The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CARs) is that they are in fact heterogeneous mixtures of different CARs families, and are named according to the thickening purpose of the product which does not reflect the real com-position. Consequently, this can limit their use in a clinical grade. To address this issue, six commercial λ-CARs were compared for which differences in their physiochemical properties were shown. Then, a H2O2-assissed radical depolymerization was applied to each commercial source and the number and weight averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in term of molar masses and DS, that ranged within previously reported values suitable for anti-tumor proper-ties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed indeed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, but also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumor recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumor dissemination and regrowth. One current aim of GBM research focusses on assessing anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and focal adhesion dynamics. By determining the migrastatic activity of Turmeric, Indigo and Magnolia on GBM cell migration, we demonstrate a potential role for Turmeric as a novel GBM anti-migratory therapeutic, in combination with the current standard of care, to prevent tumor recurrence and promote patient survival.

Since the beginning of the 21st century, Romanian migrants have become one of the most significant national groups doing agricultural work in Spain, initially coming via a temporary migration program and later under several different modalities. However, despite their critical importance for the functioning of Europe’s largest agro-industry, the study of this long-term circular mobility is still underdeveloped in migration and agriculture literature. Thanks to extensive fieldwork carried out in the provinces of Huelva and Lleida in Spain and in the counties of Teleorman and Buzău in Romania, this paper has two main objectives: first, to identify some of the most common forms of mobility of these migrants and second, to discuss whether this industrial agriculture, hugely dependent on migrant work, is socially sustainable. The case of Romanian migrants in Spanish agriculture will serve to show how a critical sector for the EU and for the 2030 Agenda for Sustainable Development of the United Nations, operates on an unsustainable model based on precariousness and exploitation.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared to normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate utilizing several cell lines from the breast and lung. Initial screening was done in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of growth media used. Given the paradigm-shifting nature of our discovery, we pursued possible mechanisms responsible. Neither mass, cell doubling, nor volume, accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased ATP at premigratory-wound induction – but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

The authors argue that despite significant numbers of foreign workers present in the Russian labor market Russia remains unattractive for highly skilled foreign workers. The economic crisis the country has faced since 2014 has resulted in a further outflow of foreign nationals from OECD countries. So Russia has to look for employees among newcomers from the former Soviet states, the majority of whom come from Central Asia. Russian politics with regard to immigration is characterized by the collision between “geopolitical” and domestic policy rationales. On one hand, seeking to maximize its influence in the post-Soviet space Russia provides preferential conditions of employment for citizens of partner countries in the framework of the Eurasian Economic Union. On the other hand, the Kremlin is afraid to liberalize its approach to immigration and the integration of immigrants through fear of losing popularity among the electorate. The second substantial feature of Russian immigration politics is an extreme level of securitization of migration issues. The government considers these issues primarily through a policing lens. One cannot claim that the Russian state does not take any steps to liberalize “migratory regulation”; however, the effect of these measures is being vastly reduced by new restrictions. In addition, liberally designed laws do not bring the expected results due to the corrupt practices that pervade the whole of migration regulation.

In the year in which the world "stopped" due to the pandemic, many people didn't have that option and had to keep moving as the only alternative to survive. One of the main destinations in South America, during the quarantine measures established around the world, was Brazil, especially because of the crisis Venezuela went through in the second half of the 2010s. Throughout the research, we observed measures that were applied by the Brazilian government on the grounds of public health issues or cases of health risks related to COVID-19. An analysis of the first measures published by the Brazilian government reveals an effort to securitize borders, which at the same time restricted the government's responsibility to fulfil its role of protecting migrants in need.

Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

Dual specificity phosphatase 2 (DUSP2) regulates the activation of members in the mitogen-activated protein kinase (MAPK) family, which is involved in a variety of cellular processes like cell proliferation, differentiation, apoptosis and migration. DUSP2 also regulates the expression of inflammatory mediators in macrophages, however, it remains unknown whether DUSP2 participates in macrophage migration. Here, using the tail fin injury model in zebrafish larvae, we found that deletion of DUSP2 inhibited expression of pro-inflammatory cytokines and macrophage chemokines. Moreover, live imaging results showed that migration of macrophages to the injury site was inhibited after DUSP2 deletion. This inhibitory effect was mediated through reduced activation of extracellular regulated protein kinases (ERK) in DUSP2 knockout zebrafish.

Albanian migration has always reflected a family character, be that before 1945 when Albania was not yet completely isolated, as well as after 1990 when borders were reopened. This feature characterized all types of movement, internal or international, permanent or seasonal migration, return migration or transnational movements, and remigration. The role of the family has been very important in making decisions regarding migration and answering questions from why to how to migrate, from when to where, whom to ask for help or how to invest remittances. Based on the case study of a rural area in Northern Albania, The Administrative Unit of Dajç, this article explores in detail the roles of family and kinship on decisions regarding return migration, the re-adjustment process, remigration or transnational life. By exploring the role of the family context in remigration and vice-versa the article reflects that the family biography – including the lifestyle, plans for the future or expectations - has changed due to previous migration experiences or challenges and difficulties when returning to the home country. It demonstrates how individual decisions to migrate or to ‘return home’ are negotiated and supported within families making transnational life a family project. The article adopts a new approach in the Albanian Migration Studies which may be implied on broader areas for further research in the future.

International migrants comprised 14% of the UK population in 2020, but migrant health in the UK has rarely been studied at a population level using primary care electronic health records (EHRs). Given the difficulty of determining migration status using EHRs, this study developed a migration phenotype and assessed its validity. We developed a phenotyping algorithm using codes for country of birth, visa status, non-English main/first language and non-UK origin. It was applied to a Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country of birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997-2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified using the phenotype. 178,749 (1.11%) of these migrants were identified by codes indicating foreign country of birth or visa status, 216,731 (1.35%) a non-English main/first language, and 8,288 (0.05%) non-UK origin. The cohort was similarly distributed compared to ONS migration statistics in terms of sex and region of birth. Recording of migration improved from identifying approximately one-tenth of the expected proportion of migrants according to the ONS in 2004 to a quarter in 2018. Younger migrants were better represented than those aged 50 and over. The migration phenotype identified a large number of migrants and can be used to undertake large-scale migration health research in CPRD GOLD to inform healthcare policy, practice and action. While the cohort was representative of the UK migrant population in terms of sex and region of birth, migration status was under-recorded in earlier years and older ages, and future studies for these groups should therefore be interpreted with caution.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

SETD7 is a member of the SET domain-containing lysine methyltransferase family and is a crucial component in the development and spread of a number of human cancers. However, the specific function of the SETD7 gene in ovarian cancer (OC) is still unclear. The purpose of this research was to elucidate the expression and role of SETD7 in OC. In comparison to normal controls, OC tissues (83%, 73/88) and cell lines exhibited higher protein levels of SETD7 (p < 0.001). High SETD7 protein levels were substantially correlated with M category (p = 0.019) and FIGO stage (p = 0.021). Furthermore, the high mRNA levels of SETD7 were correlated to poor progression-free survival (PFS) in all patients and serous patients with OC (p < 0.05). Importantly, the biological function experiments showed that SETD7 behaved as an oncogene in OC by dramatically facilitating the proliferation and migration of A2780 and SKOV3 cells. Additionally, SETD7 might promote cell migration via accelerating the EMT process in A2780 and SKOV3 cells. Our findings reveal that SETD7 may be a valuable molecular marker for identifying and anticipating the development of OC.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Ferruginol is a promising abietane-type antitumor diterpene able to induce apoptosis in SK-Mel-28 human malignant melanoma. We here aim to increase this activity by testing the effect of a small library of ferruginol analogues. After an screening of their antiproliferative activity (SRB staining) on SK-Mel-28 cells the analogue 18-aminoferruginol (GI50=10 µM) was further selected for mechanistic studies including effects on mitochondrial viability (MTT assay, IC50=10 µM p<0.0001), induction of apoptosis (DAPI staining, p<0.001), changes in cell morphology associated with the treatment (cell shrinkage and membrane blebbing), induction of caspase-3/7 activity (2.5x at 48h, 6.5x at 72h; p<0.0001), changes in the mitochondrial membrane potential (not significant), and effects on 2D cell migration and 3D cell invasion (modified Boyden assay, not significant). The results were compared to those of the parent molecule (ferruginol, GI50»50 µM) and paclitaxel (GI50=10 nM) as a reference drug. In conclusion, we demonstrate here that derivatization of ferruginol into 18-aminoferruginol increases its antiproliferative activity 5 times in SK-MEL-28 cells as well as changing the apoptotic mechanism of its parent molecule ferruginol from activation of caspases without depolarization of mitochondrial membrane.

Changing mobility patterns combined with changes in the climate present challenges and opportunities for global health, requiring effective, relevant and humane policy responses. This study used data from a systematic literature review that examined the intersection between climate change, migration and health. The aim of the present study was to synthesize policy recommendations in the peer-reviewed literature, regarding this type of environmental migration with respect to health, to strengthen the evidence-base. Systematic searches were conducted in four academic databases (PubMed, Ovid Medline, Global Health and Scopus) and Google Scholar for empirical studies published between 1990 – 2020 that used any study design to investigate migration and health in the context of climate change. Studies underwent a two-stage protocol-based screening process and eligible studies were appraised for quality using a standardized mixed-methods tool. From the initial 2,425 hits, 68 articles were appraised for quality and included in the synthesis. Among the policy recommendations, six themes were discernible: (1) avoid the universal promotion of migration as an adaptive response to climate risk; (2) preserve cultural and social ties of mobile populations; (3) enable the participation of migrants in decision-making in sites of relocation and resettlement; (4) strengthen health systems and reduce barriers for migrant access to health care; (5) support and promote optimization of social determinants of migrant health; (6) integrate health into loss and damage assessments related to climate change. The results call for transformative policies that support the health and wellbeing of people engaging in, or affected by mobility responses, including those whose migration decisions and experiences are influenced by climate change, and to establish and develop inclusive migrant healthcare.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

The migration paths and distribution driving factors of heavy metals in dry and windy area polluted by their production in the North China need a further research. To address this research gap, we collected 675 soil samples, 72 atmospheric deposition samples and 20 water samples around a production area and measured its heavy metal concentrations. Results showed that the Cu, Zn, As and Pb in 0-10 cm soil layer showed a fan-shaped distribution, which was consistent with their atmospheric deposition fluxes. It indicated the distribution patterns of these heavy metals were driven by strong winds in studied area. Although Cr concentrated to the production area in the 0-10 cm soil layer, principal component analysis showed that this migration was through wind as well. The concentration of Cd in the river increased from 0.257 mg/L to 0.460 mg/L along water flowing, and caused the same distribution trend in soil near the river from upstream to downstream. Unlike the above, surface runoff should drive the Cd migration. The concentration of Pb in the river was over threshold of pollution, and also led to an accumulation in the 5-10 cm soil layer. It suggested that the migration of Pb was through both wind and surface runoff. Six studied heavy metals showed different migration behaviors, and specific control strategies for individual heavy metal should be concerned.

Lung cancer is a prevalent and aggressive neoplasm worldwide, contributing to significant mortality rates. Dehydroepiandrosterone (DHEA) constitutes the bulk of the steroid hormone in human plasma, has a robust antiproliferative effect, and induces cell death in various tumor cells. However, its role in lung cancer cells remains unexplored. This study aimed to investigate the influence of DHEA on the proliferation, viability, autophagy, and migration of several lung cancer cell lines, including A549, HCC827, and NCI-H2347. Cell proliferation was assessed through crystal violet staining; cell number and viability were evaluated using trypan blue staining; viability was confirmed by MTT reduction, a method that is also an indicator of metabolic activity; migration was assessed via a wound healing assay. Autophagy was evaluated using a specific kit, while cell death was determined by annexin-V-FITC/propidium iodide staining and caspase-3/7 activity assay. The results indicate that DHEA significantly reduced proliferation, cell number, metabolic activity, and migration in all examined lung tumor cells. These effects correlate with an increased autophagy induced by DHEA. No signs of apoptosis or necrosis were observed across the range of DHEA concentrations used. Although these findings are preliminary, they suggest that DHEA could hold promise as an alternative treatment option for various subtypes of lung cancer.

Abstract: The migration and transformation of pesticides in the environment will have an impact on the ecosystem. This study collected greenhouse soil from Shouguang, Shandong Province, and studied the photodegradation and leaching of 17 common pesticides in the soil. The results of photodegradation experiments showed that the degradation rate of certain pesticides was increased in the light environment, compared with that in the dark controls. The light half-lives of emamectin benzoate, pyraclostrobin, and metalaxyl were all shorter than their respective dark half-lives, indicating that their residues in soil were greatly affected by light. The leaching experiment showed that the leaching potential of the leachable pesticides was: nitenpyram ≫ metalaxyl &gt; acetamiprid &gt; carbendazim &gt; diethofencarb ≈ chlorantraniliprole &gt; isoprothiolane &gt; oxadixyl &gt; boscalid ≈ tebuconazole &gt; hexaconazole. Pesticides that are easy to leach but not easy to degrade, such as chlorantraniliprole and metalaxyl, have a high potential risk of groundwater pollution, and more degradation technologies should be used to reduce their pollution risk. The study on photodegradation and vertical migration behavior of various pesticides in this study was conducive to providing references for the agricultural use and pollution control of pesticides.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

The migratory life history of anadromous salmonids requires successful migration between nursery, feeding and spawning habitats. Smoltification is the major transformation anadromous salmonids undergo before migration to feeding areas and prepares juvenile fish for downstream migration and entry to seawater. We reviewed the effects of climate change on smolt ecology from growth of juveniles in freshwater to early post-smolts in sea. Shift in the suitable thermal conditions by climate change is causing Atlantic salmon to expand their range northwards, while in the southern edge of their distribution populations struggle with high temperatures and occasional droughts. Climatic conditions, particularly warmer temperatures, are affecting growth during freshwater phase in the river. Better growth in the northern latitudes leads to earlier smoltification. Thermal refuges, the areas of cooler water in the river, are especially important for salmonids impacted by climate change. Restoring and maintaining connectivity and suitable diverse mosaic habitat in rivers are important for survival and growth throughout the range. The start of the smolt migration has shifted earlier as a response to increasing water temperatures, which has led to concerns of mismatch with optimal conditions for post-smolts in the sea decreasing their survival. A wide smolt window allowing all migrating phenotypes from early to late migrant’s safe access to sea is important in changing environmental conditions. This is true also for regulated rivers, where flow regulation practices cause selection pressures on migrating salmonid phenotypes. Life history in freshwater affects also marine survival, and there is a need for better collaboration across life stages and habitats among researchers and managers to boost the smolt production in rivers.

This study was conducted to identify soil cadmium (Cd) removal pathways and their contribution rates during phytoremediation by Pennisetum hybridum, as well as to comprehensively assess its phytoremediation potential. Multilayered soil column tests and farmland simulating lysimeter tests were conducted to investigate the Cd phytoextraction and migration patterns in topsoil and subsoil simultaneously. The aboveground annual yield of P. hybridum grown in the lysimeter was 206 ton·ha–1. The total amount of Cd extracted in P. hybridum shoots was 234 g·ha–1, which was similar to that of other typical phytoremediation plants. After the test, the topsoil Cd removal rate was 21.50%–35.81%, whereas the extraction efficiency in P. hybridum shoots was only 4.17%–8.53%. These findings indicate that extraction by plant shoots was not the most important contributor to the decrease of Cd in the topsoil. The proportions of Cd retained by root cell wall was approximately 50% of the total Cd in root. Based on column test results, P. hybridum treatment led to a significant decrease in soil pH and considerably enhanced Cd migration to subsoil and groundwater. P. hybridum decreases Cd in the topsoil through multiple pathways and provides a relatively ideal material for phytoremediation of Cd-contaminated soils.

Background: Mental health is a growing concern worldwide. It is not well understood whether Nepali workers, including international labour migrants from Nepal, are at higher risk of developing mental health problems. The purpose of our study is to determine the prevalence of and examine the risks factors for depression among returnee migrants and non-migrant working male adults in Nepal. Methods: A cross-sectional survey of a probability-based sample of 725 participants was conducted in February 2020. The sample was comprised of two groups based on migration status: returning migrants and non-migrants. Logistic regression was applied to investigate factors associated with symptoms depression.Results: The overall prevalence of depression was 10.1%. However, the prevalence of depression was lower (7%) among returnee migrants compared to non-migrants (13.7%). Participants in the lower income group were more at risk of depression (OR=5.38, 95% CI: 1.96-14.78) than those in the higher income group. Similarly, Buddhists and Christians were more likely to be depressed (OR=2.17, 95% CI: 1.02-4.64) than Hindus. Interestingly, participants having more than two children had a higher prevalence of depression (OR=5.14, 95% CI: 1.22-21.63) compared with those having no children. Unmarried participants were more likely to be depressed (OR=4.05, 95%, CI:1.10-14.93) than those who were married. Conclusion: The working Nepali adult male population in Nepal, including returning migrants, is at risk of depression, but this risk is lower in those in the higher income group, returnee migrants, married, Hindus and those with no children. This study highlights the need to monitor and develop national policies to ensure the mental health of Nepali male adult population, including returnee migrants.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.

Caribbean SIDS are among the most vulnerable to climate change which will have a disproportionate impact on local environments and economies. Whilst there is a growing literature on how Caribbean SIDS can adapt to become more resilient a question that has received little attention is with regard to migration as an unplanned response. It is recognised that events such as hurricanes and flooding can lead to internal relocation in the short term but societal responses to droughts through migration have not generally been investigated. This paper seeks to address this by considering the case of the island of Carriacou, part of the state of Grenada. Carriacou with its small population, limited land area and local economy, historically based on agriculture has had a high degree of migration. This is in part a response to limited economic opportunities. Environmental stress manifest through limited water availability, inappropriate land management and social conditions is likely to be exacerbated by climate change and variability. Resultant increases in the frequency and intensity of droughts, in the absence of proactive interventions, are likely to result in non-linear migration, both to Grenada itself and beyond.

Hepatocellular Carcinoma is one of the most predominant malignancies with high fatality rate and is rising at an alarming rate because it is quite resistant to radioand chemotherapy. The proliferation, migration and activation of endothelial cells are involved in tumor occurrence and development. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. In this research, Td-ECs were derived from human umbilical vein endothelial cells (HUVECs) by treating HUVECs with the conditioned medium of human liver cancer cell line HepG2. The effects of indirubin on cell proliferation, migration, invasion and angiogenesis of Td-ECs were assessed. Indirubin significantly inhibited Td-EC cell proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration and angiogenesis. However, indirubin’s effects on HUVECs were weaker than on Td-ECs.

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushroom have been investigated for various allergic diseases. However, antiaging and anti-inflammatory activities of inotodiol under different types of oxidative stress and impact of inotodiol on collagen and hyaluronan synthesis are not sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (the inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulation such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced overexpressions of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role of pure inotodiol/inotodiol concentrate in prevention of skin aging. These results enlighten anti-inflammatory and anti-aging effect of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

The prevailing challenge in our current era is climate change, a crisis recognized by the global community that has prompted immediate actions to confront and mitigate its consequences. There is a consensus among scientists that human activities, driven by developmental ambitions, are the driving force behind the ongoing climate crisis. “The well-documented aftermath, including the rise in sea levels, coastal erosion, reduced agricultural yields, compromised access to clean water, and health implications, emphasizes the intricate and wide-ranging effects of climate change.” Furthermore, there is an increasing recognition that climate change gives rise to distinct social, economic, and divergent consequences. “Although all countries worldwide will undergo the impacts of climate change, the distribution of these effects will differ among regions, generations, age groups, income levels, occupations, and genders.” Notably, the adverse consequences will disproportionately impact the impoverished, predominantly situated in developing nations. “This paper explores the effects of climate change on displacement and the ensuing refugee dilemma.” It aims to scrutinize the inclusion of climate-induced displacement in the present international framework, encompassing both climate change and refugee regimes. The paper promotes a human rights-centred approach to tackling displacement stemming from climate change.

TNF-related apoptosis-inducing ligand (TRAIL or Apo2 or TNFSF10) belongs to the TNF superfamily. When bound to its agonistic receptors, TRAIL can induce apoptosis in tumour cells, while sparing healthy cells. This tumour selectivity prompted, over the last three decades, many studies aiming at evaluating the anti-tumoral potential of TRAIL or its derivatives. Although most of these attempts have failed, so far, novel formulations are still being evaluated. Yet, emerging evidence indicates that TRAIL can also trigger, on the other hand, a non-canonical signal transduction pathway that is likely to be detrimental for its use in oncology. Likewise, increasing studies suggest that TRAIL can induce, through Death receptor 5 (DR5) in some circumstances, tumour cell motility, potentially leading to and contributing to tumour metastasis. While the pro-apoptotic signal transduction machinery of TRAIL is well known from a mechanistic point of view, that of the non-canonical pathway is less understood. We are reviewing here the current state of knowledge of TRAIL non-canonical signalling.

ERK1/2 phosphorylation is frequently downregulated in the early phase of colon tumorigenesis with subsequent activation of ERK5. In the current work, we studied the advantage of ERK1/2 downregulation for tumor growth by dissecting the individual functions of ERK1 and ERK2. The patient sample data demonstrated decreased ERK1/2 phosphorylation in the early phase of tumorigenesis followed by upregulation of the phosphorylation in late-stage colon adenocarcinomas with intratumoral invasion or metastasis. In vitro results indicated SOD3-mediated coordination of small GTPase RAS regulatory genes in the inhibition of RAS-ERK1/2 signaling. In vitro and in vivo studies suggested that ERK2 has a more prominent role in chemotactic invasion, collective migration, and cell proliferation than ERK1. Noteworthily, simultaneous ERK1 and ERK2 expression inhibited collective cell migration and proliferation but tended to promote invasion, therefore suggesting that ERK1 controls ERK2 function. According to the present data, phosphorylated ERK1/2 at the early phase of colon adenocarcinoma limits tumor mass expansion, whereas reactivation of the kinases at the later phase of colon carcinogenesis is associated with the initiation of metastasis. Additionally, our results suggest that ERK1 is a regulatory kinase, which coordinates ERK2-promoted chemotactic invasion, collective migration, and cell proliferation. Our findings indicate that ROS, especially H2O2, are associated with the regulation of ERK1/2 phosphorylation in colon cancer either increasing or decreasing the kinase activity. The data suggesting a growth-promoting role for ERK2 and a regulatory role for ERK1 could result in new avenues in the developmental strategies for cancer therapy.

The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in the human invasion ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly high expression of Nudt2 in the human invasion ductal carcinoma tissues was observed in our study. Knockdown of Nudt2 in TNBC cell lines showed a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest. A significant reduction in the migration and invasion of Nudt2 knockdown TNBC cell lines was also observed. The effect of Nudt2 knockdown in the TNBC cell lines on tumorigenicity and anchorage-independent growth was assessed, where significant reductions in the Nudt2 knockdown TNBC cell lines were found. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

Adolescents often migrate unaccompanied by a caregiver, facing specific risks. Mentoring has been identified as a strategy with positive results for youth at risk. Its application with unaccompanied minors (UM) refugees and asylum seekers has gained momentum within EU countries receiving refugee citizens from the EU relocation program. Portugal hosts the fourth highest number of Middle East and North Africa UM refugees and asylum seekers among EU countries. Thus, it´s relevant to review strategies and intervention programs, focused on mentoring to inform future programs in Portugal supporting UM. This article aims to describe the use of mentoring strategies towards integrating UM refugees, and how this has been taking place in Portugal. This review has the potential to inform professionals, namely social education professionals involved in the Portuguese refugee relocation program and encourage the discussion about creating based mentoring-based programs for this target group.

As a fundamental, overall, and strategic issue facing human society, human migration is a key factor affecting the development of countries and cities given constantly changing population numbers. The fuzziness of the spatiotemporal attributes of human migration limits the pool of open-source data for human migration prediction, leading to a relative lag in human migration prediction algorithm research. This study expands the definition of human migration research, reviews the progress of research into human migration prediction, and classifies and compares human migration algorithms based on open-source data. It also explores the critical uncertainty factors restricting the development of human migration prediction. Given the effect of human migration prediction, in combination with artificial intelligence and big data technology, the paper concludes with specific suggestions and countermeasures aimed at enhancing human migration prediction research results to serve economic and social development and national strategy.

A recent study from our lab revealed that inhibition of cyclooxygenase-2 exclusively reduces the level of PGE2 amongst the prostanoids and hamper the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence the cranial neural crest cell (CNCC) migration were checked in chick embryo after inhibiting the COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1, CDH2, MSX1, and TGF-β, observed in the etoricoxib treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCC. The histological features and levels of FoxD3 as well as PCNA further consolidates the role of COX-2 in migration and survival of CNCC in developing embryo. The results of the current study indicate that the COX-2 plays a pivotal role in orchestrating the proliferation and migration of CNCC during embryonic development of chick.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Monarch butterflies are a species of conservation priority due to declining overwintering populations in both eastern and western North America. Declines in western overwintering monarchs—more than 99% since monitoring began—are especially acute. However, the degree to which the western monarch is a distinct biological entity is uncertain. In this review, we focus on phenotypic and genetic differentiation between eastern and western monarchs, with the goal of informing researchers and policy-makers who are interested in monarch conservation. Eastern and western monarchs occupy distinct environments and show some evidence for phenotypic differentiation—particularly for migration-associated traits—though population genetic and genomic studies suggest that they are genetically indistinguishable from one another. We suggest future studies that could improve our understanding of differences between eastern and western monarchs. We also discuss the concept of adaptive capacity in eastern and western monarchs as well as non-migratory populations outside of the monarch’s primary North American range.

Migrations are much more important than currently recognised, for explaining important patterns observed in the European archaeology record – according to this archaeology led model. At a high level, they explain the introduction of different farming, monument building, the spread of metalworking and patterns of trade and exchange. This paper presents an archaeogenetic model based on a strategic review of the Neolithic and Chalcolithic archaeology of Europe, alongside a review of recently published ancient DNA data. The model is archaeology led. It takes archaeology themes and proposes migratory events to explain them. Ancient DNA data and further archaeology evidence is then used to test these proposed migrations- to reject or refine them. The model introduces a new and more strategic way of looking at archaeological cultures - that updates early 20th century approaches to studying archaeology cultures, and integrates with the detailed ‘post processual’ studies of the late 20th Century. The model consists of seven maps – each showing multiple migration events – with key evidence to support each migration map. It proposes a new category of a ‘Black Sea’ related population that makes a major genetic contribution to the Middle Neolithic of Europe. The proposed migrations provide an explanation for the observed patterns of archaeology, for example: • multiple Neolithic migrations that introduced, farming and metalworking into Europe; • a major ‘Black Sea’ related ‘Middle Neolithic’ migration that carried advanced knowledge of astronomy that can be recognised in a variety of types of monument from the Neolithic through to Bronze Age Europe; and, • migrations of related cultures (‘supercultures’) that explain patterns of trade and exchange in Bronze Age western Europe. The model also provides ancient DNA and archaeology based support for the key aspects of Childe’s ‘dawn of civilisation’ in Europe and Egypt and Gimbutas’ ‘Old Europe’ and “three waves of migration from the Steppe”.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we will discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we will conclude with a review of recent therapeutic approaches.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Acemella oleracea is known as toothache plant belongs to the family of Asteraceae. It is treated as a medicinal remedy like tuberculosis, illness, cough, rheumatism, and illness. This study was concentrated on the antioxidant, cytotoxic, antimicrobial & thrombolytic activities of methanol extract of Acmella oleracea leaves using in vitro model. The antioxidant activity was estimated as trolox equivalent antioxidant capacity utilizing the DPPH and reducing power tests. The plant extract was tested for its cytotoxic action using a brine shrimp lethality bioassay, thrombolytic activity using clot disruption, and antibacterial activity using a disc diffusion assay technique against four distinct gram-positive and gram-negative bacteria. IC₅₀ value of standard ascorbic acid for DPPH was 7.8µg/ml and the IC50 of the methanol extract of Acmella oleracea leaves was 198.34µg/ml that was moderate effect at all compare with ascorbic acid. Thrombolytic assay of Streptokinase as a positive control showed 88.49% where the extract shows 18.69% lytic activity shows the assay. In this study, the sample of LC₅₀ results of cytotoxicity assay was 1.431 µg/mL which can be treated as less activity. Moreover, the extracts showed low to moderate antibacterial activity against both gram-negative and gram-positive bacterial stains (zone of inhibition-10-26 mm). Vibrio Mimicus bacteria stains exhibited the highest level of activity, with a range of 23 for the diameter of the growth inhibition zone. The current review shows leaf extracts of Acmella oleracea may be used as a source of antioxidant and thrombolytic activity, as well as a significant source of antibacterial and anticancer substances. Further research is required to evaluate in-vivo the pharmacological activity of Acmella oleracea leaves in order to identify the essential metabolites and potential mechanisms.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

The use of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera leaves extract and metallic bismuth, our study aimed at synthesizing bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves as a means of green synthesis that yields nontoxic products and reduces the production of wasteful material. To this end, the M. oleifera leaves extract was treated with a bismuth nitrate pentahydrate solution. A color change from light brown to dark brown indicates the synthesis of bismuth nanoparticles. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. Antioxidant property of MO synthesised bismuth Nanoparticles was evaluated and in line with the extract used in the synthesis of NPs. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized bismuth nanoparticles have a size in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, similarly to the inhibition exerted by Moringa extract, especially against Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, the hydroalcoholic extract of M. oleifera leaves was successfully used in the synthesis of bismuth nanoparticles, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.

The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

The Eastern Himalayan Syntaxis (EHS), featured by an exceptionally intense compression orogeny and an extremely rapid surface erosion rate, stands out as a prime area for investigating surface processes and landscape evolution. Understanding the formation of the EHS holds significant importance in advancing our comprehension of the evolutionary dynamics within the Tibetan Plateau and the complex interplay between endogenic and exogenic geological processes. Currently, two models, namely the tectonic aneurysm and the syntaxis expansion model, have been proposed to explain the formation and evolution of this syntaxis. In this study, we employ a multi-disciplinary approach, integrating geomorphic indices such as slope, relief, Hypsometric Integral (HI), Normalized Channel Steepness (Ksn), River Slope-Basin Area Integration (χ), combined with erosion rates on long-medium-short term timescales obtained from thermochronology, cosmogenic nuclides 10Be and landslide disaster probability data. Our findings suggest a relatively high tectonic activity in the confluence of the Yigong and Parlung Rivers in the northern end of the syntaxis. Moreover, our data reveals that spatial variability of tectonic activity is the primary driver of regional geomorphologic features and the spatial-temporal characteristics of erosion observed in the EHS, with lithology and climatic precipitation playing a lesser role. Furthermore, the northwards migration of the EHS appears to elucidate the shift of tectonic activity and rapid erosion from the core of the syntaxis near the Namche Barwa towards the confluence of the Yigong and Parlung Rivers. This northwards migration of the EHS underscores the need for increased attention to the high geological hazard risk in the northern part of the EHS.

In preserving genetic diversity among domestic animal breeds, the strategies emphasizing be-tween-breed diversity may be not optimal by neglecting within-breed variation. The present study aimed to assess the extent of the population subdivision of Mangalica pigs and the contri-bution of migration intensity to their substructure. Genealogy analysis was performed for breeding animals born between 1981 and 2023 examining three colour variations (Blonde, Swal-low-Belly, and Red). The fixation index (FST) was calculated and evaluated by Multidimensional Scaling and Clustering to expose the population substructure. The average FST is 0.04 for the Blonde and 0.05 for the Swallow-Belly and the Red while in the active herds, these parameters are smaller being 0.03 and 0.04, respectively. The migration of individuals affected 61.63% of the Blonde, 75.53% of the Swallow-Belly, and 63.64% of the Red breed herds. No population sub-structure was found in any Mangalica breed which can be explained by the extensive within breed migration among the herds.

Globally, large numbers of adults remain unbanked and most of them live in rural areas of the Third World. The recent outbreak of the COVID-19 pandemic has shown us how inequalities in accessing financial services continue to affect us. However, financial inclusion has emerged as an effective tool to tackle socioeconomic ills and drive economic development. In fact, due to these modern technological developments, the number of studies in this area is very limited, especially in the context of developing economies. This study examines the impacts of migrant remittances on digital financial inclusion within households using the Migration and Remittance Household Survey in Bangladesh. To meet the research objectives of this study, a household survey was conducted and interviewed 2,165 households in 2022-2023 in Bangladesh. This study finds that the coefficient of remittance has a positive relationship with the probability of using mobile banking for a household's financial transactions. However, the use of ATM cards by households for financial transactions has not been significantly affected. The article concludes that remittance flows may enhance access to and use of digital financial inclusion by reducing some of the barriers and costs in Bangladesh, which can greatly contribute to the country's economic growth by creating and increasing a strong fund for investment.

CD4+ T cells orchestrate and regulate immunity within jawed vertebrates, yet our understanding of their evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and highresolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi omics data which can be used as a reference atlas to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.

For deep-penetrating geochemistry, there is a frontier issue as to how to explore ore-bearing information deep in covered areas, while it is, too, important to investigate the geochemical migration of ore-forming elements for the development of exploration geochemistry. In this study, a 380-day migration column experiment was conducted with surface soil and pure Cu powder collected from the Yujiashan study area in Wuhan City, Hubei Province taken as the object of research to simulate the migration process of ore-forming elements under natural conditions. The results showed obvious vertical migration of the ore-forming elements and conversion of mobile metal forms in the process; further, according to 6 groups of simulation experiments that took 45 days to conduct on migration column samples and the surface oil and Cu powder collected from the Pulang mining area in Yunnan Province, the vertical migration of the ore-forming element was still visible, and the exogenous substance (pure Cu powder) could enhance the anomaly without changing the basic migration mechanism. This indicates that Cu might migrate in a stable manner in soil cover in the Pulang mining area, and its migration was mostly driven by the transformation of Fe-Mn oxide bound state and organic bound state; finally, a multifractal analysis was conducted, revealing that the ore-forming elements presented a nonlinear and complex structure during their upward migration, which caused anomalies in the covered area, and multiple parameters exerted a certain indicative effect on different source intensities and properties of soil. In this study, laboratory simulations were performed to summarize the active-state evolution pattern and migration mechanism of ore-forming elements with a view to providing technical support and theoretical guidance for geochemical prospecting in the covered region.

The development of mineral deposits causes changes that are comparable to natural exogenous geological processes, and in local areas of intensive mining activity prevail over them. In this article, a diamond deposit is selected, developed by quarries of great depth, and a forecast is made of the impact of drainage water discharge on changes in the composition of surface water and bottom sediments during the entire period of development of the deposit. Modeling was per-formed according to various scenarios, taking into account changes in the total dissolved solids of groundwater from 0.5 to 21.7 g/kg H2O. Thermodynamic calculations were carried out using the HCh software package. The role of dissolved organic carbon in the migration of chemical elements and the effect of DOC on the precipitation of chemical elements from mixing solutions is given. It has been established that fulvic acid completely binds to Fe in the Fe(OH)2FA– complex in all types of natural waters and under all mixing scenarios. With humic acid, such a sharp competitive complex formation does not occur. It is distributed among the various elements more evenly. It was determined that the mass of precipitating iron in the presence of DOC decreases by 18-27%, and its precipitation in winter is more intense. In contrast to Fe, precipitation of Ca, Mg, and C from solution with DOC is higher in summer, and there are more of them in solution in winter. This study contributed to a better understanding of the behavior of heavy metals in surface waters and sediments under anthropogenic pressures in order to improve the sustainable management of water resources in the face of anthropogenic activities.

Our understanding of how microbiome signatures are modulated in wild fish populations remains poorly known and has, until now, mostly been inferred from studies in commercial and farmed fish populations. Here, we have studied for the first time changes in the skin and blood microbiomes of the Salmo trutta population of the volcanic Kerguelen archipelago located at the northern limit of the Antarctic Ocean. Kerguelen is a natural framework of population expansion and a likely situation under further climate change in distribution areas. Our results showed that S. trutta of Kerguelen has a microbiome signature distinct from those of salmonids of the Northern Hemisphere. Our study also revealed that the skin and blood microbiomes differ between sedentary and migratory S. trutta. While 18 phyla were shared between both groups of trout, independent of the compartment, six phyla were unique to migratory trout. Further analyses showed that microbiome signatures undergo significant site-specific variations that correlate, in some cases, to the peculiarity of specific ecosystems. Our study also revealed the presence of potential pathogens at particular sites and the impact of abiotic factors on the microbiome, most notably due to the volcanic nature of the environment. This study contributes to a better understanding of the factors that modulate the microbiome signatures of migratory and sedentary fish populations. It will also help better monitor climate change's impacts on the colonization process in the sub-Antarctic region.

Urbanization is a global phenomenon and as the economies are shifting from rural based subsistence to services based, the net flow of migration is inevitable. Unfortunately, In India, migration is very poorly understood. India is next to China in production of bricks, accounting for nearly 13% of global annual bricks’ production. The condition of brick-kiln workers is pitiable, especially due to poor care available. They are exposed to health hazards such as various communicable diseases, sexually transmitted diseases and occupational health hazards. The diseases such as respiratory problems, allergies, gastrointestinal ailments and malnutrition are frequent in these populations. This paper reflects upon various policies that exist for the welfare of unorganised sector but do these workers qualify for these benefits? This paper provides empirical basis for paradigm shift for policy formulation to provide safety nets for migrant population and have better urban planning for future.

International migration is closely tied to demographic, socioeconomic, and environmental factors and their interaction with migration policies. Using a combination of a gravity econometric model and an overlapping generations model, we estimate the probability of bilateral migration among 160 countries in the period of 1960 to 2000 and use these findings to project international migration flows and their implication for income inequality within and between countries in the 21st century under five shared socioeconomic pathways (SSPs). Our results show that international migration not only increases the welfare in developing countries, but also closes the inequality gap within and between low-skilled and high-skilled labor in these countries. In most developed countries on the contrary, international migration increases the inequality gap and slightly reduces output. These changes are not uniform and vary significantly across countries depending on their population growth and human capital development trajectories. Overall, while migration is strongly affected by inequality between developed and developing countries, it has an ambiguous impact on inequality within and between countries.

Fluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimal distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.

The worldwide number of migrants has had a rapid increase during the last fifteen years. Despite the extensive research studies that elucidate the increase in migrants' recipient countries, we know little about the relationship between the climate factors and human mobility in the countries of origin. Hence, this study focuses on the effects of weather and the propensity of individuals to leave a territory by measuring the importance of rain precipitation or the lack of it in one of the critical food corridors of Central America, formed by El Salvador, Honduras, and Guatemala. To study the mobility process, we develop a stochastic frontier model; the main result shows a greater propensity to migrate when there is a significant drought event in the place of origin. Some other factors that motivate people to leave their homeland are the effect of other climate events measured through the control system (ENSO), homicide levels, economic performance, and exchange rate. The findings allow differentiating between drought and excess precipitation on a population and mobility to other territories. In addition, these results permit us to derive observable implications of the different effects of flooding and drought and create public policies of prevention, mitigation, and resilience.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

The intracellular calcium concentration ([Ca2+]i) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in tumor initiation and progression. Here we show that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced SOCE through TRPC6 activation that associated reduced cells malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments, revealed that the ppFurin-expressing cells are unable to process adequately the PC substrates proVEGF-C and proIGF-1R. Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231 significantly induces Ca2+ entry which is impaired by silencing of TRPC6 expression. Analysis of TRPC6 activation revealed its up-regulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. The expression of ppFurin in MDA-MB-231 cells reduced their viability and ability to migrate and enhanced their sensitization to the apoptosis inducer hydrogen peroxide. These findings suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization leading to breast cancer cells malignant phenotype repression and reduction of their resistance to treatments.

Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate if Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signaling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μM at 72 hours, and that 5 μM CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

Objectives: Female genital mutilation (FGM) is a significant public health problem. It is estimated around 14,700 women affected by FGM live in Switzerland, primarily among women with a history of migration. Our qualitative research investigated the sexual health of immigrant women living with FGM in Switzerland, describing their own perception of health, reproductive life and sexuality. Methods: We conducted semi-structured, in-depth interviews with a group of eight immigrant women of African origin living in Switzerland with Type III FGM (infibulation). Results: Seven of the women were from Somalia and one from Ivory Coast. All of the Somali women were mothers and married (two separated), and the Ivorian woman was a single mother. The women in our study reported a low level of sexual satisfaction and reproductive health. They affirmed their desire to improve, or at least change, their condition. Although they rarely talk with their husbands about sexual subject matter, they would like to include them more and improve dialogue. Conclusions: Specific socio-sexual management is recommended when caring for immigrant women living with FGM in order to respond to their specific health care needs. Multidisciplinary approaches may be able to offer more comprehensive health care, including facilitated communication to improve dialogue between women and health care professionals, and eventually between women and their husbands in discussing sexual matter.

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

Hydrogenated water has emerged as a novel approach in the field of health and wellness. It is be-lieved to have potent antioxidant properties that can neutralize harmful free radicals in the hu-man body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic re-view to evaluate the potential benefits of hydrogenated water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded inves-tigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogenated water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigor-ous methodologies is needed to substantiate these findings. Current research needs to fully ex-plain the mechanisms behind the potential benefits of hydrogenated water. Continued scientific exploration will provide valuable insights into the potential of hydrogenated water as an adjunc-tive therapeutic approach in the future.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

Quinoa, known as the "golden grain" for its high nutritional value, is a significant source of essential nutrients, including proteins, minerals, vitamins, polyphenols, phytosterols, and flavonoids. However, the biological functions of quinoa polysaccharides remain understudied. In this research, two crude quinoa polysaccharides extracts (Q-40 and Q-60) were obtained extracting by 40% and 60% alcohol. The purity of Q-40 and Q-60 was 58.29% and 62.15%, with protein contents of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47484 to 626488 Da, while Q-60 showed a range of 10025 to 47990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of Methicillin-resistant Staphylococcus aureus (MRSA) and E. coli, while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in application of quinoa in food and functional food industries.

Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.

Mass transfer and phase transition have important effect on the velocity of bubble migration in deepwater wellbore, and accurate prediction of bubble migration velocity is crucial for calculating the safe shut-in period of deepwater oil and gas well. Therefore, the effect of bubble dissolution mass transfer and hydrate phase transition on bubble migration behavior in deepwater environment have attracted extensive attention from researchers in the fields of energy, marine chemistry, and marine engineering safety. In this work, a new model of bubble migration velocity in deepwater is developed, which considers the effect of hydrate phase transition and gas-water bidirectional cross-shell mass transfer during bubble migration. Based on the observation data of bubble migration in deepwater, the reliability of the model in predicting bubble migration velocity is verified. Then, the model is used to calculate and analyze the bubble migration velocity and bubble migration cycle under different initial bubble size, different annular fluid viscosity and density. The results show that the initial size of bubble and the viscosity of annulus fluid are the main factors affecting the migration velocity of bubble, but the density of annulus fluid has little effect on the migration velocity of hydrated bubble and clean bubble. In addition, the migration velocity of clean bubble gradually increases during the migration process from the bottom to the wellhead, while the migration velocity of hydrated bubble is divided into gradually decreasing stage and slowly increasing stage. The gas consumption and the thickening of hydrate shell in the gradually decreasing stage play a dominant role, and the increase of bubble volume caused by the decrease of pressure in the slowly increasing stage is the most important factor. The formation of hydrated bubble can significantly reduce the migration velocity of bubble and effectively prolong the safe shut-in period. This study provides a reference for quantitative description and characterization of complex bubble migration behavior with phase change and mass transfer in deepwater environment.

A large number of studies have concluded that since housing pressure will affect the mobility of highly skilled young migrants (HSYM) in Chinese cities and regions, it is necessary to apply corresponding housing policies to adjust housing unaffordability for HYSM. This study uses a survey data conducted in China's Zhejiang Province of China, where specific policies have been implemented to attract talent and found that housing does crowds out the HSYM from a city, but the HSYM who have a master's degree or above or who work in government organizations or state-owned enterprises are more tolerant of housing unaffordability. The unmarried or those staying in the city for a long period are less tolerant of housing unaffordability. Meanwhile, there are the heterogeneous impacts of factors on the HSYM's tolerance for housing unaffordability across cities of different levels. Therefore, housing policies should highlight urban differences and intra-group differences.

This paper draws on data from a representative city-wide household food security survey of Nairobi conducted in 2017 to examine the importance of food remitting to households in contemporary Nairobi. The next section of the paper provides an overview of urbanization and the rapid growth of Nairobi which has led to growing socio-economic inequality, precarious livelihoods for the majority, and growing food insecurity, as context for the more detailed empirical analysis of food security and food remittances that follows. It is followed by a description of the survey methodology and sections analyzing the differences between migrant and non-migrant households in Nairobi. Attention then turns to the phenomenon of food remitting, showing that over 50% of surveyed households in the city had received food remittances in the previous year. The paper then uses multivariate logistic regression to identify the relationship between Nairobi household characteristics and the probability of receiving food remittances from rural areas. The findings suggest that there are exceptions to the standard migration and poverty-driven explanatory model of the drivers of rural-urban food remitting and that greater attention should be paid to other motivations for maintaining rural-urban connectivity in Africa.

Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate neuroinflammatory response of microglia remain largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on immortalized human microglial cells. We found that EVs induced a rapid increase in intracellular Ca2+ and promoted a significant ATP release in microglial after 20 min of treatment. Boyden chamber assays revealed that EVs promoted microglial migration by 20 %. Pharmacological inhibition of different subtypes of purinergic receptors demonstrated that EVs activated microglial migration preferentially through the P2X4R pathway. Proximity ligation and co-immunoprecipitation assays revealed that EVs promote association between milk fat globule-epidermal growth factor-factor VIII (MFG-E8) and P2X4 receptor proteins. Furthermore, pharmacological inhibition of αVβ3/αVβ5 integrin suppressed EV -induced cell migration and formation of lipid rafts in microglia. These results demonstrate that EVs promote microglial motility through P2X4 R/ MFG-E8 – dependent mechanisms. Our findings provide novel insights into the molecular mechanisms through which EVs target human microglia that may be exploited for the development of new therapeutic strategies targeting disease associated neuroinflammation.

The Evolutionary history and domestication of Camels are largely unexplored because of the lack of well dated early archaeological records. However, limited records suggest that domestication of Camels likely happened in the late second millennium BCE. Over the time, camels have helped human for their basic needs like meat, milk, wool, dung to long routes transportation. This multifaceted animal has helped the mankind to connect through continents and in trade majorly through the Silk route. In India, both dromedary and Bactrian camels are found and their habitat is entirely different from each other, dromedaries inhabit in hot deserts and Bactrians are found mostly in cold places (Nubra Valley, Ladakh). Fewer studies on Indian dromedaries have been conducted but no such studies are done on Bactrian camels. It is needed to study the genetics of Bactrian camels to find out their genetic affinity and evolutionary history with other Bactrians found in different parts of the world. Furthermore, parallel studies on humans and Bactrian camel are required to understand the co-evolution and migration pattern of humans during their dispersal in different time periods.

The assessment of caprock integrity for underground storage of CO2 and/or enhanced oil recovery (EOR) systems is a multiscale endeavor. Caprock sealing behavior depends on coupled processes that operate over a broad range of length and time scales including nanoscale heterogeneity in capillary and wettability properties to depositional heterogeneity that is basin wide. Larger-scale sedimentary architecture, fractures, and faults can govern properties of potential “seal-bypass” systems that may be difficult to assess. We present a multiscale investigation of geologic sealing integrity of the caprock system that overlies the Morrow B sandstone reservoir, Farnsworth Unit, Texas, USA. The Morrow B sandstone is the target geologic unit for an on-going combined CO2 storage–EOR project by the Southwest Regional Partnership on Carbon Sequestration (SWP). Methods and/or data encompass small-to-large scales, including: petrography using electron and optical microscopy; mercury porosimetry; core examinations of sedimentary architecture and fractures; well logs; a suite of geomechanical testing; and a noble gas profile through sealing lithologies into the reservoir, as preserved from fresh core. The combined data set allows a comprehensive examination of sealing quality by scale, by primary features that control sealing behavior, and an assessment of sealing behavior over geologic time.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

: Annona squamosa L. is an important medicinal plant used in traditional medicine for the treatment of various diseases. Different parts of A. squamosa L. have various therapeutic effects; however, the anticancer activity of the leaves has not yet been identified. In vitro, MTT, nuclear staining, and LDH assays were used to evaluate cell survival and proliferation in cells exposed to the extracts. The effect of the extracts on cell migration was investigated using a monolayer wound repair assay, and the apoptotic effects were evaluated using flow cytometry. A breast cancer model was used to study the effect of the extract on the tumor size, and the expression of different proliferative and apoptotic markers was evaluated by immunohistochemical analysis. At a concentration of 100 µg/mL, A. squamosa leaf extracts exerted strong antiproliferative and cytotoxic effects against various cell lines. The extracts reduced wound closure and strongly induced apoptosis. In vivo study, rats were sacrificed 24 h after the last injection, and tumor size, as well as the expression of proliferative and apoptotic markers, were observed to be greatly affected by treatment with the extracts. Therefore, A. squamosa leaf extract may be developed as a potential novel drug to treat breast cancer in the future

Anthropogenic change is associated with population growth, land use change, and changing economies. However, internal migration patterns and armed conflicts are also key drivers behind anthropogenic and demographic processes. To better understand this sort of change, we explore the spatial relationship between forced migration due to armed conflict and changing demographic factors in Colombia, a country which has a recent history of 7 million internal migrants. In addition, we use remote sensing, Google Earth Engine, as well as spatial statistical analyses of demographic data in order to measure anthropogenic change between 1984 and 2008; and we look into spatiotemporal relationships between both demographic and anthropogenic changes, which are caused by forced migration. We find, thus, that the latter is significantly and positively related to an increasing rural-urban kind of migration which originates in armed conflict, and results show that it is also negatively associated with interregional expulsion. Indeed, anthropogenic prints (term hereafter used to denote changes in nighttime satellite imagery) pertaining to different regions have had different sensitivities towards forced migration, and across different time periods. Finally we discuss how social and political phenomena such as Colombia’s armed conflict can have significant effects on the dynamics and motions of humans and territories in countries of the Global South.

Angiogenesis, the sprout and growth of new blood vessels from existing vasculature, is an important process of tumor development for the supply of oxygen and nutrition to cancer cells. Endothelial cell is a critical player in angiogenic process by modulating cell proliferation, cell motility, and cell morphology in the response to pro-angiogenic factors and environments provided by tumor and cancer cells. Recent in vivo and in vitro studies have revealed that gap junction of endothelial cells also participates in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexins expression in endothelial cells, whereas endothelial connexins involve in angiogenic tube formation and cell migration of endothelial cells via both gap junction channel function dependent or independent mechanisms. In particular, connexin might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during angiogenic processes. Here, we review the implication for endothelial gap junction and cellular mechanics in vascular angiogenesis.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

The goal of this study was to develop a rapid diagnostic kit for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HC). Observer scores and absolute signal intensities from the VFA were validated by ELISA. The rapid ten minute point of care VFA test engineered demonstrated a limit of detection of 0.5 IU/ml for ANA and αDNA autoantibodies in human plasma with inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in 22 SLE and 18 HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and 84% accuracy in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease and rapid turnaround, it can also be used to assess SLE prevalence estimates.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, to prevent NMOSD relapses, is common in Sweden, but the knowledge on long-term efficacy and risk for severe infections are limited. We performed a retrospective cohort study with medical chart review of rituximab-treated NMOSD patients at the Karolinska University Hospital, Sweden, to assess the occurrence of relapses and severe infectious events (SIE). Furthermore, we collected data on CD19+ lymphocyte, and IgG levels during therapy. A total of 42 NMOSD patients; 24 with aquaporin -4 antibodies (AQP4+), eight with myelin oligodendrocyte glycoprotein antibodies (MOG+) and 10 with absence of antibodies (double-seronegative) were included. During a mean treatment time of 4.4 years, 37% AQP4+, 75% MOG+, and 60% double-seronegative patients experienced 1 relapse. SIEs were common with 46% of AQP4+, 25% of MOG+, and 40% of double-seronegative patients affected. Incomplete CD19+ lymphocyte suppression did not predict a relapse and there was no correlation between IgG levels and SIEs. In conclusion, our data demonstrated a high risk for both relapses and SIEs in rituximab-treated NMOSD patients highlighting the need for close clinical vigilance of disease activity and infections during treatment.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

: Since the COVID-19 pandemic, people have become aware that materials (products) can transmit infection and have begun to focus on questions such as how bacteria and germs, the sources of in-fection, maintain their infectivity on material surfaces, and the extent to which materials can or cannot prevent this. and to what extent materials can and cannot prevent it. The SIAA, a non-profit organization of many Japanese companies, had created an entirely separate interna-tional standard for materials' antibacterial, antiviral, and antibiofilm properties (products). The authors have studied the academic basis for the operation of the standards and were deeply in-volved as researchers in establishing one of the standards. This paper describes the interna-tional standards and some representative examples of the authors' actual use of these standards and explains the current status and future problems.

Abstract: In the last decade, gypsogenin has widely grabbed the attention of medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin proved itself as a new an-ti-proliferative player battling for a front position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospect rational design. The present article opens a new venue for better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMRspectroscopy and spectroscopy methods were used to characterize the structural properties of newly synthesized derivatives. In order to observe the attributes of drug-like candidates of these derivatives, the number of their molecular properties was estimated. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Findings suggested that Compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8and G10 showed lower binding affinity than Indomethacin when docking performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities were performed for synthesized compounds. Compounds 10 and 11 exhibited significant COX-1 and COX- enzyme inhibitory action with IC50 values of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. The highest analgesic action was exhibited by derivative G11and the compound G10 showed the highest anti-inflammatory response.

Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of polyacetylene-rich vegetables with reduced risk of inflammation and cancer. Polyacetylene supplementation can influence cell growth, gene expression, and immunological responses, and reduce tumour number in rat and mouse models. Cancer chemoprevention by dietary polyacetylenes involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, UPR pathway, growth factor signalling, cell cycle progression, and apoptosis. This review summarises the published research on falcarinol-type polyacetylene compounds and their mechanisms of action regarding cancer chemoprevention and treatment, and also identifies some gaps in our current understanding of the health benefits of these polyacetylenes.

Members of the SOX (SRY-related HMG-box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular models. By providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.