Optimizing the time of doxil injection to increase the drug retention in transplanted murine mammary tumors

Sex hormonal milieus during the female fertility cycle modulate the tumor vascular permeability of breast cancer. It has been proposed that the liposomal formulated doxorubicin (ie, Doxil), given at the menstrual/estrous stage with the predicted highest tumor vascular permeability, allows significantly increased drug retention in the breast tumor. In the current study, syngeneic murine 4T1 mammary tumors were established on the backs of female BALB/c mice and Doxil was administered at particular mouse estrous cycle stages. The results indicated that Doxil administration during certain times in the mouse estrous cycle was crucial for drug retention in 4T1 tumor tissues. Significantly higher drug concentrations were detected in the tumor tissues when Doxil was administered during the diestrus stage, as compared to when the drug injection was given at all other estrous stages. Our study also showed that the tumor-bearing mice exhibited nearly normal rhythmicity of the estrous cycle post drug injection, indicating the feasibility of continual injection of Doxil at the same estrous cycle stage. By using 4T1 cells cultured in vitro, we showed that progesterone (P4) significantly inhibited cell proliferation and the production of six tumor-derived cytokines, eg, sTNF-RI, CXCL-16, GM-CSF, MIP-1α, MIP-1γ, and Flt3-L. Some of these factors have been shown to be vascular modulators in diverse tissues. In this report, we demonstrated that the concentration of P4 in the plasma and/or estrous cycle stage of 4T1 tumor-bearing mice can be used to select the best time for administrating the liposomal anticancer drugs

Mammaglobin as a potential molecular target for breast cancer drug delivery

<p>Abstract</p> <p>Background</p> <p>Mammaglobin (MAM) has been used as a specific molecular marker for breast cancer diagnosis. Recently, several groups of researchers proposed a number of therapeutic strategies targeting this molecule. Some of the strategies are based upon an essential but not demonstrated hypothesis – mammaglobin is associated with the surface of breast cancer cells, which strongly disputes the therapeutic strategies.</p> <p>Results</p> <p>We conducted a computer-based predictive analysis and identified a small fragment at the N-end of MAM as a potential transmembrane domain. We provided several evidences to demonstrate the presence of the membrane-associated MAM. We isolated the membrane protein components from known MAM positive breast cancer cells (MDA-MB361 and MDA-MB415). We showed that about 22–64% of MAM proteins, depending upon the types of the cancer cells, directly attached on the membrane of breast cancer cells, by Western blotting assays. To directly visualize the presence of the membrane-bound MAM protein, we incubated the MAM positive cancer cells with FITC labeled anti-MAM antibody, and observed clear fluorescent signals on the surface of the cells. In studying the MAM protein distribution in human breast cancer tissues, we first identified two immunostain patterns that are associated with the membrane-bound MAM: the membrane stain pattern and luminary surface stain pattern. To test whether the membrane-associated MAM can serve as a molecular target for drug delivery, we conjugated anti-MAM antibody to human low-density lipoprotein (LDL) and loaded doxorubicin (Dox) in the core of LDL. Specific binding and cytotoxicity of the MAM targeted and Dox loaded LDL was tested in the MAM positive breast cancer cells <it>in vitro</it>.</p> <p>Conclusion</p> <p>We first showed that some of MAM protein directly associated with the surface of breast cancer cells. The membrane-associated MAM protein may be utilized as a useful molecular marker for breast cancer targeted drug delivery.</p

An Analysis of Precipitation Extremes in the Inner Mongolian Plateau: Spatial-Temporal Patterns, Causes, and Implications

To improve how extreme events and climate variations are managed, there is a need to foster a deeper understanding of their interconnections. Consistent with this objective, this paper describes how precipitation extremes change both temporally and spatially in the Inner Mongolian Plateau (IMP), China and explains their causal factors. The paper refers to data collected from 43 meteorological stations in IMP and describes how precipitation extremes formed and how they influence agriculture. Data gathered and presented in this paper may be useful in understanding the extent to which the IMP is being influenced by global environmental change. This study reveals that the eleven precipitation extremes indices, except the number of precipitation days with over 0.5 mm (R0.5), number of heavy precipitation days (R10), and total precipitation in wet days (PRCPTOT), decreased in the IMP between 1959 and 2014, and most of them were non-significant in temporal. But the dry index has a larger magnitude decreasing trend than that of the wet indices, which can indicate that the dry situation was alleviated in IMP during the study interval. This study also indicated that precipitation extremes have strong relationships with elevation, latitude, and longitude. Atmospheric circulation and topography may be further primary reasons which result in the spatial variation characteristics in precipitation extremes over the IMP. Decreases in precipitation extremes, together with human activities such as livestock improvement and ecological restoration programs, has a positive effect in gross output value of agriculture and animal husbandry in the IMP. The results contribute to a deeper insight on the possible impacts of precipitation extremes and support the development of appropriate adaptation and mitigation strategies to cope with climate extremes. This paper further proposes science-based policies for grassland protection, agriculture, and animal husbandry on the national or regional and herdsman scales

Human Papillomavirus (HPV) Vaccine Uptake and the Willingness to Receive the HPV Vaccination among Female College Students in China: A Multicenter Study

Background: This study aimed to determine human papillomavirus (HPV) vaccine uptake and willingness to receive HPV vaccination among female college students, in China, and its associated factors. Methods: An online cross-sectional survey of female college students across the eastern, central, and western regions of China was undertaken between April and September 2019. Partial least squares structural equation modeling (PLS-SEM) was used to examine factors associated with the HPV vaccine uptake and willingness to receive the HPV vaccine. Results: Among the total 4220 students who participated in this study, 11.0% reported having been vaccinated against HPV. There are direct effects of indicators of higher socioeconomic status, older age (β = 0.084 and p = 0.006), and geographical region (residing in Eastern China, β = 0.033, and p = 0.024) on HPV vaccine uptake. Higher knowledge (β = 0.062 and p < 0.000) and perceived susceptibility (β = 0.043 and p = 0.002) were also predictors of HPV vaccine uptake. Of those who had not received the HPV vaccine, 53.5% expressed a willingness to do so. Likewise, social economic status indicators were associated with the willingness to receive the HPV vaccine. Total knowledge score (β = 0.138 and p < 0.001), both perceived susceptibility (β = 0.092 and p < 0.001) and perceived benefit (β = 0.088 and p < 0.001), and sexual experience (β = 0.041 and p = 0.007) had a positive and significant direct effect on the willingness to receive the HPV vaccine, while perceived barriers (β = −0.071 and p < 0.001) had a negative effect on the willingness to receive the HPV vaccine. Conclusions: Geographical region and socioeconomic disparities in the HPV vaccination uptake rate and willingness to receive the HPV vaccine provide valuable information for public health planning that aims to improve vaccination rates in underserved areas in China. The influence of knowledge and perceptions of HPV vaccination suggests the importance of communication for HPV immunization

EFFECTS OF LONG-TERM TAI CHI EXERCISE ON BALANCE CONTROL IN OLDER ADULTS

This study assessed the static and dynamic balance control of older adults who have 10 years of Tai Chi exercise experience and compared their characteristics with their sedentary counterparts. The abilities were measured using methods: single-leg stance times with eyes open and closed; sway of center of pressure (COP) during static standing with eyes open/closed, and leaning the body in three specific directions. Compared with control group, 1) Tai Chi Group showed longer single-leg stance times with eyes open and closed, 2) slower sway velocity of COP in mediolateral and anterioposterior directions and shorter sway distance in both directions, and 3) shorter total, anterioposterior, and mediolateral routes and shorter time spent during the dynamic balance test. Long-term Tai Chi exercise improves the balance ability, especially the dynamic balance, of older adults

Impact of stress hyperglycemia ratio on mortality in patients with cardiac arrest: insight from American MIMIC-IV database

BackgroundStress hyperglycemia ratio (SHR) has shown a predominant correlation with transient adverse events in critically ill patients. However, there remains a gap in comprehensive research regarding the association between SHR and mortality among patients experiencing cardiac arrest and admitted to the intensive care unit (ICU).MethodsA total of 535 patients with their initial ICU admission suffered cardiac arrest, according to the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were stratified into four categories based on quantiles of SHR. Multivariable Cox regression models were used to evaluate the association SHR and mortality. The association between SHR and mortality was assessed using multivariable Cox regression models. Subgroup analyses were conducted to determine whether SHR influenced ICU, 1-year, and long-term all-cause mortality in subgroups stratified according to diabetes status.ResultsPatients with higher SHR, when compared to the reference quartile 1 group, exhibited a greater risk of ICU mortality (adjusted hazard ratio [aHR] = 3.029; 95% CI: 1.802-5.090), 1-year mortality (aHR = 3.057; 95% CI: 1.885-4.958), and long-term mortality (aHR = 3.183; 95% CI: 2.020-5.015). This association was particularly noteworthy among patients without diabetes, as indicated by subgroup analysis.ConclusionElevated SHR was notably associated with heightened risks of ICU, 1-year, and long-term all-cause mortality among cardiac arrest patients. These findings underscore the importance of considering SHR as a potential prognostic factor in the critical care management of cardiac arrest patients, warranting further investigation and clinical attention