Self-Assembly of Peptides as an Alluring Approach toward Cancer Treatment and Imaging.

Cancer is a severe threat to humans, as it is the second leading cause of death after cardiovascular diseases and still poses the biggest challenge in the world of medicine. Due to its higher mortality rates and resistance, it requires a more focused and productive approach to provide the solution for it. Many therapies promising to deliver favorable results, such as chemotherapy and radiotherapy, have come up with more negatives than positives. Therefore, a new class of medicinal solutions and a more targeted approach is of the essence. This review highlights the alluring properties, configurations, and self-assembly of peptide molecules which benefit the traditional approach toward cancer therapy while sparing the healthy cells in the process. As targeted drug delivery systems, self-assembled peptides offer a wide spectrum of conjugation, biocompatibility, degradability-controlled responsiveness, and biomedical applications, including cancer treatment and cancer imaging.

Intrinsic Strain-Mediated Ultrathin Ceria Nanoantioxidant.

Metal oxide nanozymes have emerged as the most efficient and promising candidates to mimic antioxidant enzymes for treatment of oxidative stress-mediated pathophysiological disorders, but the current effectiveness is unsatisfactory due to insufficient catalytic performance. Here, we report for the first time an intrinsic strain-mediated ultrathin ceria nanoantioxidant. Surface strain in ceria with variable thicknesses and coordinatively unsaturated Ce sites was investigated by theoretical calculation analysis and then was validated by preparing ∼1.2 nm ultrathin nanoplates with ∼3.0% tensile strain in plane/∼10.0% tensile strain out of plane. Compared with nanocubes, surface strain in ultrathin nanoplates could enhance the covalency of the Ce-O bond, leading to increasing superoxide dismutase (SOD)-mimetic activity by ∼2.6-fold (1533 U/mg, in close proximity to that of natural SOD) and total antioxidant activity by ∼2.5-fold. As a proof of concept, intrinsic strain-mediated ultrathin ceria nanoplates could boost antioxidation for improved ischemic stroke treatment in vivo, significantly better than edaravone, a commonly used clinical drug.

Cell membrane-specific self-assembly of peptide nanomedicine induces tumor immunogenic death to enhance cancer therapy.

Immunogenic cell death (ICD), as an unusual cell death pattern, mediates cancer cells to release a series of damage-associated molecular patterns (DAMPs), and is widely used in the field of cancer immunotherapy. Injuring the cell membrane can serve as a novel ICD initiation strategy. In this study, a peptide nanomedicine (PNpC) is designed using the fragment CM11 of cecropin, which is effective in disrupting cell membranes because of its α-helical structure. PNpC self-assembles in situ in the presence of high levels of alkaline phosphatase (ALP) on the tumor cell membrane, transforming from nanoparticles to nanofibers, which reduces the cellular internalization of the nanomedicine and increases the interaction between CM11 and tumor cell membranes. Both in vitro and in vivo results indicate that PNpC plays a significant role in killing tumor cells by triggering ICD. The ICD induced by the destruction of the cancer cell membrane is accompanied by the release of DAMPs, which promotes the maturation of DCs and facilitates the presentation of tumor-associated antigens (TAA), resulting in the infiltration of CD8+ T cells. We believe that PNpC can trigger ICD while killing cancer cells, providing a new reference for cancer immunotherapy.

In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK]2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, which induces the aggregation of ALP and the protein-lipid phase separation on cell membrane. Consequently, KYp internalization is 2-fold enhanced compared to non-responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self-assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy.

Investigation and estimation of the prevalence of drug addicts in Xichang, china.

To use a new method to estimate the prevalence of drug addicts in Xichang for the first time and to suggest that Chinese Center for Disease Control and Prevention should strengthen surveillance and intervention for them.The Capture-Mark-Recapture (CMR) method of 3 correlated sources under the simple random sampling and its formulas detailed in this paper were applied to a survey of issues relevant to drug addicts in Xichang, China.To view half a year as reacquisition time, the prevalence of drug users in Xichang could be 5264 in 2014, accounting for 0.7% of the resident population of the same year.This investigation method and its formulas studied in this paper have both high reliability and high validity, being worthy of promotion in terms of estimating the prevalence of drug addicts in other parts of the world.

HIV, syphilis, and behavioral risk factors among female sex workers before and after implementation of harm reduction programs in a high drug-using area of China.

OBJECTIVE: To evaluate the impact of harm reduction programs on HIV and syphilis infection and related risk behaviors among female sex workers (FSWs) in a drug trafficking city in Southwest China. DESIGN: Before and after harm reduction program study. METHODS: Two cross-sectional surveys were conducted among FSWs before and after harm reduction programs were launched in Xichang city, Sichuan province. The first and second cross-sectional surveys were conducted in 2004 and 2010, respectively. Temporal changes in odds of HIV, syphilis, and behavioral risk factors were assessed by multivariable logistic regression while controlling for socio-demographics. RESULTS: The 2004 and 2010 cross-sectional surveys recruited 343 and 404 FSWs, respectively. From 2004 to 2010, the odds of syphilis infection decreased by 35% and was of borderline statistical significance (AOR: 0.65, 95% CI: 0.41-1.03), while odds of HIV infection rose, but not significantly (AOR: 4.12, 95% CI: 0.76-22.45). Although odds of unprotected sex with primary sex partners did not significantly change over time (AOR: 0.96; 95% CI: 0.61-1.50), odds of unprotected sex with clients declined significantly and remarkably (AOR: 0.14, 95% CI: 0.09-0.21). Notably, the odds of reporting ≥10 new sex partners in the previous month increased by 37% (AOR: 1.37; 95% CI: 0.98-1.90). CONCLUSIONS: Harm reduction strategies may be an effective means of reducing unprotected sex with clients among FSWs. Future research is needed to better target both FSWs and IDUs and interrupt bridging networks for HIV transmission in high drug-using areas of China.

Evaluation of harm reduction programs on seroincidence of HIV, hepatitis B and C, and syphilis among intravenous drug users in southwest China.

OBJECTIVE: The aim of this study was to evaluate the impact of a multifaceted harm reduction program by comparing seroincidence rates of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and syphilis before and after implementation of harm reduction strategies among intravenous drug users (IDUs) in a drug-trafficking city in Southwest China. DESIGN: This is a prospective cohort study with 24 months of follow-up. METHODS: Two prospective cohorts (cohort 2002-2004 and cohort 2006-2008) were followed up every 6 months for seroconversions of HIV, HCV, and syphilis antibodies and HBV surface antigen. RESULTS: After implementation of harm reduction strategies in Xichang city, Sichuan province, the HIV incidence rate among IDUs significantly dropped from 2.5 to 0.6 cases per 100 person-years. Subanalyses also indicated that the incidence rate of HBV significantly declined from 14.2 to 8.8 cases per 100 person-years. No significant changes in the seroincidence rates of HCV or syphilis were detected after implementation of IDU harm reduction strategies. CONCLUSIONS: Harm reduction strategies may help reduce the high incidence of certain blood-borne infectious diseases and sexual transmitted diseases among high-risk IDUs in southwest China. Additional research is needed on the implementation and evaluation of harm reduction strategies in China.

Gender and ethnic disparities of HIV and syphilis seroconversions in a 4-year cohort of injection drug users.

This study assessed gender and ethnic disparities of HIV and syphilis seroconversions in a cohort of injection drug users (IDUs) in Southwest China. A cohort of HIV-seronegative IDUs was followed up from November 2002 to January 2007. The average seroincidence for HIV and syphilis was 2.2 and 4.2 per 100 person-years (PYs), respectively. Multivariable Poisson regression models indicated that the predictors for incident HIV seroconversion included non-Han minority ethnic groups (RR: 5.2; 95% CI: 1.9-14.4) and injecting drugs > or = 7 times/week in the past 3 months (RR: 3.6; 95% CI: 1.4-9.8). The predictors for incident syphilis seroconversion included female (RR: 4.1; 95% CI: 1.8-9.3) and being married or cohabiting (RR: 2.7; 95% CI: 1.2-5.9). These findings suggested that HIV continues to spread among IDUs, especially among Yi and other minority ethnic groups, and frequent risky injections might be the major diver of the epidemic. Female IDUs are disproportionally affected by syphilis. Further research is needed to better understand the ethnicity disparity for HIV and gender disparity for syphilis.

Factors Associated with Recent Risky Drug Use and Sexual Behaviors among Drug Users in Southwestern China.

A cross-sectional survey was conducted in 2007 among 504 drug users who were recruited mainly from detoxification centers in southwest China. About one-third (34.3%) of participants reported recent risky drug use behavior, which was defined as injecting drugs in the past 3 months, and more than one-fifth (21.6%) reported recent risky sexual behavior, or had multiple sexual partners in the past 30 days. Male sex (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.2-3.2) and more episodes of detoxification (OR, 3.7; 95% CI, 2.3-6.0) were associated with higher odds of risky drug use behavior, while unmarried status (OR, 1.7; 95% CI, 1.0-2.9), higher personal annual income (OR, 1.8; 95% CI, 1.1-2.8) and history of sexually transmitted infections (OR, 3.7; 95% CI, 2.1-6.6) were associated with higher odds of having risky sexual behavior. Subgroup analyses showed 15% participants who used drugs in the past 3 months also shared needles, and 77% participants who had multiple sexual partners in the past 30 days did not use condoms during sex with non-primary sexual partners. The study findings are useful for developing HIV risk reduction intervention programs among drug users.

[Factors associated with retention in a community-based methadone maintenance treatment among heroin addicts].

OBJECTIVE: To explore factors associated with retention in a community-based methadone maintenance treatment (MMT) among heroin addicts in Xichang of Sichuan province. METHODS: All 206 heroin addicts were first admitted to MMT community-based program between March to September 2004. Baseline data of patients characteristics, social function, drug using behaviors, sexual behaviors, dose of methadone and retention were collected. RESULTS: Up to Oct, 2005, all 206 patients contributed 8.98 +/- 5.74 person-months of following-up. The retention rates were 58.7% after 6 months and 34.6% after 12 months respectively. Cox proportional hazard regression model indicated that the employed (HR, 0.60; 95% CI, 0.39 - 0.92), helping family to do housework in past 30 days more than once a day (HR, 0.59; 95% CI, 0.42 - 0.82) and previous self-detoxification > or = 3 times (HR, 0.65; 95% CI, 0.47 - 0.91) were independently associated with retention. CONCLUSION: We should give individual counseling to help heroin addicts increasing compliance.

[A prospective cohort study on human immunodeficiency virus and syphilis seroconversion among injecting drug users].

OBJECTIVE: To study the rate of human immunodeficiency virus (HIV) seroconversion, HIV transmission and related risk factors among injecting drug users (IDUs) in an area of Sichuan province. METHODS: In November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang county of Sichuan province, China. Follow-up visits were carried out every 6 months to study the situation of drug use, sexual behaviors of the IDUs and blood specimens were collected to test for antibodies against HIV and syphilis. RESULTS: During a 24-month follow-up period, cohort retention rate and HIV incidence were 75.7% and 2.53 per 100 person-years [95% confidence interval (CI): 1.10-3.97)], respectively. Multivariate Poisson regression model showed that risk factors which were significantly associated with HIV seroconversion would include: ethnicity (RR = 12.42; 95% CI: 2.72-56.74, P = 0.0012) and needle or syringe sharing in the past 3 months (RR = 4.06; 95% CI: 1.29-12.81, P = 0.0168). Syphilis seroconversion in this cohort was 4.71 per 100 person-years (95% CI: 2.59-6.82). In multivariate Poisson regression being female (RR = 4.42; 95% CI: 1.78-10.99, P = 0.0014) appeared to be the only factor which was significantly associated with syphilis seroconversion. CONCLUSION: Our study results showed that there was a rapid transmission of HIV and syphilis among IDUs in Sichuan province, suggesting that effective intervention should be urgently taken.

Syphilis among female sex workers in southwestern China: potential for HIV transmission.

OBJECTIVE: The objective of this study was to investigate the prevalence and risk factors of syphilis infection among female sex workers in a southwestern Chinese city along a drug trafficking route. METHODS: From December 2004 to January 2005, 343 female sex workers (FSWs) were recruited through community outreach and peer referring. Confidential questionnaire interviews were administered to collect information on sexual and other sexually transmitted diseases/HIV risk behaviors. Cervical and blood samples were collected to test for syphilis and HIV antibodies and Neisseria gonorrhoeae infection; Condyloma acuminatum infection was diagnosed clinically. RESULTS: Of 343 FSWs, 15.7% were infected with syphilis. The prevalence of HIV, gonorrhea, and C. acuminatum was 0.6%, 2.0%, and 1.5%, respectively. The subtype of 2 HIV-1 infections was both CRF 07BC. Nearly 10% of FSWs reported using illicit drugs. Consistent use, inconsistent use, and never use of condoms with commercial sex clients in the last month were reported by 53.9%, 38.5%, and 7.6% FSWs, respectively. Longer duration of sex work (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.08-3.62), working at low-end establishments (OR = 2.03; 95% CI = 1.10-3.76), and if primary sex partners had sex with other women in the past 6 months (OR = 2.06; 95% CI = 1.08-3.91) were independently associated with syphilis infection. CONCLUSIONS: High prevalence of syphilis and overlapped unprotected commercial sex and drug using behaviors among FSWs along a drug-trafficking route may suggest a potential for rapid spread of HIV from injection drug users to FSWs and then to the general population and underscore the urgency of preventive interventions to break the bridge of FSWs for HIV/sexually transmitted disease spread.