Short, Medium and Long-Term Cause-Specific Mortality Following First-Ever Heart Failure Hospitalisation in New Zealand.

BACKGROUND: Heart failure (HF) is associated with high mortality, but there are limited reports on the underlying cause of death. This study reports short-, medium- and long-term cause-specific mortality following first-ever HF hospitalisation in New Zealand. METHOD: First-ever HF hospitalisations were identified from hospital discharge coding between 2010 and 2013. Mortality outcomes were obtained via anonymised linkage to national datasets. Short (0-30 days), medium (31-364 days), and long-term (1-5 years) mortality rates were identified. Cause of death was identified from death certification coding and classified as cardiovascular and non-cardiovascular. Cox regression analysis was performed to adjust for confounding variables. RESULTS: A cohort of 34,264 individuals with first-ever HF hospitalisation were identified. Mean age was 75.8±13 years and 50.5% were male. A total of 21,637 (63.1%) died within 5 years of hospitalisation; 4,122 (12.0%) within the first 30 days, 6,358 (18.6%) between 31-364 days, and 11,157 (32.6%) between 1 and 5 years. Older age, male gender, Maori ethnicity, higher socioeconomic deprivation and increased comorbidity were independent factors associated with higher all-cause mortality. Cardiovascular causes accounted for 51% of total deaths. Cardiovascular mortality was 6.0%, 9.5%, and 16.7% at 30 days, 31-364 days, and 1-5 years, respectively. The most common causes of non-cardiovascular mortality were neoplasms, chronic respiratory diseases and infections, accounting for 14.6%, 11.0%, and 5.5% of total deaths respectively. Comorbidity was associated with higher non-cardiovascular mortality (hazard ratio [HR] 3.35; 95% confidence interval [CI] 3.16-3.55) but not cardiovascular mortality (HR 0.79; 95% CI 0.72-0.86). CONCLUSIONS: In New Zealand, mortality following first-ever HF hospitalisation is high. Non-cardiovascular death is common and there are ethnic inequities.

Pillar Pain After Minimally Invasive and Standard Open Carpal Tunnel Release: A Systematic Review and Meta-analysis.

Purpose: Pillar pain is a recognized postoperative complication of carpal tunnel release (CTR). Minimally invasive and alternative surgical techniques can theoretically prevent pillar pain, and the aim of this review was to compare the incidence of pillar pain after standard open CTR and alternative surgical techniques. Methods: MEDLINE, Embase, and Scopus databases were thoroughly searched. Randomized controlled trials comparing minimally invasive surgical techniques to standard open CTR were identified. Data, including surgical technique, number of hands, incidence of pillar pain, and follow-up intervals, were extracted. Odds ratios (OR) were expressed as pillar pain incidence in the intervention group relative to standard open CTR. Results: There were 12 studies included. No statistically significant differences were noted among endoscopic (OR = 0.53, P = .20), flexor retinaculum lengthening (OR = 1.00, P = 1.00), short incision (OR = 0.41, P = .07) or illuminated knife techniques (OR = 0.18, P = .16). There was a statistically significant decrease in pillar pain after minimally invasive CTR (OR = 0.41, 95% confidence interval 0.20-0.86, I2 = 0%, P = .02) between 3- and 6-months follow-up; however, analyses at all other follow-up periods failed to reach statistical significance. Conclusions: Although our findings suggest that standard open CTR may be associated with an increased duration of pillar pain between 3 and 6 months postoperatively, our results suggest that minimally invasive CTR techniques do not affect either the initial development or persistence of pillar pain. Clinical relevance: Our results illustrate the natural history of pillar pain with the majority of cases resolving after 6 months, highlighting the utility of symptomatic and conservative treatments and patient education in the management of pillar pain.

Synergistic interaction between pay-it-forward incentives and recreational drug use on hepatitis B virus and hepatitis C virus testing among men who have sex with men in China.

OBJECTIVES: Pay-it-forward incentives effectively promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men (MSM) by offering free testing and donation opportunities. This study aims to explore the interaction between pay-it-forward incentives and recreational drug use on HBV and HCV testing uptake among Chinese MSM. METHODS: We pooled data from two pay-it-forward studies that aimed to promote dual HBV and HCV testing among MSM in Jiangsu, China. We explored factors associated with hepatitis testing uptake in the two study groups and examined the interaction between pay-it-forward incentives and recreational drug use on hepatitis testing uptake. RESULTS: Overall, 511 MSM participated in these two studies, with 265 participants in the pay-it-forward incentives group and 246 participants in the standard-of-care group. Among these participants, 59.3% in the pay-it-forward incentive group and 24.8% in the standard-of-care group received dual HBV and HCV testing, respectively. In the pay-it-forward incentives group, participants who used recreational drugs in the past 12 months (adjusted OR (AOR)=1.83, 95% CI 1.09 to 3.06) were more likely to receive dual HBV and HCV testing, compared with those who never used recreational drugs, whereas in the standard-of-care group, those who used recreational drugs were less likely to receive dual HBC and HCV testing (AOR=0.38, 95% CI 0.18 to 0.78). MSM with higher community connectedness (AOR=1.10, 95% CI 1.00 to 1.21) were also more likely to receive hepatitis testing with pay-it-forward incentives. There was a synergistic interaction on both the multiplicative (ratio of ORs=4.83, 95% CI 1.98 to 11.7) and additive scales (the relative excess risk of interaction=2.97, 95% CI 0.56 to 5.38) of pay-it-forward incentives and recreational drug use behaviours on dual HBV and HCV testing uptake among MSM. CONCLUSION: Pay-it-forward incentives may be particularly useful in promoting hepatitis testing among MSM who use recreational drugs.

Cellular strategies to induce immune tolerance after liver transplantation: Clinical perspectives.

Liver transplantation (LT) has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management. However, long-term side-effects of immunosuppressants, like infection, metabolic disorders and malignant tumor are gaining more attention. Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants, but the liver function and intrahepatic histology maintain normal. The approaches to achieve immune tolerance after transplantation include spontaneous, operational and induced tolerance. The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up. No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation. With the understanding to the underlying mechanisms of immune tolerance, many strategies have been developed to induce tolerance in LT recipients. Cellular strategy is one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells. The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials, while obstacles still exist before translating into clinical practice. Here, we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

Ginkgetin effectively mitigates collagen and AA-induced platelet activation via PLCγ2 but not cyclic nucleotide-dependent pathway in human.

Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5-1 µM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P-selectin expression, intracellular calcium ([Ca2+ ]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß and mitogen-activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator-stimulated phosphoproteinSer157 or Ser239 . Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2-PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.

CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer.

Colorectal cancer (CRC) ranks among the most prevalent forms of cancer globally, and its late-stage survival outcomes are less than optimal. A more nuanced understanding of the underlying mechanisms behind CRC's development is crucial for enhancing patient survival rates. Existing research suggests that the expression of Cell Wall Biogenesis 43 C-Terminal Homolog (CWH43) is reduced in CRC. However, the specific role that CWH43 plays in cancer progression remains ambiguous. Our research seeks to elucidate the influence of CWH43 on CRC's biological behavior and to shed light on its potential as a therapeutic target in CRC management. Utilizing publicly available databases, we examined the expression levels of CWH43 in CRC tissue samples and their adjacent non-cancerous tissues. Our findings indicated lower levels of both mRNA and protein expressions of CWH43 in cancerous tissues. Moreover, we found that a decrease in CWH43 expression correlates with poorer prognoses for CRC patients. In vitro experiments demonstrated that the suppression of CWH43 led to increased cell proliferation, migration, and invasiveness, while its overexpression had inhibitory effects. Further evidence from xenograft models showed enhanced tumor growth upon CWH43 silencing. Leveraging data from The Cancer Genome Atlas (TCGA), our Gene Set Enrichment Analysis (GSEA) indicated a positive relationship between low CWH43 expression and the activation of the epithelial-mesenchymal Transition (EMT) pathway. We conducted RNA sequencing to analyze gene expression changes under both silenced and overexpressed CWH43 conditions. By identifying core genes and executing KEGG pathway analysis, we discovered that CWH43 appears to have regulatory influence over the TTK-mediated cell cycle. Importantly, inhibition of TTK counteracted the tumor-promoting effects caused by CWH43 downregulation. Our findings propose that the decreased expression of CWH43 amplifies TTK-mediated cell cycle activities, thus encouraging tumor growth. This newly identified mechanism offers promising avenues for targeted CRC treatment strategies.

HPV Infection Profiles among People Living with HIV and HPV Vaccine Acceptance among Individuals with Different HIV Infection Statuses in China: A Systematic Meta-Analysis.

To understand the HPV infection profiles among Chinese HIV/AIDS patients and the HPV vaccine acceptance among unvaccinated Chinese people with different HIV infection statuses after the HPV vaccine launch in China, this study searched Web of Science, PubMed, Cochrane Library, Embase, Scopus, CNKI, WANFANG, SinoMed, and VIP databases up to 23 June 2023, according to the registered protocol (CRD42023449913). A total of 58 studies were included. The results showed that the HPV infection rate among Chinese HIV/AIDS patients was 52.54% (95% CI: 42.11-62.86%) and higher in males than in females (74.55% vs. 41.04%); meanwhile, the rate was higher in the anus than in the cervix (69.22% vs. 41.71%). Although there was no statistical difference, the high-risk HPV infection rate (38.98%) was higher than low-risk HPV (23.86%), and single infections were more common (28.84%) than multiple infections (19.23%). HPV vaccine acceptance among the unvaccinated Chinese population was 59.19% (95% CI: 52.50-65.89%), and was slightly higher among HIV-infected rather than non-HIV-infected individuals (67.72% vs. 59.58%). There was a difference in acceptance among respondents from different regions. Although the difference in acceptance rate between males and females was not statistically significant (61.10% vs. 61.18%), MSM had a higher acceptance rate than non-MSM (84.28% vs. 59.05%). HPV infection is prevalent among HIV patients, demonstrating the need to increase the frequency of HPV screening for PLWH. The HPV vaccine acceptance rate is higher than that of non-HIV-infected individuals. Male acceptance is almost the same as female's, with MSM acceptance higher than non-MSM, suggesting that using MSM, especially MSM in PLWH, as an entry point may be a practical avenue to explore to further expand the scope of HPV vaccination.

Li+ mobility powered by a crystal compound for fast Li-S chemistry.

Placing blocking layers between electrodes has shown paramount prospects in suppressing the shuttle effect of Li-S batteries, but the associated ionic transport would be a concurrent obstacle. Herein, we present a Li-based crystal composited with carbon (LiPN2@C) by a one-step annealing of Li+ absorbed melamine polyphosphate, which simultaneously achieves alleviated polysulfide-shuttling and facilitated Li+ transport. As a homologous crystal, LiPN2 with abundant lithiophilic sites makes Li+ transport more efficient and sustainable. With a LiPN2@C-modified separator, the Li2S cathode exhibits a much-lower activation potential of 2.4 V and a high-rate capacity of 519 mA h g-1 at 2C. Impressively, the battery delivers a capacity of 726 mA h g-1 at 0.5C with a low decay rate of 0.25% per cycle during 100 continuous cycles.

Modulation of cancer-associated fibroblasts by nanodelivery system to enhance efficacy of tumor therapy.

Cancer-associated fibroblasts (CAFs) are the most common cells in the tumor stroma and are essential for tumor development and metastasis. While decreasing the release and infiltration of nanomedicine through nonspecific internalization, CAFs specifically increase solid tumor pressure and interstitial fluid pressure by secreting tumor growth- and migration-promoting cytokines, which increases vascular and organ pressure caused by solid tumor pressure. Nanoparticles have good permeability and can penetrate tumor tissue to reach the lesion area, inhibiting tumor growth. Thus, CAFs are used as modifiable targets. Here, the authors review the biological functions, origins and biomarkers of CAFs and summarize strategies for modulating CAFs in nanodelivery systems. This study provides a prospective guide to modulating CAFs to enhance oncology treatment.

Cancer-associated fibroblasts (CAFs) participate in the growth and metastasis of cancer and also suppress the penetration of antitumor drugs into the deep tumor tissue. Therefore, many researchers have sought to improve the therapeutic efficacy of nanomedicine through the regulation of CAFs. Some nanoparticles that can precisely target CAFs can slow their growth while also assisting the immune system in fighting cancer cells and releasing pressure within the tumor. These nanoparticles may pass through tumors and inhibit the growth of cancer cells. Therefore, the modulation of CAFs with nanomedicines to enhance tumor therapy is essential.

Fast-Charging Sodium-Ion Batteries Enabled by Molecular-Level Designed Nitrogen and Phosphorus Codoped Mesoporous Soft Carbon.

Soft carbons have attracted extensive interests as competitive anodes for fast-charging sodium-ion batteries (SIBs); however, the high-rate performance is still restricted by their large ion migration barriers and sluggish reaction kinetics. Herein, we show a molecular design approach toward the fabrication of nitrogen and phosphorus codoped mesoporous soft carbon (NPSC). The key to this strategy lies in the chemical cross-linking reaction between polyphosphoric acid and p-phenylenediamine, associated with pyrolysis induced in-situ self-activation that creates mesoporous structures and rich heteroatoms within the carbon matrix. Thanks to the enlarged interlayer spacing, reduced ion diffusion length, and plentiful active sites, the obtained NPSC delivers a superb rate capacity of 215 mAh g-1 at 10 A g-1 and an ultralong cycle life of 4,700 cycles at 5 A g-1. Remarkably, the full cell shows 99% capacity retention during 100 continuous cycles, and maximum energy and power densities of 191 Wh kg-1 and 9.2 kW kg-1, respectively. We believe that such a synthetic protocol could pave a novel venue to develop soft carbons with unique properties for advanced SIBs.

In silico analysis to identify miR-1271-5p/PLCB4 (phospholipase C Beta 4) axis mediated oxaliplatin resistance in metastatic colorectal cancer.

Oxaliplatin (OXA) is the first-line chemotherapy drug for metastatic colorectal cancer (mCRC), and the emergence of drug resistance is a major clinical challenge. Although there have been numerous studies on OXA resistance, but its underlying molecular mechanisms are still unclear. This study aims to identify key regulatory genes and pathways associated with OXA resistance. The Gene Expression Omnibus (GEO) GSE42387 dataset containing gene expression profiles of parental and OXA-resistant LoVo cells was applied to explore potential targets. GEO2R, STRING, CytoNCA (a plug-in of Cytoscape), and DAVID were used to analyze differentially expressed genes (DEGs), protein-protein interactions (PPIs), hub genes in PPIs, and gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. R2 online platform was used to run a survival analysis of validated hub genes enriched in KEGG pathways. The ENCORI database predicted microRNAs for candidate genes. A survival analysis of those genes was performed, and validated using the OncoLnc database. In addition, the 'clusterProfiler' package in R was used to perform gene set enrichment analysis (GSEA). We identified 395 DEGs, among which 155 were upregulated and 240 were downregulated. In total, 95 DEGs were screened as hub genes after constructing the PPI networks. Twelve GO terms and three KEGG pathways (steroid hormone biosynthesis, malaria, and pathways in cancer) were identified as being significant in the enrichment analysis of hub genes. Twenty-one hub genes enriched in KEGG pathways were defined as key genes. Among them AKT3, phospholipase C Beta 4 (PLCB4), and TGFB1 were identified as OXA-resistance genes through the survival analysis. High expressions of AKT3 and TGFB1 were each associated with a poor prognosis, and lower expression of PLCB4 was correlated with worse survival. Further, high levels of hsa-miR-1271-5p, which potentially targets PLCB4, were associated with poor overall survival in patients with CRC. Finally, we found that PLCB4 low expression was associated with MAPK signaling pathway and VEGF signaling pathway in CRC. Our results demonstrated that hsa-miR-1271-5p/PLCB4 in the pathway in cancer could be a new potential therapeutic target for mCRC with OXA resistance.

A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases.

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02557490.

CRISPR-mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line.

Squamous and anaplastic thyroid cancers are the most aggressive and life-threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is < 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti-cancer therapies to suppress VEGF/VEGFR-mediated cancer development in patients with clinical advanced thyroid cancer.

Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities.

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), are characterized by the progressive degeneration of neurons. Although the etiology and pathogenesis of neurodegenerative diseases have been studied intensively, the mechanism is still in its infancy. In general, most neurodegenerative diseases share common molecular mechanisms, and multiple risks interact and promote the pathologic process of neurogenerative diseases. At present, most of the approved drugs only alleviate the clinical symptoms but fail to cure neurodegenerative diseases. Numerous studies indicate that dietary plant polyphenols are safe and exhibit potent neuroprotective effects in various neurodegenerative diseases. However, low bioavailability is the biggest obstacle for polyphenol that largely limits its adoption from evidence into clinical practice. In this review, we summarized the widely recognized mechanisms associated with neurodegenerative diseases, such as misfolded proteins, mitochondrial dysfunction, oxidative damage, and neuroinflammatory responses. In addition, we summarized the research advances about the neuroprotective effect of the most widely reported dietary plant polyphenols. Moreover, we discussed the current clinical study and application of polyphenols and the factors that result in low bioavailability, such as poor stability and low permeability across the blood-brain barrier (BBB). In the future, the improvement of absorption and stability, modification of structure and formulation, and the combination therapy will provide more opportunities from the laboratory into the clinic for polyphenols. Lastly, we hope that the present review will encourage further researches on natural dietary polyphenols in the treatment of neurodegenerative diseases.

Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Photoreactive Cytosine-Functionalized Self-Assembled Micelles with Enhanced Cellular Uptake Capability for Efficient Cancer Chemotherapy.

Design, fabrication, and control of photoreactive supramolecular macromers─which are composed of a thermoresponsive polymer backbone and photoreactive nucleobase end-groups─to achieve the desired physical-chemical performance and provide the high efficiency required for chemotherapy drug delivery purposes still present challenges. Herein, a difunctional cytosine-terminated supramolecular macromer was successfully obtained at high yield. UV-irradiation induces the formation of cytosine photodimers within the structure. The irradiated macromer can self-assemble into nanosized spherical micelles in water that possess a number of interesting and unique features, such as desired micellar size and morphology, tunable drug-loading capacity, and excellent structural stability in serum-containing medium, in addition to well-controlled drug-release behaviors in response to changes in environmental temperature and pH; these extremely desirable, rare features are required to augment the functions of polymeric nanocarriers for drug delivery. Importantly, a series of in vitro studies demonstrated that photodimerized cytosine moieties within the drug-loaded micelles substantially enhance their internalization and accumulation inside cells via endocytosis and subsequently lead to induction of massive apoptotic cell death compared with the corresponding nonirradiated micelles. Thus, this newly developed "photomodified" nanocarrier system could provide a potentially fruitful route to enhance the drug delivery performance of nanocages without the need to introduce targeting moieties or additional components.

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment.

This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

MicroRNA-373-3p inhibits the growth of cervical cancer by targeting AKT1 both in vitro and in vivo.

OBJECTIVE: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. METHODS: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. RESULTS: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. CONCLUSION: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.

Evaluation of Urine NDRG1 as Noninvasive Biomarker for Bladder Cancer Diagnosis.

BACKGROUND: N-myc downstream regulated gene 1 (NDRG1) was involved in cell differentiation and was recently reported to exert various effects in tumorigenesis. The aim of this study was to assess its diagnostic value in urine as a useful marker for bladder cancer (BC). METHODS: In this study, we recruited 119 BC patients, 65 patients with non-cancerous bladder diseases, and 60 healthy volunteers as control. Their urine concentrations of NDRG1, nuclear matrix protein 22 (NMP22), and creatinine (Cr) were measured and relevant clinical information was retrieved from their medical history records. RESULTS: The expression of NDRG1/Cr and NMP22/Cr in urine were significantly higher in BC patients than those in non-cancerous bladder diseases (p = 0.009 and p = 0.023) and healthy controls (p = 0.005 and p = 0.002). The level of NDRG1/Cr was significantly associated with pathologic T stage (p < 0.001) and pathological grade (p < 0.001). The ROC of NDRG1/Cr to diagnose BC was 0.713 (95% CI, 0.630 - 0.797), with a sensitivity of 63.8% and a specificity of 73.4% at a cutoff of 76.3 ng/mg. NMP22/Cr was 0.705 (95% CI, 0.626 - 0.784), with a sensitivity of 64.2% and a specificity of 66.2% at a cutoff of 12.1 ng/mg. NDRG1/Cr in combination with NMP22/Cr shows a ROC of 0.719 (95% CI, 0.632 0.806) with a sensitivity of 64.9% and specificity of 75.9% Conclusions: Urine NDRG1 may be useful in a minimally invasive modality for determining bladder cancer. Predictive value of the two biomarkers was slightly higher than that of routine NMP22 parameter alone.