Search

Background: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission., Methods: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number  R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine., Results: We find that the basic reproduction number  R 0  is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity., Conclusion: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission., (© 2024. The Author(s).)

Background: The relationship between oxidative balance score (OBS) and diabetes remains poorly understood and may be gender-specific. We conducted a cross-sectional study to investigate the complex association between OBS and diabetes among US adults., Methods: Overall, 5,233 participants were included in this cross-sectional study. The exposure variable was OBS, composed of scores for 20 dietary and lifestyle factors. Multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were applied to examine the relationship between OBS and diabetes., Results: Compared to the lowest OBS quartile group (Q1), the multivariable-adjusted odds ratio (OR) (95% confidence interval (CI) for the highest OBS quartile group (Q4) was 0.602 (0.372-0.974) ( p for trend = 0.007), and for the highest lifestyle, the OBS quartile group was 0.386 (0.223-0.667) ( p for trend < 0.001). Moreover, gender effects were found between OBS and diabetes ( p for interaction = 0.044). RCS showed an inverted-U relationship between OBS and diabetes in women ( p for non-linear = 6e-04) and a linear relationship between OBS and diabetes in men., Conclusions: In summary, high OBS was negatively associated with diabetes risk in a gender-dependent manner., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could serve as a potential conflict of interest., (Copyright © 2023 Wu, Ren, Song, Gao, Pang and Zhang.)

Background: Oral tongue squamous cell carcinoma (OTSCC) is the most common malignancy of the oral cavity. Photodynamic therapy (PDT) has become a clinically promising approach for early stage OTSCC treatment. 5-Aminolaevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) and has been applied for PDT of cancer. However, the accumulated PpIX in 5-ALA-treated cancer cells will be further transformed into heme through ferrous iron insertion under ferrochelatase catalysis. Theoretically, iron chelation can enhance the intracellular accumulation of PpIX and thus promote 5-ALA-based PDT. Here, an iron chelator deferasirox (DFX) was used to investigate synergistic suppression effects of 5-ALA-based PDT and iron chelation on OTSCC., Methods: In OTSCC SCC-25 cells, the enhancing effect of DFX on 5-ALA-mediated accumulation of PpIX was firstly assessed. After laser irradiation (635 nm, 200 mW/cm 2 and 2 min), the synergistic cytotoxicity and apoptosis-inducing effect of 5-ALA and DFX were evaluated in SCC-25 cells, and the apoptosis mechanism was further investigated by monitoring the change of mitochondrial membrane potential and observing the subcellular localization of cytochrome c (Cyt c). In SCC-25 tumor-bearing mice, the synergistic suppression effects of 5-ALA-based PDT and DFX on tumor growth and tumor angiogenesis were investigated after laser irradiation on the tumor (635 nm, 150 mW/cm 2 and 10 min)., Results: In SCC-25 cells, DFX showed strong iron chelation effect and enhanced 5-ALA-mediated intracellular accumulation of PpIX by 2-3 folds. After laser irradiation (635 nm, 200 mW/cm 2 and 2 min), 5-ALA combined with DFX exhibited significant synergistic effects on cytotoxicity and cell apoptosis. In the treated cells, the damage of mitochondrial membrane and the release of Cyt c from mitochondria to cytoplasm were observed distinctly, indicating the activation of mitochondria-related signal pathway. In SCC-25 tumor-bearing mice, tumor growth and tumor angiogenesis were both notably suppressed by combination treatment of 5-ALA with laser irradiation and DFX. Meanwhile, no obvious toxic injuries were visible in histological examination of major organs in the treated mice., Conclusions: 5-ALA-based PDT combined with iron chelation synergistically inhibited the growth of OTSCC. Hence it can be seen that this combination therapy may represent a promising strategy for clinical treatment of OTSCC and other cancers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, a reactive oxygen species (ROS)-responsive nanoparticle system was designed for combining photodynamic therapy (PDT) and chemotherapy for oral tongue squamous cell carcinoma (OTSCC)-targeted treatment. A PEGlated prodrug (RPTD) of doxorubicin (DOX) via thioketal linkage and cRGD peptide modification was synthesized and then used to prepare nanoparticles for encapsulating photosensitizer hematoporphyrin (HP). Thus, the obtained HP-loaded RPTD (RPTD/HP) nanoparticles had a regular spherical shape and small size, approximately 180 nm. The RPTD/HP nanoparticles showed a remarkable PDT efficiency and successfully induced ROS generation upon laser irradiation both in vitro and in vivo. DOX exhibited significant ROS-responsive release property from RPTD/HP nanoparticles because of the rupture of the thioketal linker. In OTSCC cells, RPTD/HP nanoparticles were efficiently internalized and showed potent effects on cell growth inhibition and apoptosis induction after laser irradiation. In OTSCC tumor-bearing mice, RPTD/HP nanoparticles displayed excellent tumor-targeting ability and notably suppressed tumor growth through multiple mechanisms after local laser irradiation. Taken together, we supplied a novel therapeutic nanosystem for OTSCC treatment through combining PDT and chemotherapy.

Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities for targeting and penetrating head and neck squamous cell carcinoma. Here, we designed a simple but effective nanoparticle system for the delivery of doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and then PD nanoparticles were prepared by a modified nanoprecipitation method. After that, PD nanoparticles were surface-modified with HN-1 to form HNPD nanoparticles, which had a uniform spherical shape and a small size about 150nm. In human OSCC cells (CAL-27 and SCC-25), HNPD nanoparticles exhibited significantly higher cellular uptakes and cytotoxicities than PD nanoparticles. Furthermore, HNPD nanoparticles showed a certain degree of functional selectivity for CAL-27 and SCC-25 cells as compared to human hepatoma HepG2 cells. In SCC-25 tumor-bearing nude mice, HNPD nanoparticles showed remarkably enhanced tumor-targeting and penetrating efficiencies as compared to PD nanoparticles, and effectively inhibited the tumor growth. In conclusion, our study demonstrated for the first time that HN-1 could be used for mediating the OSCC-targeted delivery of nanoparticles., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To prepare a new dental topical anesthetics, lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome (LID-TAT-N), and to evaluate its transdermal properties and topical anesthesia effects., Methods: LID-TAT-N was prepared using reverse-phase evaporation method, and lidocaine loaded conventional liposome (LID-CL) was prepared in the same manner as positive control. The diameter, ζ potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured. The skin permeation of LID-TAT-N was examined, and compared with LID-CL and lidocaine injection (LID-IJ, as negative control), using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours. Each experiment was repeated six times. The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits., Results: The mean diameter of LID-TAT-N was smaller than that of LID-CL [(152.7 ± 10.6) nm vs. (259.5 ± 15.5) nm, P < 0.01]. The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group [(1 340.0 ± 97.5) µg · cm(-2)] than those of LID-CL and LID-IJ groups [(1 060.6 ± 80.2), (282.6 ± 65.1) µg · cm(-2), respectively, P < 0.05]. Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia [(24.8 ± 2.8) min] was also longer than that of LID-IJ [(14.5 ± 2.3) min, P < 0.05]., Conclusions: LID-TAT-N had good transdermal ability, and the advanced skin penetration feature can improve its tropical anesthetic effect.

Epithelial‑to‑mesenchymal transition (EMT) may result in damage to the peritoneum and the development of fibrosis in peritoneal mesothelial cells (PMCs). However, the mechanism underlying EMT in peritoneal mesothelial cells is not well understood. Heat shock proteins (HSPs) were initially identified as proteins that are expressed following exposure of cells to environmental stress. However, their function in the development of EMT in PMCs remains to be fully elucidated. In the present study, the effect of HSP70 on advanced glycation end‑products (AGEs)‑induced EMT in peritoneal mesothelial cells was investigated by overexpression of this protein using a plasmid and knockdown of HSP70 using small interfering RNA. In addition, the underlying molecular mechanisms were explored. The results demonstrated that AGEs activated changes associated with EMT, including the loss of E‑cadherin and the increase in α‑smooth muscle actin. Furthermore, AGEs also induced the upregulation of HSP70, which led to the partial inhibition of EMT in PMCs. HSP70 inhibits EMT by modulating transforming growth factor‑β (TGF‑β)/Smad expression and the mitogen‑activated protein kinases (MAPK)/extracellular signal‑regulated kinases (ERK) signaling pathways. The findings suggested that HSP70 augments the cellular defense capacity through inhibition of TGF‑β/Smad and MAPK/ERK signaling pathways, thereby protecting PMCs from AGEs‑induced EMT.

Renal tubular epithelial cells can enter the epithelial‑to‑mesenchymal transition (EMT) in response to chronic hypoxia. EMT is a process which involves the phenotypic conversion of epithelial cells, that is believed to have an important role in renal fibrosis. However, the underlying mechanisms of the involvement of EMT in renal fibrosis remain to be elucidated. Adrenomedullin (AMD) has been implicated in renal fibrosis and is induced by hypoxia. The aims of the present study were to determine whether ADM signaling was active in human proximal tubular epithelial cells cultured under hypoxic conditions, and to observe the activity of ADM during EMT. The expression levels of ADM were significantly increased, in a time‑dependent manner, in HK‑2 and HKC human proximal tubular epithelial cells, cultured under hypoxic conditions. Overexpression of exogenous ADM was accompanied by increased expression levels of the epithelial markers E‑cadherin and tight junction protein‑1, and decreased expression levels of the mesenchymal markers vimentin and α‑smooth muscle actin, during hypoxia. Knock‑down of ADM expression by small hairpin RNA, or co‑administration of an ADM peptide inhibitor, in HK‑2 cells significantly exacerbated hypoxia‑induced EMT, as compared to the lack of effect observed in the untransfected controls. ADM was shown to suppress EMT by inhibiting the activation of extracellular signal‑regulated kinase (ERK), and this effect was prevented by the ERK activator apigenin. The results of the present study suggest that ADM has an important role in promoting EMT in hypoxic human proximal tubular epithelial cells. ADM may therefore represent a novel therapeutic target in the treatment of injured kidneys.

The cyclic resistance of ProTaper Universal (size 25/08) and ProTaper Next (size 25/06) instruments was compared in artificial canals with different curvatures in this study. A total of 30 ProTaper Universal and 30 ProTaper Next instruments were divided into 6 groups (n = 10) and were operated into artificial canals with 3 different angles of curvature (45°, 60°, 90°). The canal length was kept consistent in this study. The number of cycles to fracture (NCF) was counted until file fracture occurred, at which point, the length of the fragment was measured. The data were analyzed statistically using ANOVA complemented by the Tukey test (p < 0.05). Cross sections of the fractured files were scanned by an electron microscope. In the fatigue test, the ProTaper Next displayed more resistance in 45° and 60° canals (p < 0.05), whereas ProTaper Universal exhibited a better operability in 90° canals (p < 0.05). The average length of the fragments from ProTaper Next was significantly shorter than that from ProTaper Universal in 90° canals (p < 0.05). The cross sections of the fractured surfaces became flatter when the curvature angles decreased from 90° to 45°. ProTaper Next was more reliable when shaping in curved canals, whereas ProTaper Universal was more sui for the preparation of root canals with severe curvatures.

Conventional liposomes (CLs) have been used as a transdermal drug delivery system for enhancing the delivery of hydrophilic drugs into/through the skin. However, their applications have been constrained by their limited penetration ability and poor stability. In this article, a new kind of transactivating transcriptional activator peptide (TAT)-conjugated polymeric lipid vesicles (TPLVs) formed from amphiphilic lysine-linoleic acid modified dextran (LLD) and cholesterol (Chol) has been prepared successfully. The newly developed TPLVs had a bilayer structure similar to CLs. The TPLVs also have smaller particle size, narrower distribution, higher positive charge and much better stability than the CLs; they remained stable in aqueous solutions for up to 60 days without aggregation. The in vitro and in vivo skin permeation studies revealed that TPLVs delivered a higher amount of drug through the skin than CLs, indicating enhanced drug transdermal activities. The synergetic effects of abovementioned features and the cell-penetrating peptide TAT might have contributed to the improved skin penetration ability of the TPLVs. Similar to CLs, TPLVs began to show limited cytotoxicity against human umbilical vein endothelial cells at a concentration of 200 μg mL -1 . The in vitro release profiles showed that the TPLVs achieved a sustained release of lidocaine. These results suggest that the TPLVs may be utilized as an efficient carrier to replace CLs for transdermal drug delivery.

Transactivation transcriptional activator (TAT) peptides were conjugated on the octadecyl-quaternized, lysine-modified chitosan to form polymeric liposomes (TAT-PLs) with cholesterol for improving transdermal delivery of local anesthetic lidocaine hydrochloride (LID). In this study, the LID loaded TAT-conjugated polymeric liposomes (LID-TAT-PLs) have been successfully prepared. LID-TAT-PLs were characterized by determination of their particle size, polydispersity, morphology, drug encapsulation efficiency, drug release behavior in vitro, and storage-stability. The skin permeation of LID-TAT-PLs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and penetration of TAT-PLs was visualized by confocal laser scanning microscopy (CLSM). The results showed that LID-TAT-PLs were spherical in solution, with substantially smaller mean diameter (154.7±10.7 nm), higher encapsulation efficiency (80.05±2.64%) and better stability in contrast to conventional liposomes (CLs). From the in vitro skin permeation results, transdermal flux of LID-TAT-PLs was approximately 4.17 and 1.75 times higher than that of LID solution and LID CLs (P<0.05). CLSM studies also confirmed that TAT-PLs reached viable layers of the skin. Hence, the results indicate that LID-TAT-PLs are effective and potential alternative for the LID transdermal formulation., (Copyright © 2012 Elsevier B.V. All rights reserved.)