Smart glypican-3-targeting peptide-chlorin e6 conjugates for targeted photodynamic therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal malignancy with poor prognosis, necessitating the urgent development of effective treatments. Targeted photodynamic therapy (PDT) offers a promising way to selectively eradicate tumor cells without affecting normal cells. Inspired by promising features of peptide-drug conjugates (PDCs) in targeted cancer therapy, herein a novel glypican-3 (GPC3)-targeting PDC-PDT strategy was developed for the precise PDT treatment of HCC. The GPC3-targeting photosensitizer conjugates were developed by attaching GPC3-targeting peptides to chlorin e6. Conjugate 8b demonstrated the ability to penetrate HCC cells via GPC3-mediated entry process, exhibiting remarkable tumor-targeting capacity, superior antitumor efficacy, and minimal toxicity towards normal cells. Notably, conjugate 8b achieved complete tumor elimination upon light illumination in a HepG2 xenograft model without harm to normal tissues. Overall, this innovative GPC3-targeting conjugation strategy demonstrates considerable promise for clinical applications for the treatment of HCC.

The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study.

BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.

Cadmium-Free Kesterite Thin-Film Solar Cells with High Efficiency Approaching 12.

Cadmium sulfide (CdS) buffer layer is commonly used in Kesterite Cu2 ZnSn(S,Se)4 (CZTSSe) thin film solar cells. However, the toxicity of Cadmium (Cd) and perilous waste, which is generated during the deposition process (chemical bath deposition), and the narrow bandgap (≈2.4 eV) of CdS restrict its large-scale future application. Herein, the atomic layer deposition (ALD) method is proposed to deposit zinc-tin-oxide (ZTO) as a buffer layer in Ag-doped CZTSSe solar cells. It is found that the ZTO buffer layer improves the band alignment at the Ag-CZTSSe/ZTO heterojunction interface. The smaller contact potential difference of the ZTO facilitates the extraction of charge carriers and promotes carrier transport. The better p-n junction quality helps to improve the open-circuit voltage (VOC ) and fill factor (FF). Meanwhile, the wider bandgap of ZTO assists to transfer more photons to the CZTSSe absorber, and more photocarriers are generated thus improving short-circuit current density (Jsc). Ultimately, Ag-CZTSSe/ZTO device with 10 nm thick ZTO layer and 5:1 (Zn:Sn) ratio, Sn/(Sn + Zn): 0.28 deliver a superior power conversion efficiency (PCE) of 11.8%. As far as it is known that 11.8% is the highest efficiency among Cd-free kesterite thin film solar cells.

Energy Band Alignment by Solution-Processed Aluminum Doping Strategy toward Record Efficiency in Pulsed Laser-Deposited Kesterite Thin-Film Solar Cell.

Kesterite-based Cu2ZnSnS4 (CZTS) thin-film photovoltaics involve a serious interfacial dilemma, leading to severe recombination of carriers and insufficient band alignment at the CZTS/CdS heterojunction. Herein, an interface modification scheme by aluminum doping is introduced for CZTS/CdS via a spin coating method combined with heat treatment. The thermal annealing of the kesterite/CdS junction drives the migration of doped Al from CdS to the absorber, achieving an effective ion substitution and interface passivation. This condition greatly reduces interface recombination and improves device fill factor and current density. The JSC and FF of the champion device increased from 18.01 to 22.33 mA cm-2 and 60.24 to 64.06%, respectively, owing to the optimized band alignment and remarkably enhanced charge carrier generation, separation, and transport. Consequently, a photoelectric conversion efficiency (PCE) of 8.65% was achieved, representing the highest efficiency in CZTS thin-film solar cells fabricated by pulsed laser deposition (PLD) to date. This work proposed a facile strategy for interfacial engineering treatment, opening a valuable avenue to overcome the efficiency bottleneck of CZTS thin-film solar cells.

Intracranial delivery of synthetic mRNA to suppress glioblastoma.

Owing to messenger RNA's unique biological advantages, it has received increasing attention to be used as a therapeutic, known as mRNA-based gene therapy. It is critical to have an ideal strategy of mRNA gene therapy for glioma, which grows in a special environment. In the present study, we screened out a safe and efficient transfection reagent for intracranial delivery of synthetic mRNA in mouse brain. First, in order to analyze the effect of different transfection reagents on the intracranial delivery of mRNA, the synthetic luciferase mRNA was wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Then, to test the therapeutic effect of our intracranial delivery mRNA model on glioma, synthetic modified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was used as an example of therapeutic application. This model demonstrated that synthetic mRNA could be successfully delivered into the brain using commercially available transfection reagents, and TransIT-mRNA showed better results than in vivo-jetPEI kit. This model can be applied in precise targeting and personalized gene therapy of glioma.

Circ-METTL15 contributes to the proliferation, metastasis, immune escape and restrains apoptosis in lung cancer by regulating miR-1299/PDL1 axis.

BACKGROUND: Circular RNAs (circRNAs) are important regulators in the pathogenesis of lung cancer. The study aims to explore the function and mechanism of circRNA methyltransferase-like 15 (circ-METTL15) in lung cancer development. METHODS: The expression of circ-METTL15, miR-1299 and programmed death-ligand 1 (PDL1) were investigated by qRT-PCR assay. Cell viability, colony formation, cell proliferation and invasion were determined by MTT, colony formation, EDU incorporation and transwell assays, respectively. Cell apoptosis was attested by flow cytometry and TUNEL assays. Interferon-γ (IFN-γ) and Tumour Necrosis Factor-α (TNF-α) production were tested by enzyme-linked immunosorbent assay (ELISA), and the survival rate of cancer cells was assessed by cytotoxicity analysis. The protein expression was examined by western blot or immunohistochemistry (IHC) assay. The interaction between miR-1299 and circ-METTL15 or PDL1 was confirmed via dual-luciferase reporter assay. Xenograft models were established in mice to explore the role of circ-METTL15 in tumour growth in vivo. RESULTS: Circ-METTL15 was upregulated in lung cancer tissues and cells. Circ-METTL15 silencing suppressed cell proliferation, colony formation, invasion, immune escape and promoted cell apoptosis in lung cancer cells. Circ-METTL15 was a sponge of miR-1299, and it could exert regulatory function in lung cancer via miR-1299. Furthermore, PDL1 was a functional target of miR-1299, and miR-1299 inhibited lung cancer cell development via decreasing PDL1 expression. Moreover, circ-METTL15 controlled PDL1 expression by acting as a sponge of miR-1299. Besides, circ-METTL15 downregulation blocked lung cancer tumour growth in vivo by regulating the miR-1299/PDL1 axis. CONCLUSION: Circ-METTL15 promoted lung cancer malignant progression at least partly through modulating PDL1 by sponging miR-1299.

Stabilizing Interface between Li2S-P2S5 Glass-Ceramic Electrolyte and Ether Electrolyte by Tuning Solvation Reaction.

Using solid-liquid hybrid electrolytes is an effective strategy to overcome the large solid/solid interfacial resistance in all-solid-state batteries and the safety problems in liquid batteries. The properties of the solid/liquid electrolyte interphase layer (SLEI) are essential for the performance of solid-liquid hybrid electrolytes. In this work, the solvation reactions between Li2S-P2S5 glass-ceramic solid electrolytes (SEs) and ether electrolytes were studied, and their influence on the SLEI was examined. Although 1,2-dimethoxyethane (DME) reacted with the Li2S-P2S5 glass-ceramic SE to form a dense SLEI, 1,3-dioxolane (DOL) severely corroded the SE, resulting in a loose SLEI. Consequently, a stable SLEI formed with DME. Using a combination of the Li2S-P2S5 glass-ceramic SE and the DME-based liquid electrolyte (LE), stable lithium plating/stripping cycles over 1000 h and a hybrid Li-S battery that retained a specific capacity of 730 mAh g-1 after 200 cycles were demonstrated. The knowledge of the reactions between the sulfide electrolytes and the organic LEs is instructive for the design of stable sulfide-liquid hybrid electrolytes for advanced batteries.

HOXD9­induced SCNN1A upregulation promotes pancreatic cancer cell proliferation, migration and predicts prognosis by regulating epithelial­mesenchymal transformation.

Pancreatic cancer (PC) is a malignant tumor disease, whose molecular mechanism is not fully understood. Sodium channel epithelial 1α subunit (SCNN1A) serves an important role in tumor progression. The current study explored the role of homeobox D9 (HOXD9) and SCNN1A in the progression of PC. The expression of SCNN1A and HOXD9 in PC samples was predicted on online databases and detected in PC cell lines. The association between SCNN1A expression and PC prognosis was examined by the Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas and Genotype­Tissue Expression databases and by a Kaplan­Meier plotter. Subsequently, the biological effects of SCNN1A on PC cell growth, colony formation, migration and invasion were investigated through RNA interference and cell transfection. Next, the expression of E­cadherin, N­cadherin, Vimentin and Snail was detected by western blotting to discover whether HOXD9 dysregulation mediated PC metastasis. Binding sites of HOXD9 and SCNN1A promoters were predicted on JASPAR. Reverse transcription­quantitative PCR and western blotting were used to detect the expression level of SCNN1A following interference and overexpression of HOXD9. Luciferase assay detected luciferase activity following interference with HOXD9 and the transcriptional activity of SCNN1A following binding site deletion. High expression of SCNN1A and HOXD9 in PC was predicted by online databases, signifying poor prognosis. The present study confirmed the above predictions in PC cell lines. Knockdown of SCNN1A and HOXD9 could effectively inhibit the proliferation, migration, invasion and epithelial­mesenchymal transition of PC cells. Furthermore, HOXD9 activated SCNN1A transcription, forming a feedback regulatory loop. HOXD9 was demonstrated to activate SCNN1A and promote the malignant biological process of PC.

Dietary Bioactive Peptide Alanyl-Glutamine Attenuates Dextran Sodium Sulfate-Induced Colitis by Modulating Gut Microbiota.

Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di-peptide alanyl-glutamine (Ala-Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala-Gln and glutamine (Gln) on dextran sulfate sodium- (DSS-) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala-Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin- (IL-) 1ß, IL-6, tumor necrosis factor-α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala-Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala-Gln or Gln. Interestingly, Ala-Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS-induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala-Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala-Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala-Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.

Wip1 controls the translocation of the chromosomal passenger complex to the central spindle for faithful mitotic exit.

Dramatic cellular reorganization in mitosis critically depends on the timely and temporal phosphorylation of a broad range of proteins, which is mediated by the activation of the mitotic kinases and repression of counteracting phosphatases. The mitosis-to-interphase transition, which is termed mitotic exit, involves the removal of mitotic phosphorylation by protein phosphatases. Although protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) drive this reversal in animal cells, the phosphatase network associated with ordered bulk dephosphorylation in mitotic exit is not fully understood. Here, we describe a new mitotic phosphatase relay in which Wip1/PPM1D phosphatase activity is essential for chromosomal passenger complex (CPC) translocation to the anaphase central spindle after release from the chromosome via PP1-mediated dephosphorylation of histone H3T3. Depletion of endogenous Wip1 and overexpression of the phosphatase-dead mutant disturbed CPC translocation to the central spindle, leading to failure of cytokinesis. While Wip1 was degraded in early mitosis, its levels recovered in anaphase and the protein functioned as a Cdk1-counteracting phosphatase at the anaphase central spindle and midbody. Mechanistically, Wip1 dephosphorylated Thr-59 in inner centromere protein (INCENP), which, subsequently bound to MKLP2 and recruited other components to the central spindle. Furthermore, Wip1 overexpression is associated with the overall survival rate of patients with breast cancer, suggesting that Wip1 not only functions as a weak oncogene in the DNA damage network but also as a tumor suppressor in mitotic exit. Altogether, our findings reveal that sequential dephosphorylation of mitotic phosphatases provides spatiotemporal regulation of mitotic exit to prevent tumor initiation and progression.

Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival.

BACKGROUND: To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. METHODS: From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast-enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. RESULTS: The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. CONCLUSION: The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.

Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells.

Oxidative damages have adverse effects on mammals. Growing studies have focused on exploring new antioxidants. Here, we report that Lactobacillus frumenti increases the total antioxidation capacity activities and decreases the total reactive oxygen species levels in porcine intestinal epithelial cells. Comparative proteomics revealed that expressions of peroxiredoxin 2, isocitrate dehydrogenase 1, NAD(P)H dehydrogenase quinone 1, antioxidant protein 1, and metallothionein-2A, which are associated with antioxidant defense system, were significantly increased with L. frumenti treatment. In germ-free mice, L. frumenti treatment also remarkably improves the intestinal antioxidant capacity. We further illustrated that nitric oxide production-mediated by nitric oxide synthase 1 activation is essential for L. frumenti-induced improvements in intestinal epithelial antioxidant capacity and barrier function. This study suggested that L. frumenti may be a potential probiotic used to prevent oxidative stress-induced aging and diseases in mammals.-Nie, Y., Hu, J., Hou, Q., Zheng, W., Zhang, X., Yang, T., Ma, L., Yan, X. Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells.

miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma.

Malignant gliomas are treated with temozolomide (TMZ) at present, but often exhibit resistance to this agent. Cancer-initiating cells (CICs) have been suggested to lead to TMZ resistance. The mechanisms underlying CICs-based TMZ resistance are not fully understood. MicroRNAs (miRNAs) have been demonstrated to serve important roles in tumorigenesis and TMZ resistance. In the present study, a sphere forming assay and western blot analysis were performed to detect the formation of CICs and fibroblast activation protein α (FAP-α) protein expression. It was revealed that TMZ resistance promoted the formation of CICs and upregulated FAP-α expression in glioblastoma cells. Over-expressing FAP-α was also demonstrated to promote TMZ resistance and induce the formation of CICs in U251MG cells. In addition, using a reverse transcription-quantitative polymerase chain reaction, it was observed that miR-204 was downregulated in U251MG-resistant (-R) cells. miR-204 expression negatively correlated with the FAP-α levels in human glioblastoma tissues, and it may inhibit the formation of CICs and reverse TMZ resistance in U251MG-R cells. Therefore, it was concluded that miR-204 reversed temozolomide resistance and inhibited CICs phenotypes by degrading FAP-α in glioblastoma.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Use of Pneumoperitoneal Puncture for Peritoneal Catheter Placement in Lumboperitoneal Shunt Surgery: Technical Note.

BACKGROUND: In hydrocephalus shunt surgery, a peritoneal catheter is traditionally inserted with laparotomy incision. The abdominal incision length will not be shorter than 3 cm in most cases. A longer incision has to be made in obese patients. The lateral position in lumboperitoneal shunt (LPS) surgery also increases the difficulty of laparotomy. This report introduces a simple technique of pneumoperitoneal puncture for peritoneal catheter placement in LPS surgery. METHODS: Twenty-eight communicating hydrocephalus cases underwent pneumoperitoneal puncture in an LPS operation. Abdominal incision length, time for peritoneal catheter placement, and postoperative complications were recorded. RESULTS: The length of the abdominal incision was 1 cm, and the average time for peritoneal catheter placement was 3.5 minutes. No patient suffered from infection and obstruction. Two cases of subdural hematoma because of cerebrospinal fluid overdrainage occurred. CONCLUSIONS: The pneumoperitoneal puncture technique has proven, in our experience, to be a minimally invasive, simple, and reliable method in a peritoneal catheter placement procedure. This technique, which needs to be assessed further by larger case series, may be considered a new method of choice for peritoneal catheter placement in LPS surgery.

Synthesis of 2-morpholinetetraphenylporphyrins and their photodynamic activities.

A series of 2-morpholinetetraphenylporphyrins functionalized with various substituents (Cl, Me, MeO group) at 4-phenyl position were prepared via nucleophilic substitution of 2-nitroporphyrin copper derivatives with morpholine by refluxing under a nitrogen atmosphere and then demetalization. Their basic photophysical properties, intracellular localization, cytotoxicities in vitro and in vivo were also investigated. All synthesized photosensitizers exhibited longer maxima absorption wavelengths than Hematoporphyrin monomethyl ether (HMME). They showed low dark cytotoxicity compared with that of HMME and were more phototoxic than HMME against Eca-109 cells in vitro. M3 also exhibited better photodynamic antitumor efficacy on BALB/c nude mice at a lower concentration. Therefore, M3 is a promising antitumor photosensitizer in photodynamic therapy application.

microRNA-23b suppresses epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma via targeting Pyk2.

Numerous microRNAs (miRNAs) have been shown to play important roles in various cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of the miRNAs involved in HCC progress and metastasis still remain unknown. We downloaded the normalized data of microRNA expression profiling of HCC comparing primary tumor with lung metastasis from GEO database (GSE26323), and gain a group of metastasis-related candidate miRNAs. Among the candidate miRNAs, we focused on miR-23b for further study. The association of metastasis-related miR-23b with survival was also explored. Furthermore, the effects of miR-23b on biological role in HCC were demonstrated by MTT proliferation assay, wound healing and migration assay and the EMT related markers was analyzed by Western blot. Potential target genes of miR-23b were predicted using TargetScan and PicTar and confirmed by luciferase activity assay. A rescue experiment was performed to verify whether the function of miR-23b was exerted via regulation of its target. Our results showed that miR-23b expression was significantly decreased in HCC tissues, which was more importantly, positively correlated to the intrahepatic metastasis of HCC. Meanwhile, patients with low miR-23b expression had significantly poorer prognosis. Overexpression of miR-23b could inhibit MHCC97L cell proliferation, migration, invasion and regulate the expression of MMPs and EMT-associated genes. Moreover, Pyk2, one of the crucial regulators of EMT, was identified as a direct target of miR-23b. In addition, the inhibitory effects of miR-23b overexpression on the metastasis could be restored by Pyk2 overexpression. This study revealed that miR-23b was a tumor suppressor which may regulate HCC migration and invasion by targeting Pyk2 via regulation of EMT, implicating a potential prognostic biomarker and therapeutic target for HCC treatment.

Safety and Efficacy of Flexible Ureteroscopy in Combination with Holmium Laser Lithotripsy for the Treatment of Bilateral Upper Urinary Tract Calculi.

OBJECTIVE: To retrospectively evaluate the safety and efficacy of flexible ureteroscopy (FURS) in combination with holmium laser lithotripsy for the treatment of bilateral upper urinary calculi. MATERIALS AND METHODS: The stone-free status was defined as the absence of any stones or asymptomatic status, or the presence of clinically insignificant residual fragments <4 mm, and was assessed by plain kidney, ureter, and bladder X-ray. The operative time, stone-free rates (SFRs), serum creatinine (SCr), and complications were recorded. RESULTS: During the operation, there was no bleeding, ureteral perforation, avulsion, and rupture. Postoperative hematuria was observed in 2 patients. SCr increased significantly on the first day after the procedure compared with the preoperative SCr, but after 4 weeks, the renal function significantly improved (p < 0.05). The SFR was 71.6% (63/88) on the first day after the first surgical procedure; it then increased to 86.4% (76/88) in the fourth week, and rose to 97.4% (76/78) after the second operation. CONCLUSION: The results demonstrated that FURS in combination with holmium laser lithotripsy represented a favorable less-invasive alternative with high SFR and acceptable complication rates in the treatment of bilateral upper urinary tract calculi.

Synthesis, characterization, and biological studies of diosgenyl analogs.

A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure-activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism.

Synthesis, photophysical properties and biological evaluation of ß-alkylaminoporphyrin for photodynamic therapy.

A series of ß-alkylaminoporphyrins conjugated with different amines at ß position (D1-D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4-D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy.