Search

The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P =.001), 1.40 for Group III (P =.150), and 2.31 for Group IV (P <.001). Adiposity status in 2007 could predict hypertension (OR = 2.5, P <.001), as opposed to the initial adiposity status (P =.148). Subsequently adiposity status could have major effects on hypertension. Our society is very short of public health resources, particularly in developing countries, we should pay more attention to current adiposity status and encourage middle‐aged people to lose weight. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of peptide‐based drugs is commonly hampered by the intrinsic propensity to aggregation. A notable example is human calcitonin (hCT), a peptide hormone comprising 32 amino acids, which is synthesized and secreted by thyroid gland parafollicular cells (C cells). This hormone plays a vital role in regulating blood calcium levels and upholding bone integrity. Despite its physiological importance, utilizing hCT as a drug is hampered by its inclination to form amyloid. To address this limitation, an alternative is provided by salmon calcitonin (sCT), which possesses a lower aggregation propensity. Although sharing the same disulfide bond at the N terminus as hCT, sCT differs from hCT at a total of 16 amino acid positions. However, due to the dissimilarity in sequences, using sCT as a clinical replacement occasionally results in adverse side effects in patients. Earlier investigations have highlighted the significant roles of Tyr‐12 and Asn‐17 in inducing the formation of amyloid fibrils. By introducing double mutations at these sites, the ability to hinder aggregation can be significantly augmented. This study delves into the oligomerization and helical structure formation of the hCT double mutant (Y12LN17H hCT, noted as DM hCT), as well as two single mutants (Y12L and N17H), aiming to elucidate the mechanism behind hCT fibrillization. In addition, computational prediction tools were employed again to identify potential substitutes. Although the results yielded were not entirely satisfactory, a comparison between the newly examined and previously found hCT double mutants provides insights into the reduced aggregation propensity of the latter. This research endeavor holds the promise of informing the design of more effective therapeutic peptide drugs in the future. [ABSTRACT FROM AUTHOR]

Polymeric assemblies have emerged as a kind of promising platform in biomedical fields. The strong potency of polyphenols to form versatile interactions with other small or polymeric molecules via covalent and noncovalent linkages enables polyphenols to serve as molecular glues, offering a magic driving force to assemble multiple functional molecules into a diversity of polyphenol‐based systems, such as nanoparticles and hydrogels. Due to the unique merits of anti‐tumor, anti‐bacterial, antioxidant, anti‐inflammatory, and cardioprotective properties of polyphenols, polyphenol‐based systems hold great promise to deal with a wide spectrum of diseases. This review comprehensively overviews the components, intermolecular interactions, and preparation methods implicated in the assembly of polyphenol‐based systems. In addition, their medical applications are introduced, particularly the treatments of various diseases, such as tumors, bacterial infections, inflammatory bowel disease (IBD), cardiovascular diseases (CVDs), chronic periodontitis, acute lung injury, osteoarthritis, and renal fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: The myeloid‐derived suppressor cells (MDSCs) frequently have a high expansion in cancer patients. This research explored whether administration of β‐glucan could increase anti‐tumor immunity in oral squamous cell carcinoma (OSCC) patients. Materials and Methods: This study evaluated the MDSC level of circulating blood as CD33+/CD11b+/HLA‐DR‐/low by flow cytometry in 30 healthy donors (HDs, group I), in 48 oral squamous cell carcinoma (OSCC) patients before and after 14‐day preoperative administration of β‐glucan (group II), and in 52 OSCC patients without taking β‐glucan (group III). Results: A significantly higher mean MDSC level was observed in 100 OSCC patients than in 30 HDs (p <.001). There was a significant reduction of the mean MDSC level in group II patients after taking β‐glucan (p <.001). Moreover, we discovered a significantly higher recurrence‐free survival (RFS) in group II than in group III patients (p =.026). Finally, the multivariate Cox regression further identified the MDSC level ≤1% and administration of β‐glucan as more favorable prognostic factors for OSCC patients. Conclusion: Preoperative administration of β‐glucan can augment anti‐tumor immunity and increase RFS rate via subversion of suppressive function of MDSC in OSCC patients. [ABSTRACT FROM AUTHOR]

Taking inspiration from percutaneous ethanol injection (PEI) for tumor ablation, an acetaldehyde generator (SC@ZIF@ADH) is constructed for tumor treatment by modifying a metal–organic framework nanocarrier (ZIF), which is loaded with alcohol dehydrogenase (ADH), onto the surface of Saccharomyces cerevisiae (SC). Oral administration of SC@ZIF@ADH can target tumor via mannose‐mediated targeting to tumor associated macrophages (TAMs) and generate ethanol at the hypoxic tumor areas. Ethanol is subsequently catalyzed to toxic acetaldehyde by ADH, inducing tumor cells apoptosis and polarizing TAMs toward the anti‐tumor phenotype. In vivo animal results show that this acetaldehyde generator can cause a temulence‐like reaction in the tumor, significantly inhibiting tumor progression, and might provide an intelligent and nonsurgical substitute for PEI therapy. [ABSTRACT FROM AUTHOR]

Background: Nucleophosmin/nucleoplasmin family 1 (NPM1) has broad physiological functions, such as DNA replication, transcription, ribosome biogenesis, and centrosome replication. This study explored the clinicopathological importance of NPM1 as a prognostic marker for oral squamous cell carcinoma (OSCC). Methods: We collected specimens from 96 OSCC, 45 oral epithelial dysplasia (OED), and 29 normal oral mucosa (NOM). NPM1 expression was analyzed via immunohistochemistry. Correlations between NPM1and clinical parameters were analyzed using Student t test, chi‐squared test, and Kaplan‐Meier product‐limit method. Results: The NPM1 labeling indices (LIs) were significantly higher in OSCCs than in NOM and oral OED. Higher NPM1 expression was significantly correlated with larger tumor size, nodal metastasis, and advanced clinical stage. Multivariate analysis revealed that higher NPM1 LIs were an unfavorable independent factor for survival. Conclusions: Upregulated NPM1 is an independent biomarker of poor prognosis and NPM1 inhibitors may be promising in molecular targeted therapy against OSCC. [ABSTRACT FROM AUTHOR]

Two copper(I)‐based frameworks of complexes {[Cu(L)2(ClO4)]⋅CH3CN}(2) and {[Cu(L)(ClO4)]⋅ 2CH3CN} (3) (L = 1,3,5‐tris(4‐pyridylethynyl) benzene) were produced by reacting [Cu(MeCN)4(ClO4)] with different amounts of a ligand (L) using a hydrothermal method at temperatures of up to 130°C. The nitrogen atoms in the pyridine moieties of the ligand coordinate to the Cu(I) ion. The charge on the Cu(I) ion can be stabilized by extending the degree of conjugation in the system and by taking advantage of its highly symmetrical structure. The large degree of conjugation also supports numerous π–π interactions in the framework. [ABSTRACT FROM AUTHOR]

A reprogrammable transgenic mouse strain, called Col1a1 4F2A‐Oct4‐GFP, was bred for the present study. Because the somatic cells of this mouse strain contain only two copies of each Yamanaka factor, these animals are inefficient at producing induced pluripotent stem cells (iPSCs; approx. 0.005%) under traditional culture conditions. With an optimized culture condition, the iPSC production rate of mouse embryonic fibroblasts (MEFs) of Col1a1 4F2A‐Oct4‐GFP mice (MEFCol1a14F2A‐Oct4‐GFP) was increased to approximately 8%. Further, promotion of cell proliferation by serum supplementation did not enhance iPSC production. Inhibition of transforming growth factor β (TGF‐β) in the serum by SB431542 neither affected the growth rate of MEFCol1a14F2A‐Oct4‐GFP nor promoted iPSC production. However, the use of the gamma‐irradiated STO‐NEO‐LIF (γSNL) cells to serve as feeders for iPSC production resulted in a 5‐fold higher rate of iPSC production than the use of γMEFICR feeders. Interestingly, the use of SB431542 with the γMEFICR‐adopted system could eliminate this difference. RT‐PCR‐based comparative analysis further demonstrated that TGF‐β expression was 10‐fold higher in γMEFICR than in γSNL cells. Consistent with previous reports, mesenchymal to epithelial transition was found to participate in the initial steps of reprogramming in the specific context of MEFCol1a14F2A‐Oct4‐GFP. Moreover, we found that the initial seeding density is one of the pivotal factors for determining a high efficiency of iPSC generation. The iPSCs efficiently generated from our MEFCol1a14F2A‐Oct4‐GFP resembled mouse embryonic stem cells (mESCs) in aspects of teratoma formation and germline transmission. Depending on the culture conditions, our Col1a1 4F2A‐Oct4‐GFP mouse system can generate bona fide iPSCs with variable efficiencies, which can serve as a tool for interrogating the route taken by cells during somatic reprogramming. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the pharmacokinetic effect of silibinin on methadone in rats. Twenty‐four male Sprague–Dawley rats were randomly divided into 4 groups: control group, single dose of 100 mg/kg group, multiple doses of 100 mg/kg group, and multiple doses of 30 mg/kg group. A single dose of 6 mg/kg methadone was administrated to rats orally without or with silibinin. Plasma samples were collected via tail vein at different time points and concentrations of methadone and its metabolite, 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), were determined by ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Compared with the control group (without silibinin), both 30 and 100 mg/kg silibinin significantly increased the Cmax of methadone, but only 100 mg/kg silibinin significantly increased the AUC(0‐t) of methadone and decreased its clearance. Pharmacokinetics parameters of EDDP were not altered by 30 mg/kg silibinin; its Tmax was decreased by 100 mg/kg silibinin and the Cmax was increased by single dose of 100 mg/kg silibinin. It is concluded that silibinin significantly altered the pharmacokinetics of methadone in rats by increasing the exposure of methadone. Further investigations in human should be conducted. Therapeutic drug monitoring of methadone in individuals undergoing methadone maintenance therapy is recommended when silibinin is concomitant. [ABSTRACT FROM AUTHOR]

The association between central pulsatile hemodynamic load, arterial stiffness, and orthostatic hypotension (OH) is unclear. The authors recruited 1099 participants from the community. Questionnaire, physical examination, and laboratory tests were performed. To assess the correlation between central pulsatile hemodynamic load, arterial stiffness, and OH, multiple logistic regression analysis was performed, and the discriminatory power was assessed by the area under the receiver operating curve. The prevalence of OH in this population was 5.6%. After adjusting for potential confounders, brachial-ankle pulse wave velocity (BaPWV) was significantly and positively correlated with OH in both the hypertension and nonhypertension groups (all P<.05), while central systolic blood pressure (CSBP) was only significantly associated with OH in the hypertension subgroup. In addition, BaPWV seemed to have a better discriminatory power than CSBP in both subgroups. BaPWV appears to be a better indicator of OH than CSBP in routine clinical practice. [ABSTRACT FROM AUTHOR]

Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria‐based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio‐orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects. [ABSTRACT FROM AUTHOR]