Emerging concepts on the FGF23 regulation and activity.

Fibroblast growth factor 23 (FGF23) discovery has provided new insights into the regulation of Pi and Ca homeostasis. It is secreted by osteoblasts and osteocytes, and acts mainly in the kidney, parathyroid, heart, and bone. The aim of this review is to highlight the current knowledge on the factors modulating the synthesis of FGF23, the canonical and non-canonical signaling pathways of the hormone, the role of FGF23 in different pathophysiological conditions, and the anti-FGF23 therapy. This is a narrative review based on the search of PubMed database in the range of years 2000-2023 using the keywords local and systemic regulators of FGF23 synthesis, FGF23 receptors, canonical and non-canonical pathways, pathophysiological conditions and FGF23, and anti-FGF23 therapy, focusing the data on the molecular mechanisms. The regulation of FGF23 synthesis is complex and multifactorial. It is regulated by local factors and systemic regulators mainly involved in bone mineralization. The excessive FGF23 production is associated with different congenital diseases and with diseases occurring with a secondary high FGF23 production such as in chronic disease kidney and tumor-induced osteomalacia (TIO). The anti-FGF23 therapy appears to be useful to treat chromosome X-linked hypophosphatemia and TIO, but there are doubts about the handle of excessive FGF23 production in CKD. FGF23 biochemistry and pathophysiology are generating a plethora of knowledge to reduce FGF23 bioactivity at many levels that might be useful for future therapeutics of diseases associated with high-serum FGF23 levels.

Melatonin not only restores but also prevents the inhibition of the intestinal Ca(2+) absorption caused by glutathione depleting drugs.

We have previously demonstrated that melatonin (MEL) blocks the inhibition of the intestinal Ca(2+) absorption caused by menadione (MEN). The purpose of this study were to determine whether MEL not only restores but also prevents the intestinal Ca(2+) absorption inhibited either by MEN or BSO, two drugs that deplete glutathione (GSH) in different ways, and to analyze the mechanisms by which MEN and MEL alter the movement of Ca(2+) across the duodenum. To know this, chicks were divided into four groups: 1) controls, 2) MEN treated, 3) MEL treated, and 4) treated sequentially with MEN and MEL or with MEN and MEL at the same time. In a set of experiments, chicks treated with BSO or sequentially with BSO and MEL or with BSO and MEL at the same time were used. MEL not only restored but also prevented the inhibition of the chick intestinal Ca(2+) absorption produced by either MEN or BSO. MEN altered the protein expression of molecules involved in the transcellular as well as in the paracellular pathway of the intestinal Ca(2+) absorption. MEL restored partially both pathways through normalization of the O2(-) levels. The nitrergic system was not altered by any treatment. In conclusion, MEL prevents or restores the inhibition of the intestinal Ca(2+) absorption caused by different GSH depleting drugs. It might become one drug for the treatment of intestinal Ca(2+) absorption under oxidant conditions having the advantage of low or null side effects.

Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals.

The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains unclear. Pharmacological compounds such as menadione, dl-butionine-S,R-sulfoximine and ursodeoxycholic acid also modify intestinal Ca absorption as a consequence of altering the redox state of the epithelial cells. The paracellular pathway of intestinal Ca absorption is poorly known and is under present study in some laboratories. Another field that needs to be explored more intensively is the influence of the gene × diet interaction on intestinal Ca absorption. Health professionals should be aware of this knowledge in order to develop nutritional or medical strategies to stimulate the efficiency of intestinal Ca absorption and to prevent diseases.

Intestinal Ca2+ absorption revisited: A molecular and clinical approach.

Ca2+ has an important role in the maintenance of the skeleton and is involved in the main physiological processes. Its homeostasis is controlled by the intestine, kidney, bone and parathyroid glands. The intestinal Ca2+ absorption occurs mainly via the paracellular and the transcellular pathways. The proteins involved in both ways are regulated by calcitriol and other hormones as well as dietary factors. Fibroblast growth factor 23 (FGF-23) is a strong antagonist of vitamin D action. Part of the intestinal Ca2+ movement seems to be vitamin D independent. Intestinal Ca2+ absorption changes according to different physiological conditions. It is promoted under high Ca2+ demands such as growth, pregnancy, lactation, dietary Ca2+ deficiency and high physical activity. In contrast, the intestinal Ca2+ transport decreases with aging. Oxidative stress inhibits the intestinal Ca2+ absorption whereas the antioxidants counteract the effects of prooxidants leading to the normalization of this physiological process. Several pathologies such as celiac disease, inflammatory bowel diseases, Turner syndrome and others occur with inhibition of intestinal Ca2+ absorption, some hypercalciurias show Ca2+ hyperabsorption, most of these alterations are related to the vitamin D endocrine system. Further research work should be accomplished in order not only to know more molecular details but also to detect possible therapeutic targets to ameliorate or avoid the consequences of altered intestinal Ca2+ absorption.

Insecticidal activity of three essential oils against two new important soybean pests: Sternechus pinguis (Fabricius) and Rhyssomatus subtilis Fiedler (Coleoptera: Curculionidae) / Actividad insecticida de tres aceites esenciales contra dos nuevas plagas importantes de la soja: Sternechus pinguis (Fabricius) y Rhyssomatus subtilis Fiedler (Coleoptera: Curculionidae)

In the present study, the essential oils from Eucalyptus globulus Labill., Citrus sinensis L. Osbeck and Citrus limon L. were analysed by GC-MS (gas chromatography–mass spectrometry) and evaluated for their toxic effects on Sternechus subsignatus and Rhyssomatus subtilis, two important pest of soybean in South America. Contact toxicity assayed by impregnation on filter paper discs showed that these oils caused significant mortality of the test insects (100 percent of mortality at 5 uL/cm2). Eucalyptus oil (98.9 percent of 1,8-cineole) had the greatest contact toxicity (LD50 = 0.40 and 0.84 uL/cm2 for S. pinguis and R. subtilis, respectively), whereas orange (87.6 percent of limonene) and lemon oils (62.5 and 12.6 percent of limonenen and beta pinene, respectively) were less toxic (LD50 > 1 uL/cm2 for both insects). All the responses were found dose-dependent. Rhyssomatus subtilis was more resistant than Sternechus pinguis to the toxicity of the essential oils studied.

En el presente estudio se analizaron por CG-EM (cromatografía de gases-espectrometría de masas) los aceites esenciales de eucalipto (Eucalyptus globulus Labill.), naranja (Citrus sinensis L. Osbeck) y limón (Citrus limon L) y se evaluaron sus efectos tóxicos contra dos especies de plagas importantes para la soja en Sud América: Sternechus subsignatus y Rhyssomatus subtilis. La toxicidad por contacto, ensayada por discos de papel de filtro impregnados, mostró que estos aceites causaron una mortalidad significativa de los insectos testeados (100 por ciento de mortalidad a 5 uL/cm2). El aceite de eucalipto (98.9 por ciento de 1,8-cineol) presentó la mayor toxicidad por contacto (LD50 = 0.40 y 0.84 uL/cm2 para S. pinguis y R. subtilis, respectivamente), mientras que el aceite de naranja (87.6 por ciento de limoneno) y el de limón (62.5 y 12.6 por ciento de limoneno y beta pineno, respectivamente) fueron menos tóxicos (LD50 > 1 uL/cm2 para ambos insectos). Todas las respuestas fueron dosis dependiente. Rhyssomatus subtilis fue más resistente que Sternechus pinguis a la toxicidad de los aceites esenciales estudiados.