Search Results (409)

From the first report in 1891 by Dr. Coley of the effective treatment of tumors in 1000 patients with Streptococcus and the first successful use of bacterial vectors for transferring therapeutic genes in 1980 by Dr. Schnaffer, bactofection has been shown to be a promising strategy in the fields of vaccination, gene therapy, and cancer therapy. This review describes the general theory of bactofection and its advantages, disadvantages, challenges, and expectations, compiling the most notable advances in 14 vaccination studies, 27 cancer therapy studies, and 13 clinical trials. It also describes the current scope of bactofection and promising results. The extensive knowledge of Salmonella biology, as well as the multiple adequacies of the Ty21a vaccination platform, has allowed notable developments worldwide that have mainly been reflected in therapeutic efforts against cancer. In this regard, we strongly recommend the creation of a recombinant Ty21a model that constitutively expresses the GtgE protease from S. typhimurium, allowing this vector to be used in animal trials, thus enhancing the likelihood of favorable results that could quickly transition to clinical trials. From the current perspective, it is necessary to explore a greater diversity of bacterial vectors and find the best combination of implemented attenuations, generating personalized models that guarantee the maximum effectiveness in cancer therapy and vaccination. Full article

This article presents a detailed analysis of a unique item from the author’s family archive: the work diary of his grandfather, Mordechai Livnat (Libman). In this diary, Livnat meticulously recorded, between 1928 and 1931, the details of his work as an agricultural laborer in Herzliya—at the time, a small village in the central part of Eretz Israel (aka pre-State Israel)—primarily during the establishment of the new colony’s citrus orchards. The diary documents employment details, employer information, working hours, and wages received. Quantitative and qualitative analyses of the information contained in the diary paint a comprehensive picture that allows us to learn about the lives of Jewish agricultural laborers in Eretz Israel at that time. In particular, the hardships faced by these workers stand out, primarily job insecurity, which manifested mainly in their dependence on the weather and the need to work for multiple employers. This article also sheds light on aspects related to agricultural work before the introduction of technological advancements to the agricultural sector, which was mainly manual then, and its impact on the daily routine of the agricultural laborer. The diary is analyzed using an inductive approach—from the text outwards—in a way that emphasizes the complexity and importance of the connections between the macro and micro in historical research. This way, it is demonstrated how items collected during genealogy research can shed important light on historical knowledge, and not just the other way around. Full article

Extracts from Jamaica flowers (Hibiscus sabdariffa) from Morelia (Mexico) were evaluated as antidiabetic ingredients in a diabetic rat lab model for 80 days at doses of 200, 400, and 600 mg extract/kg rat weight. The hydroalcoholic extract (water:ethanol 80:20 (v/v) at 50 °C) showed a TPC value of 403.28 ± 7.71 mg GAE/g extract, and an antioxidant activity of 0.219 ± 0.00003 mmol Trolox/g (ABTS) and 0.134 ± 0.00001 mmol Trolox/g (DPPH). The extract allowed reducing the diabetic glucose plasma levels under fasting conditions in a dose-dependent manner by 35.2%, 41.63%, and 50.1%. Additionally, the highest dose of the extract (600 mg/kg) slightly reduced the short-term postprandial glucose response while improving the long-term response, reducing hyperglycemia by 45.1%. The same dose also improved lipid metabolism by reducing total cholesterol, triglycerides, VLDL, and LDL, while the HDL level increased. The improvement in glucose and lipid management in the treated groups also led to reduced levels of glycosylated hemoglobin, as well as lower insulin resistance (TyG index), compared to the diabetic control group. The results of this study suggest that extracts from Hibiscus sabdariffa (Morelia) can be used as potential functional ingredients or nutraceuticals for managing the diabetic condition. Full article

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m², glycated hemoglobin A1C (HbA_1c) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T₀), 1 h after lunch (T₁) and 8 h after baseline (T₂). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 (p = 0.014), TG (p = 0.012), TC (p = 0.017), HDL-C (p = 0.020), LDL-C (p = 0.021), albumin (p = 0.003), total protein (p = 0.021), and uric acid (p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP (p = 0.529), creatinine (p = 0.199), TyG (p = 0.331), and the lipid ratios TG/HDL-C (p = 0.793) and TC/HDL-C (p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity. Full article

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial–mesenchymal transition (EMT) markers. Full article

Prosthechea karwinskii is an endemic orchid of Mexico with cultural significance for its ornamental, food, religious, and medicinal uses. In traditional medicine, diabetic patients use the leaves of this plant to lower glucose levels. The present study evaluated the effect of P. karwinskii leaves extract on the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance for its nutraceutical potential to reduce insulin resistance and oxidative stress. Obesity and insulin resistance were induced with 40% sucrose in water for 20 weeks. Four groups (control rats, obese rats, obese rats administered the extract, and obese rats administered metformin) were evaluated. Extract compounds were identified by UHPLC-ESI-qTOF-MS/MS. Glucose, insulin, triglyceride, and insulin resistance indices (HOMA-IR and TyG), as well as the activity of the antioxidant enzymes, increased in rats in the obese group. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride, and insulin resistance indices and antioxidant enzyme activity to values similar to those of the control group. Therefore, this study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of dietary supplements or functional foods to help treat diseases whose pathophysiology is related to oxidative stress and insulin resistance. Full article

Climatic change and environmental degradation have become a worldwide discourse. Green innovation is commonly viewed as a means of lowering environmental pollution in the era of climate change. Considering this, the primary purpose of this study is to investigate the effects of environmental technology (ET) on CO₂ emissions by controlling Saudi Arabia’s ICT use, energy use, energy intensity, and financial development. It uses a quantile-based multiple-threshold “nonlinear autoregressive distributed lag (NARDL)” estimation utilizing data from 1990 to 2020. It also conducts the ARDL and NARDL estimation techniques simultaneously for comparative outcomes. The Toda–Yamamoto (T-Y) causality assessment also crosschecks the primary multiple-threshold NARDL estimates. The outcomes reveal that ET promotes environmental pollution due to its low scale compared to the Kingdom’s technological base. ICT improves environmental quality, and energy consumption deteriorates it. All three estimation techniques confirm these findings. The multiple-threshold NARDL estimation appears robust and reveals damaging impacts of energy intensity and financial development on emissions. The T-Y causality assessment also authenticates the primary estimation outcomes. The outcomes have important implications for policymakers to focus on enhancing patents for ET, raising ICT diffusion, reducing energy intensity through generating more renewable energies, expanding financial support for ICT and green investments, and ensuring a sustainable environment. Full article

Partus mentis (the parturition of the mind) brings together the following two significant aspects of Romantic culture and ideology: the exploration into human generation, and the process of how imagination forms an idea and makes the mind creatively productive. This article suggests that analyzing William Blake’s portrayal of imagination through the partus mentis trope can enhance our comprehension of how he illustrates and employs this faculty in his works. In Blake’s partus mentis, the analogy between the brain and the womb is pivotal. The brain is seen as a host for ideas that are conceived through imagination, and once they are brought to life, they become art. This is a vital component of Blake’s cosmogony, tying into his personal reinterpretation of biblical Genesis and his concept of the Human Form Divine. It also includes his response to medical theories and practises regarding generation and life. This article pays close attention to the medico-cultural discourse that was contemporary to Blake, and its wide use of the ‘analogy’, which defined the episteme of the long eighteenth century. The analogy approach was later challenged by the ‘epistemology of the visual’, which emphasized the use of anatomical atlases, wax models, and dissections for direct experiential insights into bodily functions and processes, particularly of the brain and the womb. This article argues that Blake is able to transcend these two epistemologies while harnessing specific elements from each. Full article

Tomato (Solanum lycopersicum L.) is a crop that is affected by more than a hundred viral species. De la pera is a local varietal type of tomato that is very popular in southeastern Spain. However, it is highly susceptible to several viruses, such as Tomato yellow leaf curl virus (TYLCV), which is considered one of the most important diseases of tomato crops and is a limiting factor for production in both outdoor and protected crops, making it difficult to eradicate. This study shows the effect of gene introgression on the performance of traditional lines of De la pera by combining two genes that offer tolerance to TYLCV, Ty-1 and ty-5, on some yield and quality traits and on the antioxidant capacity of tomato fruits. Two pear tomato breeding families, UMH175 and UMH220, were evaluated. Four lines from each of the families with all homozygous combinations of the Ty-1 and ty-5 genes were studied. The results showed that the introgression of the ty-5 allele produced a slight negative effect on yield, mean fruit weight, total soluble solids, and titratable acidity, in contrast to Ty-1, which produced a large negative effect. None of the introgressions showed a negative effect on the antioxidant compounds. ty-5 is a promising gene for use in breeding programs. Full article

Low-alloyed Mg–Li–Er alloys were developed in this study and a bimodal-grained structure was obtained by varying the trace Er content and extrusion temperature. The alloys displayed a good strength–ductility synergy, i.e., a tensile yield strength (TYS) of 270 MPa and an elongation (EL) of 19.1%. Microstructural characterization revealed that the formation of numerous submicron Mg₂₄Er₅ particles favored a high density of low-angle grain boundaries (LAGBs) inside the deformed grains and inhibited dynamic recrystallization (DRX). The resultant coarse unDRXed grains with a strong basal texture and considerable LAGBs, together with the fine DRXed grains, contributed to the high strength–ductility synergy. Full article

The Mg-Al-RE series heat-resistant magnesium alloys are applied in automotive engine and transmission system components due to their high-temperature performance. However, after serving at a high temperature for a long time, the Al₁₁RE₃ phase coarsened and even decomposed, while the Mg₁₇Al₁₂ phase grew and dissolved, which limits the service temperature of Mg-Al-RE series heat-resistant magnesium alloys to a maximum of 175 °C. In this study, a new preparation method for in situ AlN particles was presented. The AlN/Mg-4Al-4La-0.3Mn composites were prepared by a master alloy and casting method. The effects of various contents of AlN (0.5–3.0 wt.%) on the microstructure and mechanical properties of the Mg-4Al-4La-0.3Mn (AE44) alloy at room (25 °C) and high temperatures (150–250 °C) were investigated. Microstructure analysis revealed that the inclusion of AlN led to a reduction in both the grain size and second phase size in the AE44 alloy, while also improving the distribution of the second phase. The average grain size, Al₁₁La₃ phase, Al₂La phase, and Al₃La phase of the 2.0 wt.% AlN/AE44 composite were 135.7, 9.6, 1.9, and 12.6 μm, respectively, which were significantly lower than those of the AE44 matrix alloy (179.8, 12.6, 3.3, 17.8 μm). The refinement was attributed to the ability of AlN particles to serve as heterogeneous nucleation cores for α-Mg and, at the same time, impede the growth of the solid–liquid interface, eventually leading to grain refinement. With the increase in the AlN content, the mechanical properties of composites initially exhibited an increase at both room and high temperatures, followed by a subsequent decrease. When the AlN content was 2.0 wt.%, the composite exhibited optimal strength and plasticity matching. At room temperature, the TYS, UTS, and EL values of the 2.0 wt.% Mg-4Al-4La-0.3Mn composite were 96 MPa, 175 MPa, and 7.0%, respectively, which were increased by 26 MPa, 27 MPa, and 0.7% when compared with the base alloy. The TYS of the 2.0 wt.% Mg-4Al-4La-0.3Mn composite at 150 °C, 200 °C, and 250 °C were 17 MPa, 14 MPa, and 22 MPa higher than those of the matrix alloy, respectively. The main strengthening mechanisms were second phase strengthening, load transfer strengthening, and thermal mismatch strengthening. At elevated temperatures, AlN particles effectively pinned the grain boundaries, inhibiting their migration, and hindered dislocation climbing, resulting in excellent mechanical properties of the composites at high temperatures. This study contributes to the advancement of in situ AlN particle preparation methods and the exploration of effects of AlN on the properties and microstructure of Mg-Al-RE alloys at high temperatures (150–250 °C). Full article

Background/Objectives: Insulin resistance is crucial in the pathogenesis of Metabolic Syndrome (MetS), type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride–glucose index (TyG index), a validated measure of insulin resistance, also predicts MetS, T2DM, the severity of albuminuria and ASCVD. There are scant data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acid (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Methods: Participants (n = 102) included 59 patients with MetS and 43 controls. People with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver Operating Characteristic (ROC) curve analysis revealed that the TyG index was an excellent predictor of MetS with an area under the curve of 0.87, and it correlated with both hepatic and adipose tissue insulin resistance. Both serum RBP-4 levels and non-HDL cholesterol increased significantly over tertiles of the TyG index. Based on the TyG index tertiles and/or correlations, oxidized LDL, nitrotyrosine, C-reactive protein, endotoxin, chemerin, interleukin-6 levels and monocyte toll-like receptor (TLR)-4 and TLR-2 and their cellular signaling were significantly associated with the TyG index. Conclusions: Increased non-HDL-C and, most importantly, a pro-inflammatory and pro-oxidant state could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD with an increasing TyG index. Full article

Cereal + legume rotation is an integrated system that facilitates soil fertility and sustainable agricultural production. However, research on the management compatibility affecting soil physico-chemical properties yields overall agro-ecosystem sustainability, but profitability is lacking, especially under straw retention and potential reductions in fertilizer application. An 11-year field experiment investigated three treatments: no straw retention + traditional mineral fertilization (TNS), straw retention + traditional mineral fertilization (TS), and straw retention + reduced mineral fertilization (DS). Compared with TNS, TS significantly improved soil physico-chemical properties, including macro-aggregates (R > 0.25 mm), porosity, field water capacity (FWC), soil organic carbon (SOC) storage, total nitrogen storage, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) by 17.3%, 3.2%, 13.0%, 5.5%, 3.2%, 15.5%, and 13.8%, respectively. TS also significantly increased total (wheat + soybean) yields (TYs), economic profits, and emergy sustainability index (ESI) by 15.8%, 25.0%, 3.7 times that of TNS, respectively. Surprisingly, compared with TS, DS further significantly improved R > 0.25 mm, porosity, FWC, SOC storage, MBC, MBN, TY, economic profits, and ESI by 11.4%, 1.5%, 6.1%, 3.0%, 10.6%, 7.2%, 5.7%, 11.1%, and 36.5%, respectively. Overall, retaining straw with reduced fertilization enhances soil properties, yields, and emergy sustainability in wheat–soybean rotation systems. Full article

The Roma population is Europe’s largest ethnic minority, yet data on the prevalence of non-communicable diseases remain scarce in medical literature. This study aimed to compare the clinical and metabolic particularities of a Roma population with diabetes with a group of non-Roma. We conducted an observational, transversal study and evaluated 808 adult patients with diabetes mellitus, from a tertiary diabetes care hospital. The prevalence of metabolic syndrome was high among both groups, 94.3% in the Roma patients and 89.1% in the non-Roma. A slightly higher mean value of the triglyceride–glucose (TyG) index was observed among the Roma group (10.07 ± 0.71 versus 9.71 ± 0.82). Among the non-Roma, variables that were significantly associated with the TyG index were glycated hemoglobin (HbA1c), total cholesterol (TC), high density lipoprotein–cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), while among the Roma, HbA1c and HDL-c were correlated with this index. There were no differences concerning myocardial infarction; however, the number of patients with a history of stroke was 2.1 times higher in the Roma group compared to the non-Roma group. The prevalence of cardiovascular risk factors, cardiovascular disease, and microvascular complications among the study’s Roma population are quite significant, underscoring the importance of ethnic disparities in approaching healthcare management strategies. Full article

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20–39 and 40–59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20–39 and triglyceride–glucose index (TyG) in those aged 40–59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level. Full article