell apoptosis by inhibiting mitochondrial apoptotic pathway, as shown by the upregulation of Bcl-2, the downregulation of Bax, Cleaved Caspase 3, and Cleaved Caspase 9. CONCLUSION: LYC could ameliorate TiO2 NPs-induced testicular damage via inhibiting oxidative stress and apoptosis, which could be used to alleviate the testicular toxicity associated with TiO2 NPs intake.

miR-92a-3p Promoted EMT via Targeting LATS1 in Cervical Cancer Stem Cells.

miR-92a-3p (microRNA-92a-3p) has been reported to be dysregulated in several cancers, and as such, it is considered to be a cancer-related microRNA. However, the influence of miR-92a-3p on biological behaviors in cervical cancer (CC) still remains unclear. Quantitative real-time PCR was used to detect miR-92a-3p levels in CC stem cells. Here, Cell Counting Kit-8 (CCK8) assay, Transwell cell invasion assay and flow cytometry assay were used to characterize the effects that miR-92a-3p and large tumor suppressor l (LATS1) had on proliferation, invasion and cell cycle transition. The luciferase reporter gene assay was used to verify the targeting relationship between miR-92a-3p and LATS1. Western Blotting was used to investigate the related signaling pathways and proteins. Data from The Cancer Genome Atlas (TCGA) showed that miR-92a-3p was upregulated in CC tissues and closely associated with overall survival. miR-92a-3p promoted proliferation, invasion and cell cycle transition in CC stem cells. The luciferase reporter assay showed that miR-92a-3p bound to the 3'-untranslated region (3'-UTR) of the LATS1 promoter. LATS1 inhibited proliferation, invasion and cell cycle transition. Results measured by Western Blotting showed that LATS1 downregulated expressions of transcriptional co-activator with PDZ-binding motif (TAZ), vimentin and cyclin E, but upregulated the expression of E-cadherin. Re-expression of LATS1 partly reversed the effects of miR-92a-3p on proliferation, invasion and cell cycle transition, as well as on TAZ, E-cadherin, vimentin, and cyclin E. miR-92a-3p promoted the malignant behavior of CC stem cells by targeting LATS1, which regulated TAZ and E-cadherin.