Seasonal biology: Tanycytes give the hypothalamus a spring makeover.

In many species, metabolic and reproductive functions are coupled to the seasons. Tanycytes, specialized glial cells in the hypothalamus, play an important function in these physiological changes. A new study now shows that light exposure drastically alters the formation of sensory cilia on tanycytes.

In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer's Disease and Aging through Redox Biology.

Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-ß- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

Nesting biology and nest structure of the exotic bee Megachile sculpturalis.

From the 1990s, the Southeast Asia native giant resin bee Megachile sculpturalis (Smith, 1853) was introduced first to North America, and then to many countries in Europe. Despite increasing studies on its invasive potential and geographical expansion, information on nesting behaviour of this species is still extremely scarce. To increase knowledge on the nesting biology of M. sculpturalis, we studied multiple aspects of nesting and pollen provisioning in three consecutive years in artificial nests in Bologna, Italy. We observed 166 bees visiting nests, and followed individual nesting behaviour and success of 41 adult females. We measured cavity diameter in 552 nests and characterised the structure in 100 of them. More than 95% of nest diameters ranged between 0.6 and 1.2 cm, overlapping with several sympatric species of cavity-nesting hymenopterans in the study area. Most nests had a first chamber from the entrance of variable length without brood, followed by an average of about two brood cells with a mean length of 2.85 ± 0.13 cm each. The pollen stored in brood cells was almost monofloral, belonging to the ornamental plant Styphnolobium japonicum (L.) Schott. We estimated that a single female should visit ≈180 flowers to collect enough pollen for a single brood cell. These results fill knowledge gaps on the nesting biology and nest structure of the exotic M. sculpturalis, and they are discussed in relation to possible competition with native bees for nesting sites and foraging resources.

Bone health: biology and nutrition.

PURPOSE OF REVIEW: Recent findings in the influence of dietary patterns, dairy products, beverages and microbiota composition and function on bone health are reviewed and discussed. RECENT FINDINGS: Evidence is accumulating on the increased risk of fracture in individuals following a vegan diet. Meta-analysis of randomized controlled trials indicates a favourable, though of low amplitude, effect of dairy products on bone mass accrual during childhood and adolescence. Though mostly based on results from observational studies, it seems that dairy product consumption, particularly fermented dairy products, is associated with a lower risk of hip fracture. Regular green tea drinkers may have a lower fracture risk than tea abstainers. Magnesium intake is beneficial for bone health. Prune supplements prevents bone loss in untreated postmenopausal women. This seems to be associated with modification of gut microbiota. SUMMARY: This information should help the medical practitioners facing questions from their patients on how to protect bone health through nutrition.

The Systematics, Reproductive Biology, Biochemistry, and Breeding of Sea Buckthorn-A Review.

Both the fruit flesh and seeds of sea buckthorn have multiple uses for medicinal and culinary purposes, including the valuable market for supplementary health foods. Bioactive compounds, such as essential amino acids, vitamins B, C, and E, carotenoids, polyphenols, ursolic acid, unsaturated fatty acids, and other active substances, are now being analyzed in detail for their medicinal properties. Domestication with commercial orchards and processing plants is undertaken in many countries, but there is a large need for improved plant material with high yield, tolerance to environmental stress, diseases, and pests, suitability for efficient harvesting methods, and high contents of compounds that have medicinal and/or culinary values. Applied breeding is based mainly on directed crosses between different subspecies of Hippophae rhamnoides. DNA markers have been applied to analyses of systematics and population genetics as well as for the discrimination of cultivars, but very few DNA markers have as yet been developed for use in selection and breeding. Several key genes in important metabolic pathways have, however, been identified, and four genomes have recently been sequenced.

Capsaicinoids and Their Effects on Cancer: The "Double-Edged Sword" Postulate from the Molecular Scale.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.

The complementary roles of STAT3 and STAT1 in cancer biology: insights into tumor pathogenesis and therapeutic strategies.

STATs are a family of transcription factors that regulate many critical cellular processes such as proliferation, apoptosis, and differentiation. Dysregulation of STATs is frequently observed in tumors and can directly drive cancer pathogenesis. STAT1 and STAT3 are generally viewed as mediating opposite roles in cancer development, with STAT1 suppressing tumorigenesis and STAT3 promoting oncogenesis. In this review, we investigate the specific roles of STAT1 and STAT3 in normal physiology and cancer biology, explore their interactions with each other, and offer insights into therapeutic strategies through modulating their transcriptional activity.

Biology of Anemia: A Public Health Perspective.

Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron deficiency (ID), lack of other micronutrients, infection, inflammation, and genetic conditions. ID develops if the iron circulating in the blood cannot provide the amounts required for red blood cell production and tissue needs. ID anemia develops as iron-limited red blood cell production fails to maintain the hemoglobin concentration above the threshold used to define anemia. Globally, absolute ID (absent or reduced body iron stores that do not meet the need for iron of an individual but may respond to iron supplementation) contributes to only a limited proportion of anemia. Functional ID (adequate or increased iron stores that cannot meet the need for iron because of the effects of infection or inflammation and does not respond to iron supplementation) is frequently responsible for anemia in low- and middle-income countries. Absolute and functional ID may coexist. We highlight continued improvement in understanding the roles of infections and inflammation in causing a large proportion of anemia. Deficiencies of nutrients other than iron are less common but important in some settings. The importance of genetic conditions as causes of anemia depends upon the specific inherited red blood cell abnormalities and their prevalence in the settings examined. From a public health perspective, each setting has a distinctive composition of components underlying the common causes of anemia. We emphasize the coincidence between regions with a high prevalence of anemia attributed to ID (both absolute and functional), those with endemic infections, and those with widespread genetic conditions affecting red blood cells, especially in sub-Saharan Africa and regions in Asia and Oceania.

System biology analysis to develop diagnostic biomarkers, monitoring pathological indexes, and novel therapeutic approaches for immune targeting based on maggot bioactive compounds and polyphenolic cocktails in mice with gastric cancer.

Early diagnosis and prognosis are prerequisites for mitigating mortality in gastric cancer (GaCa). Identifying some causative or sensitive elements (coding RNA (cRNA)-non-cRNAs (ncRNAs)) can be very helpful in the early diagnosis of GaCa. Notably, despite significant development in the GaCa treatment, the outcome of patients does not remain satisfactory due to limitations such as multi-drug resistance and tumor relapse. Therefore, more attention has been drawn to complementary therapies and the use of supplements. In this regard, Polyphenol natural compounds (PNC) and maggot larvae (MaLa) alone or in combination were administered along with chemotherapy (paclitaxel) to N-methyl-N-nitrosourea (MNU)- induced murine tumor model. In addition, in order to identify potential diagnostic or prognostic biomarkers, transcriptomics analysis was performed through a bioinformatics approach. Then transcription profile of ncRNAs with their target hub genes was assessed through qPCR Real-Time, Western blot, and ELISA. According to the bioinformatics results, 17 hub genes (e.g., IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1ß, SPP1, LOX, COL1A1, and IFN-γ) were explored that contribute towards inflammation and oxidative stress and ultimately GaCa development. Upstream of the mentioned hub genes, regulatory factors (lncRNA XIST and NEAT1) were also identified and introduced as prognosis and diagnosis biomarkers for GaCa. Our results showed that PNC alone and in combination with MaLa was able to reduce the size and number of tumors, which is related to the reduction of genes expression levels (including IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1ß, SPP1, LOX, COL1A1, IFN-γ, NEAT1, and XIST). In conclusion, PNC and MaLa have the potential to be considered as complementary and improving chemotherapy due to their effective compounds. Also, the introduced hub gene and lncRNA in addition to diagnostic and prognostic biomarkers can be used as druggable proteins for novel therapeutic targeting of GaCa.

Investigation of the therapeutic role of native plant compounds against colorectal cancer based on system biology and virtual screening.

This study investigated the anticancer effects of compounds extracted from native plants on colon cancer following drug-target-network analysis and molecular docking. Based on the ChEBI database, compounds were identified in medicinal plants and weeds in the Chaharmahal and Bakhtiari provinces of Iran. A drug-target network was constructed based on candidate colon cancer protein targets and selective compounds. Network pharmacology analysis was conducted against the identified compounds and subjected to molecular docking studies. Based on molecular dynamics simulations, the most efficient compounds were evaluated for their anticancer effects. Our study suggests that TREM1, MAPK1, MAPK8, CTSB, MIF, and DPP4 proteins may be targeted by compounds in medicinal plants for their anti-cancer effects. Multiorthoquinone, Liquiritin, Isoliquiritin, Hispaglabridin A, Gibberellin A98, Cyclomulberrin, Cyclomorusin A, and Cudraflavone B are effective anticancer compounds found in targeted medicinal plants and play an important role in the regulation of important pathways in colon cancer. Compounds that inhibit MIF, CTSB, and MAPK8-16 appear to be more effective. Additional in vitro and in vivo experiments will be helpful in validating and optimizing the findings of this study.

Mega-scale experimental analysis of protein folding stability in biology and design.

Advances in DNA sequencing and machine learning are providing insights into protein sequences and structures on an enormous scale1. However, the energetics driving folding are invisible in these structures and remain largely unknown2. The hidden thermodynamics of folding can drive disease3,4, shape protein evolution5-7 and guide protein engineering8-10, and new approaches are needed to reveal these thermodynamics for every sequence and structure. Here we present cDNA display proteolysis, a method for measuring thermodynamic folding stability for up to 900,000 protein domains in a one-week experiment. From 1.8 million measurements in total, we curated a set of around 776,000 high-quality folding stabilities covering all single amino acid variants and selected double mutants of 331 natural and 148 de novo designed protein domains 40-72 amino acids in length. Using this extensive dataset, we quantified (1) environmental factors influencing amino acid fitness, (2) thermodynamic couplings (including unexpected interactions) between protein sites, and (3) the global divergence between evolutionary amino acid usage and protein folding stability. We also examined how our approach could identify stability determinants in designed proteins and evaluate design methods. The cDNA display proteolysis method is fast, accurate and uniquely scalable, and promises to reveal the quantitative rules for how amino acid sequences encode folding stability.

Hormonal biomarkers provide insights into the reproductive biology and pollutants-associated health hazards of endangered dolphins.

Contaminants are known to contribute to the reproductive health hazards of wildlife, but pollutants-associated detrimental impacts on the endangered Indo-Pacific humpback dolphins (Sousa chinensis, IPHD) are largely unknown due to a lack of reproductive parameters. Here we validated and applied blubber progesterone and testosterone as reproductive biomarkers to assess reproductive parameters of IPHD (n = 72). The gender-specific progesterone concentrations and progesterone/testosterone (P/T) supported progesterone and testosterone as valid biomarkers in identifying the genders of IPHD. Significant month-to-month variations of two hormones indicated a seasonal reproduction, in accordance with the observation of photo-identification approach, further supporting testosterone and progesterone as ideal reproductive biomarkers. Progesterone and testosterone concentrations showed significant differences between Lingding Bay and West-four region, possibly due to chronically geographic-specific pollutants differences. The significant relationships between sex hormones and multiple contaminants suggested that contaminants contribute to the disruption of testosterone and progesterone homeostasis. The best explanatory models between pollutants and hormones suggested that dichlorodiphenyltrichloroethanes (DDTs), lead (Pb) and selenium (Se) were the major risk factors jeopardizing the reproductive health of IPHD. This is the first study on the relationship between pollutant exposure and reproductive hormones in IPHD and represents a substantial advance in understanding the detrimental reproductive impacts of pollutants on endangered cetaceans.

Effects of source of supplementary trace minerals in pre- and postpartum diets on reproductive biology and performance in dairy cows.

Our objectives were to evaluate the effects of complete replacement of inorganic salts of trace minerals (STM) with organic trace minerals (OTM) in both pre- and postpartum diets on ovarian dynamics, estrous behavior measured by sensors, preimplantation conceptus development, and reproductive performance in dairy cows. Pregnant cows and heifers (n = 273) were blocked by parity and body condition score and randomly assigned to either STM or OTM diets at 45 ± 3 d before their expected calving. Pre- and postpartum diets were formulated to meet 100% of recommended levels of each trace mineral in both treatments, taking into consideration both basal and supplemental levels. The final target concentrations of Co, Cu, Mn, Se, and Zn were, respectively, 0.25, 13.7, 40.0, 0.3, and 40.0 mg/kg in the prepartum diet, and 0.25, 15.7, 40.0, 0.3, and 63.0 mg/kg in the postpartum diet. The STM group was supplemented with Co, Cu, Mn, and Zn sulfates and sodium selenite, while the OTM group was supplemented with Co, Cu, Mn, and Zn proteinates and selenized yeast. Treatments continued until 156 d in milk (DIM) and were assigned to individual cows using automatic feeding gates. Starting at 21 DIM, ultrasonography examinations of the ovaries were performed weekly to determine the presence of a corpus luteum and postpartum resumption of ovarian cyclicity. Cows were presynchronized with 2 injections of PGF2α at 42 and 56 DIM. Estrous behavior was monitored using electronic activity tags that indirectly measured walking activity. Cows detected in estrus after the second PGF2α were inseminated, and those not detected in estrus by 67 DIM were enrolled in a synchronization program. Cows that returned to estrus after artificial insemination (AI) were reinseminated. Pregnancy diagnosis was performed 33 d after AI, and nonpregnant cows were resynchronized. Transcript expression of interferon-stimulated genes in peripheral blood leukocytes was performed in a subgroup of cows (STM, n = 67; OTM, n = 73) on d 19 after AI. A different subgroup of cows (28 STM, 29 OTM) received uterine flushing 15 d after AI for recovery of conceptuses and uterine fluid for analyses of transcriptomics and metabolomics, respectively. In addition, dominant follicle diameter, luteal size and blood flow, and concentration of progesterone in plasma were measured on d 0, 7, and 15 relative to AI. After flushing, PGF2α was given and the dominant follicle was aspirated 2 d later to measure the concentration of trace minerals by mass spectrometry. Estrous behavior, size of the dominant follicle and corpus luteum, concentration of progesterone, time to pregnancy, and proportion of cows pregnant by 100 d of the breeding period did not differ between treatments. A greater proportion of cows supplemented with OTM had a corpus luteum detected before presynchronization (64.3 vs. 75.2%), and primiparous cows supplemented with OTM tended to resume cyclicity earlier than their STM counterparts. Cows supplemented with OTM had a greater concentration of Cu in follicular fluid than cows supplemented with STM (0.89 vs. 0.77 µg/mL, respectively). In pregnant multiparous cows, expression of receptor transporter protein 4 in peripheral blood leukocytes was 42% greater in the OTM group. Conceptuses of the 2 treatments had 589 differentially expressed transcripts, with many indicating advanced conceptus elongation and greater transcript expression of selenoproteins in the OTM group. In pregnant cows, 24 metabolites were more abundant in the uterine fluid of OTM, including spermidine, sucrose, and cholesterol. In conclusion, replacing STM with OTM caused modest improvements to resumption of ovarian cyclicity and important changes in preimplantation conceptus development, but it did not alter conception risk and pregnancy rate.

NIAS-Server 2.0: A versatile complementary tool for structural biology studies.

Increasing the repertoire of available complementary tools to advance the knowledge of protein structures is fundamental for structural biology. The Neighbors Influence of Amino Acids and Secondary Structures (NIAS) is a server that analyzes a protein's conformational preferences of amino acids. NIAS is based on the Angle Probability List, representing the normalized frequency of empirical conformational preferences, such as torsion angles, of different amino acid pairs and their corresponding secondary structure information, as available in the Protein Data Bank. In this work, we announce the updated NIAS server with the data comprising all structures deposited until Sep 2022, 7 years after the initial release. Unlike the original publication, which accounted for only studies conducted with X-ray crystallography, we added data from solid nuclear magnetic resonance (NMR), solution NMR, CullPDB, Electron Microscopy, and Electron Crystallography using multiple filtering parameters. We also provide examples of how NIAS can be applied as a complementary analysis tool for different structural biology works and what are its limitations.

Lavandula × intermedia-A Bastard Lavender or a Plant of Many Values? Part I. Biology and Chemical Composition of Lavandin.

This review article is the first in a series that provides an overview of the biology, chemistry, biological effects, and applications of Lavandula × intermedia (lavandin, LI). Despite its prevalence in cultivation and on the essential oil market, lavandin has received limited attention from the scientific community. Remarkably more attention is paid to Lavandula angustifolia (LA), which is commonly regarded as the superior lavender and has been extensively researched. Our goal is to provide a comprehensive review of LI, as none currently exists, and assess whether its inferior status is merited. In the first part, we outline the biological and chemical characteristics of the plant and compare it to the parent species. The chemical composition of lavandin oil is similar to that of LA but contains more terpenes, giving camphor notes that are less valued in perfumery. Nevertheless, lavandin has some advantages, including a higher essential oil yield, resulting in reduced production cost, and therefore, it is a preferred lavender crop for cultivation.

On the noxious black Amazonian scorpion, Tityus obscurus (Scorpiones, Buthidae): Taxonomic notes, biology, medical importance and envenoming treatment.

Tityus obscurus has caused mild, moderate and severe accidents of medical relevance in the eastern Brazilian Amazon and French Guiana. Tityus obscurus has sexual dimorphism although males and females have uniform black coloration. In the Amazon, one of the habitats of this scorpion is seasonally flooded forests (igapós and várzeas). However, most stings occur in terra firme forest areas (non-flooded region), where most rural communities are located. Adults and children stung by T. obscurus may experience an "electric shock" sensation for more than 30 h after the sting. Our data shows that people inhabiting remote forest areas, including rubber tappers, fishermen and indigenous people, with no access to anti-scorpion serum, use parts of native plants, such as seeds and leaves, against pain and vomiting caused by scorpion stings. Although there is a technical effort to produce and distribute antivenoms in the Amazon, many cases of scorpion stings are geographically unpredictable in this region, due to the lack of detailed knowledge of the natural distribution of these animals. In this manuscript, we compile information on the natural history of T. obscurus and the impact of its envenoming on human health. We identify the natural sites that host this scorpion in the Amazon, in order to warn about the risk of human envenoming. The use of specific antivenom serum is the recommended treatment for accidents involving venomous animals. However, atypical symptoms not neutralized by the available commercial antivenom are reported in the Amazon region. Facing this scenario, we present some challenges to the study of venomous animals in the Amazon rainforest and possible experimental bottlenecks and perspectives for establishing a method aimed at producing an efficient antivenom.

Biology and Roles in Diseases of Selenoprotein I Characterized by Ethanolamine Phosphotransferase Activity and Antioxidant Potential.

Selenoprotein I (SELENOI) has been demonstrated to be an ethanolamine phosphotransferase (EPT) characterized by a nonselenoenzymatic domain and to be involved in the main synthetic branch of phosphatidylethanolamine (PE) in the endoplasmic reticulum. Therefore, defects of SELENOI may affect the health status through the multiple functions of PE. On the other hand, selenium (Se) is covalently incorporated into SELENOI as selenocysteine (Sec) in its peptide, which forms a Sec-centered domain as in the other members of the selenoprotein family. Unlike other selenoproteins, Sec-containing SELENOI was formed at a later stage of animal evolution, and the high conservation of the structural domain for PE synthesis across a wide range of species suggests the importance of EPT activity in supporting the survival and evolution of organisms. A variety of factors, such as species characteristics (age and sex), diet and nutrition (dietary Se and fat intakes), SELENOI-specific properties (tissue distribution and rank in the selenoproteome), etc., synergistically regulate the expression of SELENOI in a tentatively unclear interaction. The N- and C-terminal domains confer 2 distinct biochemical functions to SELENOI, namely PE regulation and antioxidant potential, which may allow it to be involved in numerous physiological processes, including neurological diseases (especially hereditary spastic paraplegia), T cell activation, tumorigenesis, and adipocyte differentiation. In this review, we summarize advances in the biology and roles of SELENOI, shedding light on the precise regulation of SELENOI expression and PE homeostasis by dietary Se intake and pharmaceutical or transgenic approaches to modulate the corresponding pathological status.