Socioeconomics, health-related factors, and tooth loss among the population aged over 80 years in China.

BACKGROUND: The prevalence of tooth loss varies across the globe among oldest-old individuals. The presence of fewer than 20 teeth in old age was associated with a decrease in people's health and quality of life. This paper explored the association between socioeconomics, health-related factors, and tooth loss among the population over the age of 80 in China. METHODS: The tooth loss status of older Chinese adults was collected with a structured questionnaire from the 8th wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 6716 individuals aged 80 years and above were included. Logistic regression was used to assess the association between socioeconomic statuses, dietary intake at approximately 60 years old, health-related factors, and tooth loss. RESULTS: Of the 6716 individuals aged 80 years and above, the composition of the group with fewer teeth for both men and women was statistically significant in many ways. Multivariate logistic regression analyses show that for men, being older than 90 years and being ADL disabled (adjusted OR: 1.71, 95% CI: 1.01-2.89) are factors that are significantly and consistently associated with a higher risk of having fewer than 20 teeth, while having a higher household income per capita (adjusted OR: 0.56, 95% CI: 0.32-0.99) decreases the risk. For women, an age of above 95 years, brushing teeth less than once per day (adjusted OR: 1.96, 95% CI: 1.26-3.03), consuming sugar some of the time as opposed to less than once per month at approximately 60 years old (adjusted OR = 1.74, 95% CI: 1.15-2.62), and being ADL disabled (adjusted OR: 1.70, 95% CI: 1.04-2.77) are factors that are significantly associated with the risk of having fewer than 20 teeth. CONCLUSION: The analysis suggests that socioeconomic status, dietary intake in early old age, and ADL capacity are associated with the risk of having fewer teeth for the population aged 80 years and above, and the risk factors vary between sexes.

Engineered Polymer Nanoplatforms for Targeted Tumor Cells and Controlled Release Cargos to Enhance Cancer Treatment.

Cancer is composed of a series of uncontrollable cells, which finally form tumors to negatively impact the functions of the body and induce other serious diseases, even leading to death. During the last decades, scientists have devoted great efforts to study cancer; however, there are no effective diagnoses and treatments. Nanomaterials have attracted great attention in the biomedical field in recent years, which are widely used as optical imaging probes and delivery systems for cancer therapy. Among the numerous nanomaterials, polymeric nanoparticles occupy a prominent position because of their tunable micro-size, multifunctional surface, prominent biocompatibility and high drug-carrying capacity. These significant advantages of polymeric nanomaterials have significance over the traditional nanomaterials and have become a potential therapy for cancer. In this review, we focus on the applications of polymeric nanoparticles in cancer theranostics, especially as the drug delivery systems for cancer treatment. This review provides an overview on the advancement of synthesis, application of polymeric nanoparticles- based drug delivery systems and highlights the evaluation for cancer therapy.

Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro, the largest amount of tumor site accumulation and the best antitumor effect in vivo, compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.

Mitochondria-targeting nanomedicine: An effective and potent strategy against aminoglycosides-induced ototoxicity.

We report a proof-of-concept for the development of mitochondria-targeting nanoparticles (NPs) loaded with geranylgeranylacetone (GGA) to protect against a wide range of gentamicin-induced ototoxicity symptoms in a zebrafish model. The polymeric NPs were functionalized with a mitochondrial-homing peptide (d­Arg­Dmt­Orn­Phe­NH2) and exhibited greater mitochondrial uptake and lower gentamicin uptake in hair cells via mechanotransduction (MET) channels and tuned machinery in the hair bundle than the ordinary NPs did. Blockade of MET channels rapidly reversed this effect, indicating the reversible responses of hair cells to the targeting NPs were mediated by MET channels. Pretreatment of hair cells with mitochondria-targeting GGA-loaded NPs exhibited a superior acute or chronic protective efficacy against subsequent exposure to gentamicin compared with unmodified formulations. Mitochondrial delivery regulating the death pathway of hair cells appeared to cause the therapeutic failure of untargeted NPs. Thus, peptide-directed mitochondria-targeting NPs may represent a novel therapeutic strategy for mitochondrial dysfunction-linked diseases.

Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB0,+ for efficient tumor therapy.

As the demand for nutrients in malignant proliferation of tumors increases, the L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) of tumor cells are more highly expressed than normal cells which can be used as new targets for active targeting of cancer. However, drug delivery systems often require multi-target design to achieve simultaneous targeting of different receptors or transporters due to the heterogeneity of the tumor. Here we utilized triethylamine-sucrose octasulfate gradient to actively encapsulate irinotecan into the introliposomal aqueous phase. Targeted ability was achieved through inserting different amino acids modified polyethylene glycol monostearate into the liposomes, and found that glutamate-liposomes can be targeted to LAT1, lysine-liposomes can be targeted to ATB0,+, and inspiringly, tyrosine-liposomes can be simultaneously targeted to LAT1 and ATB0,+. The tyrosine-modified liposomes showed the highest cellular uptake in BxPC-3 and MCF-7 cells which were highly expressed both LAT1 and ATB0,+. Moreover, we validated their targeting capabilities and elucidated the transport mechanism of LAT1 and ATB0,+-mediated endocytosis. The tumor inhibition rate of tyrosine-modified liposomes greatly increased from 39% to 87% compared with commercially available liposomes loaded CPT-11(Onivyde®). Overall, it showed a good application prospect for efficient tumor therapy and industrial production.

Mitochondria-homing peptide functionalized nanoparticles performing dual extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity.

One of the major challenges in the treatment of hearing loss is the low efficacy of therapeutic candidates. To achieve the optimum drug efficacy, we designed a novel peptide (D-Arg-Dmt-Arg-Phe-NH2)-mediated mitochondrial targeted delivery nanosystem for a promising candidate, geranylgeranylacetone (GGA). The zebrafish lateral line system, a robust model for mammalian hair cells, was used to identify the efficacy against gentamicin, a well-known ototoxic agent. The nanosystem facilitated lysosomal escape and mitochondrial accumulation, and thus conferred superior protective efficacy against a wide range of gentamicin compared with unmodified NPs and free drugs. Meanwhile, peptides-modified NPs internalized hair cells via both of dynamin-dependent and independent routes, following a classic endocytic or autophagy pathway. Although extracellular action via MET channels, the primary protective mechanism underlying peptides-modified NPs was revealed due to their intracellular interaction. Thus, our nanoplatform provided a general strategy to enhance the clinical efficacy of a broad range of drugs in the treatment of hearing loss.

Novel SS-31 modified liposomes for improved protective efficacy of minocycline against drug-induced hearing loss.

Hearing loss, which is regarded as a worldwide public health concern, lacks approved therapeutic strategies. Current drug candidates used to treat hearing loss commonly have low efficacy. To achieve the optimum drug efficacy, we designed a liposome system to preload a clinically approved, water-soluble drug, minocycline. Inspired by our previous research, we used a mitochondria-targeting tetrapeptide, SS-31, to modify the surface of liposomes. The results revealed that SS-31 modified, minocycline-loaded liposomes significantly increased hair cell survival against chronic exposure to gentamicin in a zebrafish model. The designed formulation maintained the activity of mechanotransduction channels in the hair cells, and thus did not result in any alteration in gentamicin uptake. This suggested that the protective efficacy of the liposomes was induced by modulating targets associated with cell death. Further studies are required to clarify the exact intracellular mechanism of the designed formulation and to determine its clinical benefits in patients with hearing dysfunction.

SS-31 peptide enables mitochondrial targeting drug delivery: a promising therapeutic alteration to prevent hair cell damage from aminoglycosides.

Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method. The zebrafish lateral line sensory system was used as an in vivo evaluating platform to investigate the protective efficiency against gentamicin. SS-31 modification significantly reduced the activity of mechanoelectrical transduction (MET) channel and gentamicin uptake in zebrafish lateral line hair cells. As expected, SS-31 conjugated nanoparticles showed mitochondrial specific accumulation in hair cells when compared with unconjugated formulations. Furthermore, intracellular SS-31 modified PLGA NPs slightly enhanced mitochondrial membrane potential (MMP, ΔΨm) and then returned to a steady-state, indicating their effect on the respiratory chain complexes in mitochondria. GGA loaded SS-31 conjugated nanoparticles demonstrated the most favorable hair cells survivals against gentamicin when compared with unconjugated groups whereas blank formulations failed to exhibit potency, indicating that the efficiency was attributed to drug delivery of GGA. These results suggest that our constructed mitochondria-targeting PLGA based DDS have potential application in protecting hair cells from ototoxic agents.